A Feasibility Trial Using Molecular-Guided Therapy for the Treatment of Patients With Relapsed and Refractory Childhood Cancer
Phase: NA
Conditions: Neuroblastoma, Medulloblastoma, Brain Tumors, Rare Tumors
Sponsor: Giselle Sholler

Clinical Protocol. NMTRC 008 
 
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Protocol NMTRC 008 
 
NCT01802567 
 
 
 
A Feasibility Trial using Molecular-Guided Therapy for the Treatment of Patients with 
Relapsed and Refractory Childhood Cancer 
 
 
 
 
 
 
Version 2.0    June 12, 2013  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Clinical Protocol. NMTRC 008 
 
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Contact Information: 
 
STUDY CHAIR: 
 
Giselle Sholler, MD 
NMTRC Chair 
100 Michigan Avenue NE  MC 272         
Grand Rapids, MI 49503 
Tel:  (616) 267-0332  
Fax: 616-391-2785 
giselle.sholler@helendevoschildrens.org 
 
Study Arms: 
 
Neuroblastoma Study Chair:  
 
Giselle Sholler, MD 
NMTRC Chair 
100 Michigan Avenue NE  MC 272         
Grand Rapids, MI 49503 
Tel:  (616) 267-0332   
Fax: 616-391-2785 
giselle.sholler@helendevoschildrens.org 
 
Neuroblastoma Study Vice Chair:   
 
Nehal Parikh, MD 
 
 
 
 
Assistant Professor of Pediatrics  
 
Connecticut Children's Medical Center 
 
Division of Hematology / Oncology 2J 
282 Washington Street 
Hartford, CT 06106 
Tel: 860-545-9630 
Fax: 860-545-9622 
Nparikh@ccmckids.org 
 
Brain Tumor Chair:   
 
 
Amy Lee Bredleau, MD 
Director, Pediatric Brain Tumor Program 
Assistant Professor, Sullivan Scholar 
Medical University of South Carolina 
135 Rutledge Avenue, MSC 558 
Charleston, SC 29425 
Phone: 843-876-2872 
Fax: 843-792-8912 
bredlau@musc.edu 
 
Brain Tumor Vice Chair: 
 
 
Don Eslin, MD  
 
 
 
MDACCO 
 
 
 
 
Pediatric Hematology/Oncology 
92 West Miller Street, MP 318 
Orlando, FL 32806 
 
 
 
 
 
 
Tel: 321-841-8588 
Don.Eslin@orlandohealth.com 

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Rare Tumor Chair:  
 
 
 
Jacqueline Kraveka, DO 
 
 
Assistant Professor of Pediatrics  
 
 
Medical University of South Carolina 
 
135 Rutledge Avenue, Room 480 
Division of Pediatric Hematology-Oncology 
MSC 558 
Charleston, SC 29425 
Tel: 843-792-2957 
Fax: 843-792-8912 
kravekjm@musc.edu 
 
 
 
Rare Tumor Vice Chairs:  
 
 
Melinda Merchant, PhD, MD 
 
 
Pediatric Oncology Branch 
 
 
National Cancer Institute 
10 Center Drive Bldg 10 Room 1W-3952 
Bethesda, Maryland 20892 
Tel: 301.443.7955 
merchanm@mail.nih.gov 
 
Kathleen A. Neville, M.D., M.S. 
 
Children's Mercy Hospitals and Clinics 
Divisions of Pediatric Clinical Pharmacology  
and Pediatric Hematology/Oncology 
2401 Gillham Road 
Kansas City, MO 64108 
kaneville@cmh.edu 
 
 
 
 
Safety Officer:  
 
 
 
Dr. Timothy Triche 
Department of Pathology and Laboratory 
Medicine 
Children's Hospital Los Angeles 
4650 Sunset Blvd., Mailstop 133 
Los Angeles, CA 90027 
Ph: 323-361-8898 
Fax: 323-361-4945  
triche@usc.edu 
 
 
 
 
 
 
 

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STUDY COMMITTEE MEMBERS: 
 
 
Genevieve Bergendahl, RN 
Clinical Program Director 
NMTRC 
100 Michigan Avenue NE  MC 272         
Grand Rapids, MI 49503 
 
Tel:  (616) 267-0335 
Fax: 616-391-2785 
E-Mail:  
Genevieve.bergendahl@helendevoschildrens.or
g  
 
 
Alyssa VanderWerff 
Clinical Program Coordinator 
NMTRC 
100 Michigan Avenue NE  MC 272         
Grand Rapids, MI 49503 
 
Tel:  (616) 267-0327  
Fax: 616-391-2785 
E-Mail:  
Alyssa.VanderWerff@helendevoschildrens.org  
 
Emily Arndt 
Clinical Project Coordinator 
NMTRC 
100 Michigan Avenue NE  MC 272         
Grand Rapids, MI 49503 
 
Tel:  (616) 267-0326  
Fax: 616-391-2785 
E-Mail:  
emily.arndt@helendevoschildrens.org  
Akshita Dutta, MS 
Computational Biologist 
NMTRC 
100 Michigan Avenue NE  MC 272         
Grand Rapids, MI 49503 
 
Tel:  (616) 267-0309   
Fax: 616-391-2785 
E-Mail:  
Akshita.dutta@helendevoschildrens.org  
William Ferguson, MD  
 
 
Pediatric Hematology-Oncology 
 
Cardinal Glennon Children’s Medical Ctr  
Saint Louis University School of Medicine 
1465 S. Grand Blvd. 
St. Louis, MO 
Tel:  
(314) 577-5638 
Fax:  
(314) 268-4081 
fergusws@slu.edu 
 
 
William Roberts, MD 
 
 
 
Pediatric Hematology/Oncology  
 
Rady Children's Hospital San Diego  
 
3020 Children’s Way MC5035 
San Diego, CA 92123-4282 
 
Tel:  
(858) 966-5811 
Fax:  
(858) 966-8035 
wroberts@chsd.org 
 
Don Eslin, MD  
 
MDACCO 
 
 
 
 
Pediatric Hematology/Oncology 
92 West Miller Street, MP 318 
Orlando, FL 32806 
Tel: 321-841-8588 
Don.Eslin@orlandohealth.com 
 
 

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Jacqueline Kraveka, DO 
 
 
Assistant Professor of Pediatrics  
 
Medical University of South Carolina 
 
Division of Pediatric Hematology-Oncology 
135 Rutledge Avenue, Room 480 
MSC 558 
Charleston, SC 29425 
 
Tel: 843-792-2957 
Fax: 843-792-8912 
kravekjm@musc.edu 
 
Joel Kaplan, DO, MPH  
 
 
Levine Children’s Hospital 
 
 
1000 Blythe Blvd 
 
 
 
Charlotte, NC 28203 
 
Tel: 704-381-9900 
Fax: 704-381-9901 
Joel.Kaplan@carolinashealthcare.org 
 
Deanna Mitchell, MD  
 
 
Michigan State University 
 
 
Helen DeVos Children’s Hospital 
100 Michigan NE 
Grand Rapids, MI 49503 
 
Tel: 616-391-2086 
Deanna.Mitchell@devoschildrens.org 
 
Nehal Parikh, MD 
 
 
 
Assistant Professor of Pediatrics  
 
Connecticut Children's Medical Center  
Division of Hematology / Oncology 2J 
282 Washington Street 
Hartford, CT 06106 
 
 
Tel: 860-545-9630 
Fax: 860-545-9622 
Nparikh@ccmckids.org 
 
 
Kathleen A. Neville, M.D., M.S. 
 
Children's Mercy Hospitals and Clinics 
Divisions of Pediatric Clinical Pharmacology  
and Pediatric Hematology/Oncology 
2401 Gillham Road 
Kansas City, MO 64108 
 
kaneville@cmh.edu 
 
Randal K. Wada, MD 
Associate Professor of Pediatrics and Nursing 
University of Hawaii 
Kapiolani Medical Center for Women and 
Children  
55 Merchant Street, 26th Floor 
Honolulu, HI 96813 
 
Office/Lab: (808) 586-2963 
tbear@cc.hawaii.edu 
  

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Melinda Merchant, PhD, MD 
Pediatric Oncology Branch 
National Cancer Institute 
10 Center Drive Bldg 10 Room 1W-3952 
Bethesda, Maryland 20892 
 
Tel: 301.443.7955 
merchanm@mail.nih.gov 
 
 
Francis Eshun, MD 
Center for Cancer and Blood Disorders 
Phoenix Children's Hospital 
1919 Thomas Road 
Phoenix, AZ 85016 
 
 
feshun@phoenixchildrens.com 
 
 
Valerie I. Brown, MD, PhD 
Assistant Professor of Pediatrics 
Division of Pediatric Oncology/Hematology 
Leader, Translational Biology 
Monroe Carrell Jr. Children’s Hospital at 
Vanderbilt Vanderbilt-Ingram Cancer Center 
397 Preston Research Building 
2220 Pierce Ave 
Nashville, TN 37232 
 
Phone: 615-875-6129 
Fax: 615-936-1767 
Email: valerie.brown@vanderbilt.edu 
 
 
Sharon K Lockhart, MD 
COG Principal Investigator 
Clinical Research Director,  
Dell Children's Blood and Cancer Center 
1301 Barbara Jordan Blvd, Ste 401 
Austin,  Texas   78723 
 
512-628-1900    office 
512-656-1801    cell 
512-628-1901    fax 
slockhart@sfcaustin.com 
 
Mark Fluchel, MD 
Primary Children's Hospital 
Division of Pediatric Hematology/Oncology 
100 North Mario Capecchi Drive, 4th Floor 
Salt Lake City, UT 84113 
 
Phone: 801-662-4700 
Fax: 801-662-4705 
email: mark.fluchel@imail.org 
 
Takamaru Ashikaga, Ph.D. 
 
 
Medical Biostatistics  
 
 
 
& Bioinformatics Facility 
 
 
UVM College of Medicine 
27 Hills Building 
105 Carrigan Drive 
Burlington, VT 05405 
 
Tel: 
(802)656-2526 
Fax (802)656-0632 
Takamaru.Ashikaga@uvm.edu 
 
 

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Jeffrey Bond, PhD 
 
 
 
Vermont Cancer Center  
 
 
UVM College of Medicine 
Given E-315 
89 Beaumont Avenue 
Burlington, VT 05405 
 
Tel:  
(802) 656-4608 
jeffrey.bond@uvm.edu 
 
Gina K. Hanna, PharmD 
Hematology Oncology/Investigational Drugs  
Clinical Pharmacy Specialist 
Nemours Children's Hospital 
13535 Nemours Parkway 
Orlando, Florida 32827 
 
Tel: 407.567.4815 
ghanna@nemours.org 
 
Stacy Epstein, Pharm.D., BCOP  
 
Clinical Pharmacy Specialist,   
 
Pediatric Blood and Marrow Transplantation 
Carolinas Medical Center 
Levine Children's Hospital 
1000 Blythe Boulevard 
Charlotte, North Carolina 28203 
 
Tel: 704-381-7173 
Fax: 704-381-7171 
Stacy.Epstein@carolinashealthcare.org 
Karen Gradischer 
 
 
 
Pharmacist 
 
 
 
 
Connecticut Children’s Hospital 
282 Washington Street 
Hartford, CT 06106 
 
Tel:  (860) 545-9935 
Kgradis@ccmckids.org 
 
Amy Lee Bredleau, MD 
Director, Pediatric Brain Tumor Program 
Assistant Professor, Sullivan Scholar 
Medical University of South Carolina 
135 Rutledge Avenue, MSC 558 
Charleston, SC 29425 
Phone: 843-876-2872 
Fax: 843-792-8912 
Jeff Trent 
Translational Genomics Research Institute 
(TGen) President and Research Director 
445 N 5th Street 
Phoenix, AZ 85004 
602-343-8419  
 jtrent@tgen.org 
            
Matt Huntelman 
Translational Genomics Research Institute 
(TGen) Associate Professor, Neurogenomics 
Division 
445 N 5th Street 
Phoenix, AZ 85004 
602-343-8730      
mhuentelman@tgen.org 
 

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Spyro Mousses PhD 
Vice President, Office for Innovation 
Professor & Director, Center for 
BioIntelligence Translational Genomics 
Research Institute (TGen) 
445 N. 5th Street, Suite 600 
Phoenix, AZ 85004 
 
602-343-8444  (O) 
602-653-5512 (M) 
602-343-8457  (F) 
smousses@tgen.org 
 
John Carpten 
Translational Genomics Research Institute 
(TGen) Deputy Director of Basic Science 
445 N 5th Street 
Phoenix, AZ 85004 
602-343-8819  
jcarpten@tgen.org 
                                               
Jeff Keifer 
Translational Genomics Research Institute 
(TGen) Research Associate Professor 
445 N 5th Street 
Phoenix, AZ 85004 
602-343-8667  
jkiefer@tgen.org 
Jason Corneveaux 
Translational Genomics Research Institute 
(TGen) Bioinformatician II 
445 N 5th Street 
Phoenix, AZ 85004 
602-343-8714 
 jcorneveaux@tgen.org 
  
 
 
 

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INVESTIGATOR SIGNATURE SHEET 
 
I have read the attached protocol amendment and agree that it contains all the necessary details 
for performing the study. 
 
I will provide copies of the amended protocol and of the preclinical and clinical information on 
the test article, which was furnished to me by the Sponsor, to all members of the study team 
responsible to me who participate in the study.  I will discuss this material with them to assure 
that they are fully informed regarding the test article and the conduct of the study. 
 
Once the protocol has been approved by the Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC), I will not modify this protocol without obtaining the prior approval of the 
Sponsor and of the IRB/IEC.  I will submit the protocol modifications and/or any informed 
consent form (ICF) modifications to the Sponsor and the IRB/IEC, and approval will be obtained 
before any modifications are implemented. 
 
I understand the protocol and will work according to it, the principles of Good Clinical Practice 
(GCP) [current International Conference of Harmonization (ICH) guidelines], and the Declaration 
of Helsinki (1964) including all amendments up to and including the Scotland revision (2000) and 
notes of clarification added in 2002 and 2004. 
 
 
 
 
 
Investigator's Signature 
 
Date 
 
 
 
Investigator’s Printed Name 
 
 
 
 
 
Investigational Site Name 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
Contact Information: ________________________________________________________ 2 
TABLE OF CONTENTS ____________________________________________________ 10 
PROTOCOL SYNOPSIS ___________________________________________________ 13 
TABLE OF PROCEDURES AND ASSESSMENTS _____________________________ 17 
 
1 
Background ______________________________________________________ 18 
1.1 Study Disease ________________________________________________ 18 
1.2 Rationale____________________________________________________ 18 
 
2 
STUDY OBJECTIVES _____________________________________________ 32 
2.1 Primary Objectives ____________________________________________ 32 
2.2 Secondary Objectives __________________________________________ 32 
 
3 
STUDY DESIGN __________________________________________________ 32 
3.1 Subject Enrollment and Sample Procurement and Data Processing ____ 32 
3.2 RNA Microarray Analysis ______________________________________ 33 
3.3 DNA Mutation Panel __________________________________________ 33 
3.4 Data Analysis and Predictive Methodologies _______________________ 33 
3.6 Safety Evaluations ____________________________________________ 40 
3.7 Efficacy Evaluations __________________________________________ 41 
3.8 Biological Studies _____________________________________________ 41 
  
4 
SUBJECT SELECTION ____________________________________________ 41 
4.1 Inclusion Criteria _____________________________________________ 41 
4.2 Exclusion Criteria ____________________________________________ 42 
 
5 
STUDY PROCEDURES AND ASSESSMENTS _________________________ 42 
5.1 Enrollment of Subjects_________________________________________ 42 
5.2 Screening ___________________________________________________ 43 
5.3 Study Procedures/Study Interventions ____________________________ 44 
 
 

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6 
Protocol Drugs ____________________________________________________ 47 
 
7 
Efficacy Assessments _______________________________________________ 49 
7.1 Tumor Assessments/Scans ______________________________________ 49 
7.2 Scan Submission: _____________________________________________ 49 
7.3 Response Criteria _____________________________________________ 49 
 
8 
Sample Size Justification ____________________________________________ 51 
 
9 
Laboratory Evaluations _____________________________________________ 52 
9.1 Specimens to be Collected, Schedule and Amount ___________________ 52 
9.2 Tumor collection and correlative biology studies. ___________________ 52 
9.3 Detailed Procedure For Sending Subject Samples: __________________ 53 
9.4 Correlative Biology Studies _____________________________________ 58 
9.5 Storage _____________________________________________________ 58 
9.6 Plan for Communication of Samples and Data _____________________ 59 
9.7 Plan for Communication of Collaborating Sites ____________________ 60 
 
10 ADVERSE EVENT REPORTING ____________________________________ 60 
 
11 SUBJECT WITHDRAWAL AND TRIAL DISCONTINUATION ___________ 64 
11.1 Criteria for Subject Off-Therapy ________________________________ 64 
11.2 Criteria for Subject Off-Study __________________________________ 64 
11.3 Trial Discontinuation _________________________________________ 64 
 
12 DATA ANALYSIS _________________________________________________ 64 
12.1 Data Quality Assurance _______________________________________ 64 
12.2 Data Safety Monitoring Board (DSMB) __________________________ 65 
12.3 Process and Feasibility Analysis ________________________________ 65 
12.4 Secondary Data Analysis ______________________________________ 65 
 
 
 

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13 ADMINISTRATIVE PROCEDURES _________________________________ 65 
13.1 Subject Informed Consent _____________________________________ 65 
13.2 Ethical Conduct of the Study and IRB/IEC Approval _______________ 66 
13.3 Monitoring _________________________________________________ 66 
13.4 Pre-Study Documentation _____________________________________ 67 
13.5 Confidentiality ______________________________________________ 67 
13.6 Source Documents ___________________________________________ 67 
13.7 Record Retention ____________________________________________ 68 
 
 
References ________________________________________________________________ 69 
 
Appendix I: Performance Status/Scores _______________________________________ 73 
 
Appendix II: Biology Studies Collection and Shipping forms ______________________ 74 
 
Appendix III: Pharmacopeia Library _________________________________________ 76 
 
Appendix IV: Intervention Insights Whole Body Reference Set ___________________ 266 
 
Appendix V: OncInsights Method Summary Diagram __________________________ 268 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PROTOCOL SYNOPSIS 
PROTOCOL TITLE 
A Feasibility Trial using Molecular-guided therapy for the treatment of 
patients with relapsed and refractory childhood cancers 
PROTOCOL NUMBER 
NMTRC 008 
PHASE OF DEVELOPMENT Feasibility 
OBJECTIVES 
Primary 
Determine feasibility of using tumor samples to assess genomic mRNA 
expression arrays and DNA Mutation Panels using predictive modeling 
to 
make 
real-time 
treatment 
decisions 
for 
children 
with 
relapsed/refractory cancers. 
 
Secondary 
• To continue to evaluate the safety of allowing a molecular tumor 
board to determine individualized treatment plans 
• To determine the activity of treatments chosen based on: 
• 
Overall response rate (ORR)  
• 
Progression free survival (PFS)  
•  (Voluntary) 
To 
explore 
the 
relationship 
between 
tumor 
phenotype/genotype and response by permitting use of tumor tissue 
in a correlative biologic study 
• To compare PFS interval to PFS intervals of previous 
chemotherapy regimens since relapse for each subject. 
STUDY DESIGN 
A prospective open label, multicenter study to evaluate efficacy of 
molecularly guided therapy in patients with relapsed or refractory 
childhood cancers 
 
A total of 48 evaluable subjects with childhood cancer that are 
refractory to or have relapsed on conventional therapy will be treated 
with molecular guided therapy.  
 
Subjects will be evaluated in 3 strata: 
• 
Stratum 1: 16 subjects with refractory/relapsed neuroblastoma 
• 
Stratum 2: 16 subjects with relapsed or refractory brain tumors 
Stratum 3: 16 subjects with refractory or relapsed rare tumors 
 
Guided therapy will allow the use of any therapeutic combination (up 
to 4 agents) provided it includes medications contained in the study 
report. All subjects will be followed for survival, disease response, 
progression and safety.  All subjects will be treated according to the 
discretion of the treating oncologist and study committee (minimum 3 
oncologists and one pharmacist). Extent of disease will be measured 
and assessed for changes throughout the course of the study.   
 
 

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ELIGIBILITY 
Inclusion Criteria 
1. Subjects must have histologically proven neuroblastoma, brain 
tumor, or rare tumor and confirmation of refractory or recurrent 
disease with histologic confirmation at diagnosis or at the time of 
recurrence/progression  
2. Subjects must be age >12 months at enrollment 
3. Subjects must be age  ≤ 21 years at initial diagnosis  
4. Subjects must have measurable disease as demonstrated by 
residual abnormal tissue at a primary or metastatic site measuring 
more than 1 cm in any dimension by standardized imaging (CT or 
MRI); tumor must be accessible for biopsy. Subjects with bone 
marrow only disease expected to be >75% tumor are eligible to 
enroll. 
5. Current disease state must be one for which there is currently no 
known curative therapy   
6. Lansky or Karnofsky Score must be more than 50 
7. Subjects without bone marrow metastases must have an ANC > 
750/μl. 
8. Adequate liver function must be demonstrated, defined as: 
a. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age 
AND 
b.  ALT (SGPT) < 10 x upper limit of normal (ULN) for age 
9. A negative serum pregnancy test is required for female 
participants of child bearing potential (≥13 years of age or after 
onset of menses) 
10. Both male and female post-pubertal study subjects need to agree 
to use one of the more effective birth control methods during 
treatment and for six months after treatment is stopped. These 
methods include total abstinence (no sex), oral contraceptives 
(“the pill”), an intrauterine device (IUD), levonorgestrol implants 
(Norplant), or medroxyprogesterone acetate injections (Depo-
provera shots). If one of these cannot be used, contraceptive foam 
with a condom is recommended. 
11. Informed Consent: All subjects and/or legal guardians must sign 
informed written consent. Assent, when appropriate, will be 
obtained according to institutional guidelines 
Exclusion Criteria 
1. Subjects who have received any cytotoxic chemotherapy within 
the last 7 days prior to enrollment and 14 days prior to study 
treatment start date.  
2. Subjects who have received any radiotherapy to the primary 
sample site within the last 14 days (radiation may be included in 
treatment decision after biopsy). 
3. Subjects receiving anti-tumor therapy for their disease or any 
investigational drug concurrently. 

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4. Subjects with serious infection or a life-threatening illness 
(unrelated to tumor) that is > Grade 2 (NCI CTCAE V4.0), or 
active, serious infections requiring parenteral antibiotic therapy.  
5. Subjects 
with 
any 
other 
medical 
condition, 
including 
malabsorption syndromes, mental illness or substance abuse, 
deemed by the Investigator to be likely to interfere with the 
interpretation of the results or which would interfere with a 
subject’s ability to sign or the legal guardian’s ability to sign the 
informed consent, and subject’s ability to cooperate and 
participate in the study  
 
Additional criteria: 
Subjects willing to participate in the correlative biologic studies will 
sign an additional consent form to provide tumor tissue. 
ESTIMATED NUMBER OF 
PATIENTS/GEOGRAPHIC 
REGIONS 
48 evaluable (53-59 total) relapsed/refractory pediatric cancer patients- 
16 neuroblastoma tumors, 16 brain tumors, and 16 rare tumors.  
Patients will enroll at Arnold Palmer Children’s Hospital (MD 
Anderson Cancer Center Orlando) ,St. Louis University/Cardinal 
Glennon Children's Medical Center, Helen DeVos Children’s Hospital, 
Levine Children’s Hospital, Connecticut Children's Medical Center, 
Mercy Children’s Hospital, Rady Children’s Hospital of San Diego, 
Medical University of South Carolina, Monroe Carrell Jr. Children’s 
Hospital at Vanderbilt, Phoenix Children's Hospital, Primary 
Children's Hospital, Kapiolani Medical Center for Women and 
Children, and at Dell Children’s Hospital. 
LENGTH OF STUDY 
Accrual to this study is estimated to be approximately 2 years. 
 
STUDY ASSESSMENTS 
Refer to Table of Assessments for timing of study procedures. 
CRITERIA FOR 
EVALUATION 
Feasibility Measures: Primary objective 
The definition of feasibility for this study will include: “Enrollment 
onto study, RNA expression profile completed, DNA Mutation 
Panel completed, genomic analysis and report generation, tumor 
board held with treatment decision, treatment review completed 
and start of treatment by 21 days post biopsy/surgical resection 
date, and then completion of 1 cycle of therapy.”  
Safety Measures: Secondary objectives 
• Safety analysis will be conducted on all subjects who have received 
at least one dose of therapy, and will include the frequency of all 
reported adverse events and laboratory abnormalities as well as 
frequency of dose interruptions, dose reductions and treatment 
discontinuation. 

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Efficacy Measures: Secondary objectives 
• Response: 
 To determine the overall response rate (ORR) by the presence of 
radiologically assessable disease by cross-sectional CT or MRI 
imaging and/or by MIBG or PET scans.  
 Duration of response, defined as the period of time from when 
measurement criteria are met for complete response (CR) or 
partial response (PR), whichever is first recorded, until the first 
date that recurrent or progressive disease (PD) is objectively 
documented (taking as reference for PD the smallest 
measurements recorded since the treatment started) 
 The assessment of response will include the initial measurable 
targets and will be performed after cycle 2, then after every other 
cycle.  
• A subject will be defined as a responder if CR/PR is observed at 
any time of the treatment  
• Clinical response will be seen if stable disease and decrease in 
tumor markers by ≥ 50% or CR of bone marrow.  
• Time to progression, defined as the period from the start of the 
treatment until the criteria for progression are met taking as 
reference the screening measurements 
STATISTICS/SAMPLE SIZE 
ESTIMATE 
48 evaluable subjects 
 
 
 
 
 

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TABLE OF PROCEDURES AND ASSESSMENTS 
 
Procedure 
Pre-
Study 
Cycle 
1 
Day 1 
Cycle 
1 
Day 8 
Cycle 
1 
Day 
15 
Cycle 1 
Day 22 (if 
applicable) 
Subsequent 
Cycles 
Day 1 
Off 
Therapy/ 
30 Day 
Follow-up 
Informed consent 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
Concurrent meds 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
X 
X 
X 
X 
X 
X 
X 
Vital signs 
X 
X 
 
X 
 
X 
X 
Height 
X 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
X 
X 
Karnofsky or Lansky 
play score 
X 
X 
 
X 
 
X 
X 
CBC w/diff,  
X 
X 
X 
X 
X 
X 
X 
Serum chemistry * 
X 
X 
 
X 
 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
Urine catecholamines 
(NB only) or  
other tumor marker (as 
available) 
X 
X 
 
 
 
X 
X 
surgical resection &/or 
diagnostic biopsy 
X 
 
MRI or CT 
X 
Radiologic measurements will be performed every 8 weeks or every 
other cycle (whichever occurs first) 
MIBG/PET (NB only) 
X 
Bone Marrow (NB or 
any subject suspected 
to have BM disease ) ^ 
X 
Should be repeated every 8 weeks or every other cycle (whichever 
occurs first) if positive at study entry 
B-HCG 
X 
  
  
  
  
  
  
EKG (as indicated) 
X 
  
  
  
  
  
  
*  Total bilirubin, BUN, creatinine, electrolytes, AST, ALT, LDH, Tumor Specific Marker  
(if available) 
 
^Standard of Care Bone Marrow. (Separate consent required for additional research samples. 
Collect per section 9.3.1.3) 
 
 
 
 
 
 
 
 

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1 
Background 
 
1.1 
Study Disease 
 
Relapsed or refractory neuroblastoma, brain tumors, and rare childhood tumors. 
 
1.2 
Rationale 
 
Lethality of Relapsed/Refractory Pediatric Cancers is an Unmet Clinical Need. 
 
Neuroblastoma 
Neuroblastoma is the most common extracranial solid tumor in children, with 700 new diagnoses 
projected for 2011. It accounts for 7% to 10% of childhood cancers [1, 2].  Whereas the prognosis 
for infants with neuroblastoma is generally good, currently only 30% of children diagnosed after 
12-15 months of age survive despite aggressive multimodal therapies [3, 4].  Even with high-dose 
chemotherapy (HDC) followed by hematopoietic stem cell transplantation (HSCT) and 
maintenance therapy with retinoic acid the 5-year event-free survival remains below 50% [5, 6].  
Long-term survival of patients who are treated with conventional therapies following relapse is 
<5%. As such, neuroblastoma accounts for 15% of all pediatric cancer deaths in the United States 
[7]. Consequently, the evaluation of new drugs is strongly needed in this disease.  
Recent evidence has established the genetic heterogeneity of the disease and revealed the 
existence of several major molecular subsets that collectively may provide prognostic value for 
future disease management [8] [9]. While the poor prognosis for older neuroblastoma patients 
underscores the need for new treatment strategies, the elucidation of specific biologic subsets of 
neuroblastoma suggests a way to improve disease management. The current standard-of-care 
treatments for relapsed neuroblastoma include a variety of Phase II or Phase I studies that 
generally have only modest response rates (10%-35%) [4]. Even in responding patients, tumors 
often go on to further rapid relapses and novel strategies to treat this patient population are 
urgently needed. There are currently few treatment options from which pediatric oncologists can 
select with any degree of confidence to improve the management of multiply recurrent 
neuroblastoma patients. The current strategy is to add salvage therapies based on the anecdotal 
experience of the treating physician, which often leads to drug-related toxicity but may or may 
not extend life. The identification of agents that target specific molecular pathways associated 
with the development and/or progression of neoplastic diseases holds promise. Improved 
approaches that identify in a more rational (data-driven) fashion combinations of existing agents 
that are likely to be effective should result in a survival benefit in the clinical setting, while 
avoiding the toxicity associated with agents that are unlikely to be beneficial. [10]. 
 
CNS Tumors 
CNS tumors are the most common solid tumors in children, with 3000-40 
00 new diagnoses each year. CNS tumors account for approximately 25-30% of all childhood 
cancers. Though many of these CNS tumors are quite treatable, the 5-year survival for pediatric 
CNS tumors is only 71%[11]. Patients who have relapsed and refractory CNS tumors are those 
most likely to succumb to their disease, in spite of aggressive chemotherapy and radiation, often 
followed by HSCT[12, 13]. Therefore, new treatment strategies are needed for control of CNS 
tumors. 

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There is a growing focus on treating CNS tumors based on the biology of the disease[14, 15] 
rather than with “one size fits all” therapy. Risk stratification in CNS tumors based on biology is 
increasingly understood to be a priority. For example, medulloblastoma has been broken into 4 
biologic categories with different genetic mutations and different clinical outcomes[16-18]. 
Similar to neuroblastoma, these differences in the biology and clinical outcome of patients with 
medulloblastoma suggest new strategies to improve disease management. The current standard-
of-care treatments for relapsed CNS tumors include Phase I and Phase II therapies that often have 
few, if any, responding patients[19, 20]. Again reflecting the challenges in neuroblastoma, 
responding patients with high grade CNS tumors often experience multiple relapses and are in 
dire need of novel treatment strategies. Improved approaches that can inform treatment regimens 
based on the biology of the disease could result in a survival benefit in this challenging patient 
population. 
 
Rare Cancers 
Although improvements in the past 40 years have led to markedly improved survival rates of 
approximately 80% overall for pediatric cancers, patients with relapsed, rare and advanced stage 
tumors still have a very poor prognosis. Soft tissue sarcomas account for ~ 7% of pediatric 
cancers, with 850-900 new cases annually in the United States [21].  Rhabdomyosarcoma, the 
most common soft tissue sarcoma in children and adolescents, affects nearly 350 children in the 
United States each year [21].  Patients with metastatic rhabdomyosarcoma have a poor prognosis 
with an overall survival rate of ~30% [22]. The non-rhabdomyosarcoma soft tissue sarcomas 
affect ~500 children each year.  Patients with metastatic non-rhabdomyosarcoma soft tissue 
sarcomas have long-term survival < 20% [23].  Malignant bone tumors (mainly Ewing’s Sarcoma 
and Osteosarcoma) account for 6% of childhood cancers, with ~400 cases of osteosarcoma and 
200 cases of Ewing’s Sarcoma diagnosed annually [21]. Patients with localized osteosarcoma, 
who have a poor response to pre-operative chemotherapy have a survival rate of around 50%, 
while patients with metastatic osteosarcoma or Ewing’s sarcoma disease at presentation, have a 
survival of < 20% [24, 25].  Renal Cancers account for ~6% of pediatric cancer diagnoses, with 
95% of cases being Wilms Tumor, which has a very favorable prognosis [21].  However, rare and 
high risk renal tumors such as metastatic anaplastic Wilms tumor, clear cell sarcoma of the 
kidney, renal cell carcinoma, and malignant rhabdoid tumor have an inferior outcome, with 
survival of < 20% [26, 27]. For all these patients survival remains poor, despite use of dose-
intensified multi-agent chemotherapy and stem cell transplantation. Therefore, new approaches 
such as targeted therapies are warranted. 
 
Molecular Networks as the Drug Target.  
It is now firmly established that cancer results from perturbations in the molecular networks 
within cellular systems that disturb the normal homeostatic state [28-30]. Fluctuations in these 
networks can result from genetic or epigenetic cellular events and/or changes in the molecular 
constitution of the tumor microenvironment, which collectively dictate the phenotype of the 
biological system. The molecular networks engaged during tumor development and/or 
progression are complex. Molecular networks have evolved to provide the ultimate level of 
cellular plasticity, allowing cells to adapt to or exploit extracellular cues within the local milieu 
[31]. The complexity of a tumor system is further exaggerated by the inherent genomic instability 
seen in many neoplasms, which leads to an accelerated micro-evolutionary process that results in 
further cellular and tumor sub-system heterogeneity [32, 33]. This variability combined with the 
adaptability of many molecular pathways provides a somewhat predictable and highly probable 
path to resistance for any given agent that targets a subset of cellular systems within a tumor’s 

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molecular and genetic repertoire [34]. A fundamental challenge in the area of targeted cancer 
treatment is how to identify optimal therapeutic combinations that can treat heterogeneous tumors 
that are both highly adaptive and that exhibit significant inter- and intra-patient variation [28, 35-
37]. Our proposal outlines an approach by which we can utilize our expanding knowledge of 
molecular networks and the mechanisms of action of a growing pharmacopeia [38, 39] in 
conjunction with standardized biomarker assessments to deliver targeted combinations of 
effective therapies to neuroblastoma patients. 
 
Practice and Promise of Biomarkers for Patient Treatment Planning. 
A panel of individual biomarkers has recently been identified that can be used in the clinical 
setting to identify neuroblastoma patients most likely to respond to a specific therapy. For 
example, activation of the ALK gene through sequence variation mutations has been identified in 
a subset of neuroblastoma patients, and small-molecule inhibition of the ALK-encoded receptor 
tyrosine kinase caused cytotoxicity in affected neuroblastoma cell lines [40]. Such studies, in 
conjunction with a large body of in vitro and in vivo data, have further demonstrated that the 
efficacy of specific treatment modalities is dependent upon the molecular constitution of the 
tumor, and that the observed variations in tumor response to current therapies is attributable in 
large part to disease heterogeneity at the molecular level.  
 
While individual biomarkers may be predictive of responses to specific therapies, especially in 
the context of front-line treatment, a different approach to the management of patients with 
refractory disease is needed in order to identify effective treatments from the catalog of available 
agents. Advances in informatics and molecular technologies, coupled with our expanding 
knowledge of molecular networks and mechanism of action of the existing pharmacopeia, 
provide a great opportunity in translational medicine to develop a model that more accurately 
predicts tumor response. The studies outlined in this proposal are a step in the development of 
personalized oncology, in which each patient is truly treated individually based upon the 
systematic molecular analysis of their disease. Our project is focused on testing the merits of a 
specific data-driven predictive method through which any number of drugs in our current 
knowledge base has a chance of being recommended, of these only the FDA approved drugs 
listed in Appendix III will be used. Although this novel approach to personalized therapeutics 
brings with it to the concern that toxicities that may arise from novel combinations of agents, it is 
strongly felt by the investigators that the logical interpretation of molecular data by a committee 
of highly qualified physicians and pharmacists in order to identify drug candidates for 
consideration in the treatment of a patient population with few alternative options is a worthwhile 
endeavor. The systematic biomarker-driven approach outlined in this proposal, by tailoring a 
combination of drugs targeting the specific molecular composition of a tumor—irrespective of 
tumor classification or anatomical origin— provides a feasible alternative to the conventional 
approach that targets specific organs or tissues without consideration of the underlying tumor 
biology. 
 
Validation of Gene Expression as a Predictive Biomarker. 
The determination of gene transcript abundance through gene expression profiling has been 
frequently exploited in biomarker research. The mRNA analyte provides an estimation of the 
dynamic molecular events within a biological specimen. Moreover, various technologies that 
permit gene expression profiling have provided a systematic and high-throughput means to assess 
multiple mRNA transcripts simultaneously within a biological sample on a genomic scale, and 
have created an abundance of empirical datasets across cohorts of moderately characterized 
biological specimens [41]. Within the field of cancer research, gene expression profiles derived 

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from human tumor specimens have been used to identify molecular subtypes associated with 
tumor cell behavior, patient outcome and response to a wide range of therapies [42]. For example, 
gene expression signatures have been utilized to create a connectivity map in which the genomic 
consequences of drug exposure can be aligned with de-regulated genes within a tumor specimen 
to identify compounds that may reverse the tumorigenic genotype [43]. Screening of a large 
number of potential therapeutic agents in a panel of cancer cell lines with a baseline gene 
expression profile has permitted the association between a gene expression signature and 
predicted response to various drugs [44, 45]. Thus, a wealth of publicly available genomic 
datasets and predictive methodologies coupled with increasing evidence demonstrating the utility 
of gene expression signatures as a valid biomarker argues for increased efforts towards 
implementing a more systematic approach to molecular-based theranostics in the prospective 
clinical setting. We propose to integrate the results of different predictive methodologies based 
upon the consistent input of tumor-derived gene expression data, to provide consolidated 
information to the treating physician regarding treatment options with predicted efficacy. The 
predictive methods under evaluation include the rudimentary analysis of expression of target 
genes, as well as the more sophisticated analysis of molecular network topology and signature 
based methods based upon empirical datasets. Throughout the project, we will seek to establish 
the potential predictive value of standardized gene expression data and the described 
methodologies for predicting efficacious agents for refractory or relapsed neuroblastoma patients 
and determine which, if any, of these individual predictive methodologies holds the most promise 
for further development as a diagnostic standard. Additionally, while beyond the scope of this 
specific proposal, the tumor resource created will also be used to assess the potential predictive 
value of emerging molecular technologies that assess other molecular aberrations associated with 
differential therapeutic response (such as single nucleotide polymorphisms, DNA sequencing, 
gene amplifications/deletions, gene promoter methylation, protein modifications, etc [28, 30]. 
 
 
Pivotal Pilot Study Highlights Feasibility of Predictive Methodologies. 
In conjunction with community hospitals and physician groups in West Michigan, the Van Andel 
Research Institute under the direction of Dr. Webb recently completed a proof-of-feasibility study 
in which a heterogeneous group of fifty late stage cancer patients were enrolled to determine the 
feasibility and potential impact of providing physician’s with molecular-based therapy predictions 
and to provide an early assessment of the first generation predictive methodologies. In this 
feasibility study, clinical investigators worked closely with Dr. Webb to coordinate a multi-
disciplinary team that included individuals from adult and pediatric oncology, surgery, 
interventional and non-interventional radiology, pathology, pharmacy, clinical research, statistics, 
bioinformatics, and clinical and basic science laboratories. 
 
Table 1 shows a sample of patients enrolled in this first pilot study, and highlights the patients 
whose physicians utilized the personalized report providing an early indication of the potential 
value of the information provided. In brief, 50 patients were consented to the study in which 
surgical tumor specimens excised as part of a standard of care diagnostic procedure were 
processed in a real-time fashion to obtain a gene expression profile from each qualified tumor 
specimen. Consistent with current practices, a series of essential quality control (QC) standards 
were implemented to ensure assay validity which included criteria regarding the proportion of 
viable tumor cells within surgical specimens, RNA quality, cDNA synthesis and amplification, 
GeneChip hybridization, data normalization and analysis. After obtaining a gene expression 
profile on the tumor specimen, researchers utilized the XB-BIS system to generate a standardize 
report for physicians to utilize in determining patient drug regimen. It is important to note that our 

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current procedures permit a < 3 week turnaround from receipt of an individual tumor sample to 
the generation of a standardized report predicting drug efficacy. Our ability to provide real time 
feedback in less than 3 weeks is critical to permit the consideration of the predicted therapies in 
the care of the individual patient, and is concomitant with the wash out period between the 
patient’s prior treatment and administration of a new regimen. 
 
Table I: Sample of patient feasibility assessments. 
 
 
While this first 50-patient study was designed to determine the feasibility of the overall approach 
in different tumor types and to establish the necessary logistical workflow between the multiple 
disciplines, some anecdotal signs of tumor response and physician-reported patient benefit were 
observed (Table 1). As the Table illustrates, useful data was generated on 39/50 patients.  Of 
these, 24 out of the 34 cases utilized the report information.  Treatment decisions were based on 
the reported data for 24 patients, and 9 patients experienced tumor responses (37.5% response 

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rate) determined through objective assessment of tumor burden (radiological imaging and/or 
biomarker endpoints, manuscript in preparation). While these findings remain anecdotal due to 
the uncontrolled nature of the study, they provide significant impetus to move ahead with the 
disease focused trial design outlined in this proposal. Moreover, these preliminary studies have 
demonstrated the feasibility of the approach in the real time prospective clinical setting. 
 
Use of Transcriptional Analysis to Assess Gene Target Expression. 
In the proof-of-feasibility study, the specific predictive methodologies were being developed and 
refined throughout, and led to the standardized methods outlined in this proposal. The most 
rudimentary method of transcriptional analysis relates to assessment of target gene expression. In 
some cases, the over-expression of a specific drug target at the transcriptional level is associated 
with efficacy of an inhibitor against the corresponding protein target; for example over-
expression of Her2 indicates use of trastuzumab in breast cancer [46]. Despite concerns over the 
discordance between transcript expression and protein target activity (which is partially addressed 
through development of our network topology method described below), the simple assessment 
of target transcript abundance showed early promise in the pilot study. For example, a complete 
response was observed in a female adolescent with acute lymphoblastic leukemia (ALL) 
following the administration of a multi-kinase inhibitor that was selected based upon a significant 
over-expression of one of the drugs known targets (Flt-3) at the transcriptional level (z-score 
>+10). Thus, while we now also incorporate a more sophisticated analytical method to infer 
target activation status based upon analysis of network topology (see below) and will also be 
testing the utility of well published signature-based methods for selecting drug candidates[43-45, 
47, 48] simple target gene expression remains a rational method for identification of drug 
candidates. The knowledge base utilizes the existing pharmacopeia’s postulated molecular 
mechanisms of action and contains molecular entities that are targeted by drugs, many of which 
are approved for human use. This includes several targets of particular relevance to 
neuroblastoma including VEGFA-VEGFR, TRK, mTOR, ALK, HDAC etc [8]. The 
transcriptional status of each of these targets is reported using the standardized z-score where the 
relative level of each target within an individual’s tumor is determined through a comparison with 
a whole body reference set. 
 
Novel Molecular Network Topology Analysis to Improve Utility of Targeted Pharmacopeia. 
A novel method developed in partnership with GeneGo over the past few years relates to the 
analysis of molecular network topology [49]. As stated above, the expression of a target gene 
does not necessarily equate to activation of the target protein. Nonetheless, we investigated the 
possibility of utilizing known protein-protein and protein-small molecule interactions within 
GeneGo’s MetaCore™ database (over 200,000 interactions) in conjunction with transcriptional 
data to infer key network targets that if modulated with a targeted agent, may disrupt the disease 
system(s) identified within each patient’s tumor. As with all methodologies in this proposal, 
tumor-derived transcriptional data (normalized to a reference set of normal whole body samples) 
provides the consistent input to the algorithm. This specific methodology was applied 
retrospectively to the data generated during the first 50-patient feasibility study and anecdotally 
corroborated the potential of this systematic approach for identifying key target hubs within 
perturbed molecular networks. For example, in the leukemic cells of the pediatric patient with 
ALL described above, Flt-3 was identified as a likely input point to an integrated transcriptional 
network. This patient responded well to a targeted therapy that inhibits multiple kinases including 
Flt-3. In an adult patient with metastatic non-small cell lung carcinoma, analysis of network 
topology highlighted Egfr as a likely input to a highly connected transcriptional network, and 
subsequent treatment with erlotinib showed some efficacy (patient exhibited a partial response). 

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This methodology has also been tested more systematically against specific public domain 
datasets. For example, Dr. Webb’s group applied the methodology to a public dataset derived 
from the transcriptional profiling of skin from psoriasis patients. They were quickly able to 
identify several key targets and some associated targeted agents using this approach, many of 
which have been validated in the psoriasis literature. Collectively, we believe that the approach to 
the identification and subsequent analysis of neuroblastoma networks outlined in this proposal 
provides an exciting tool for systematically selecting network-based targeted regimens for the 
treatment of refractory or relapsed neuroblastoma patients. The systematic and automated 
approach described in this proposal is readily applicable to uncovering high quality therapeutic 
targets, and holds great promise for developing network-based combinational treatment strategies 
for a wide range of diseases especially for diseases such as neuroblastoma which have a low 
survival rate and are in need of new therapies. [2, 30]. 
 
 
Methods to be used in generating this reports are;  Drug Target Expression Algorithm, Network 
Target Activity (Systems Biology Method, GeneGo); Drug Response Signatures Algorithm 
(Connectivity Map), and Drug Sensitivity Signatures Algorithm (PGSEA).  These are furthered 
explained in section 3. 
 
Reference Set:  Whole body bank of normal tissue gene expression levels are used as the 
reference set for the normalization calculations.  Whole body reference is chosen to provide a 
wide variance of gene expression for comparison in order to better identify signal from tumor 
tissue.  This reference set will also help to decrease risk for toxicity as it will not identify targets 
that are highly expressed in normal tissues.    
 
Normalization Calculations 
A z-score is calculated using the mean gene expression level from the reference set to the same 
gene's expression level from the patient's tumor.  A z-score is a quantitative measure of the 
number of standard deviations above or below the mean of the observed value (patient’s gene) in 
comparison to the same observed value (the same gene in the reference set).  Positive z-scores 
reflect the number of standard deviations that the observation being evaluated is above the mean 
(over-expressed) and conversely negative z-scores represent the number of standard deviations 
that the observation being evaluated is below the mean (under-expressed). 
 
Drug Knowledgebase 
The drug knowledgebase is comprised of publically available, peer-reviewed and clinically 
relevant pharmacological data.  Numerous sources contribute to the knowledgebase including 
GeneGo, DailyMed, DrugBank, UpToDate, Entrez Gene, Entrez Pubmed, PharmaGKB, 
MedTrust Online and MedTrack. 
 
 
Preclinical Model for Neuroblastoma Patients  
Neuroblastoma cells can be isolated from either tumor biopsies or the bone marrow of patients 
using flow cytometry panel (GD2, CD81, CD9, CD56, CD34, CD45) or ficoll gradient isolation 
[50]. The bone marrow cells have been sorted and mRNA isolated for expression arrays. The 
patient cells have been cultured in our lab resulting in both adherent neuroblastoma cells and 
neurospheres. These cells have been grown for drug testing in vitro and injected into mice for in 
vivo tumor formation. This will be an important correlative study to continue to use in 
comparison to clinical response in patients. 

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Analysis of OncInsight’s Drug Prediction Compared to Empirical Drug Sensitivity of SK-N-
AS and SH-SY5Y Neuroblastoma Cell Lines 
Total RNA preparations from each of SK-N-AS and SH-SY5Y from Dr. Khan’s laboratory were 
analyzed using Affymetrix’s HG-U133 Plus 2 platform.  Raw MAS5 data was converted using 
Intervention Insight’s whole body expression data, a collection of 45 different adult tissues 
supplied by Asterand. Dr. Khan’s laboratory supplied Intervention Insights with CEL file data 
from Affymetrix’s HG-U133 Plus 2 platform generated in their laboratory to be used as a 
comparator of cross-laboratory expression data.  An Intervention Insights, OncInsights report of 
predicted drugs was prepared exactly as described elsewhere in the protocol. 
 
Fifty-six compounds were tested at high and low concentrations in a cell growth assay for each of 
SK-N-AS and SH-SY5Y (determined as percent growth at 24 hrs post drug treatment)[51].  Of 
the fifty-six compounds tested, the OncInsights system could select up to eighteen drugs.  Of the 
eighteen drugs selectable, nine were selected (50%, selected either as sensitive or insensitive).  
Seven drugs were selected in the analysis of SK-N-AS and nine drugs were selected in the 
analysis of SH-SY5Y.  Thirty two overlaps were comparable [SK-N-AS high concentration (7); 
SK-N-AS low concentration (7); SH-SY5Y high concentration (9) and SH-SY5Y low 
concentration (9)]. For SK-N-AS, 79% agreement was observed and 21% disagreement was 
observed.  For SH-SY5Y, 61% agreement was observed and 39% disagreement was observed.  
Combined, OncInsights accurately predicted growth sensitivities for SK-N-AS and SH-SY5Y 
63% of the time. 
 
Analysis of OncInsight’s Drug Prediction Compared to PPTP drug sensitivity. 
The National Cancer Institute (NCI) has established the Pediatric Preclinical Testing Program 
(PPTP) for testing drugs against in vitro and in vivo childhood cancer models to aid in the 
prioritization of drugs considered for early phase pediatric clinical trials. Drugs tested in 
xenograft models and predicted to be effective were evaluated using the OncInsights report as a 
comparison. 
 
AZD2171 Response in Rhabdoid Kidney Tumor 
FGFR2 overexpression has been identified to affect a variety of bone, skin and cancer 
pathologies[52]. In this PPTP xenograft sample of a rhabdoid kidney tumor (KT-16), a complete 
response was shown when treating the tumor with AZD2171 (Recentin®). The mRNA from the 
xenograft KT-16 was analyzed using Affymetrix’s HG-U133 Plus 2 platform and converted using 
Intervention Insight’s whole body expression data.   The OncInsights platform using the Drug 
Target Expression Method identified AZD2171 as a potential therapeutic option, based on the 
overexpression of FGFR2 (Z=3.978) from this mouse xenograft.   

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Figure 1: (Left) A complete response (orange square) to the experimental agent, AZD2171, is 
shown in the PPTP Rhabdoid Kidney xenograft, KT-16. (Right). The Drug Target Expression 
Method identifies ADZ2171 as a potential therapy based on overexpression of FGFR2. 
 
 
Dasatinib Response in B-Cell ALL 
Several recent papers have demonstrated the effectiveness of dasatinib in the treatment of patients 
with ALL[53-55]. In this PPTP mouse xenograft of B-cell ALL (ALL-4), treatment with 
dasatinib resulted in a complete response. The mRNA from the xenograft  ALL-4 was analyzed 
using Affymetrix’s HG-U133 Plus 2 platform and converted using Intervention Insight’s whole 
body expression data.   The OncInsights platform showed that three of the seven targets of 
dasatinib were found to be activated in this tumor using the network-based Transcription Factor 
Activity Method.  
Figure 2: (Left) Dasatinib (BMS-354825) was shown to produce a complete response (orange 
square) in this mouse xenograft of B-cell ALL (ALL-4). Of the seven targets of dasatinib, three 
were found to be activated using our Transcription Factor Activity Method. 
 
 
 

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DNA mutation panel and use of Ion Torrent 
Spectrum Health Molecular Diagnostics offers a CLIA certified targeted next generation 
sequencing test utilizing multiplex PCR with ion semiconductor sequencing (The Ion 
AmpliSeq™ Cancer Hotspot Panel v2) designed to amplify 207 amplicons covering 
approximately 2,800 COSMIC mutations from 50 oncogenes and tumor suppressor genes. This 
includes the 739 COSMIC mutations from 46 genes in the first Ion AmpliSeq™ Cancer Panel 
along with added hotspot mutations from significant cancer genes. The test can provide important 
individual information regarding tumor development and progression, and a more reliable 
prediction of personalized cancer therapies. This Cancer Gene Mutation Panel is designed to 
target 739 mutations in the following 46 key cancer genes: ABL1, AKT1, ALK, APC, ATM, 
BRAF, CDH1, CDKN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, 
FGFR2, FGFR3, FLT3, GNAS, HNF1A, HRAS, IDH1, JAK2, JAK3, KDR, KIT, KRAS, MET, 
MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, 
SMAD4, SMARCB1, SMO, SRC, STK11, TP53, VHL, EZH2, GNA11, GNAQ, and IDH2. This 
mutation panel is designed to detect targeted mutations only. The 46 genes are not sequenced in 
their entirety. Mutations outside the targeted regions will not be detected. The limit of detection is 
5% at 500X coverage.  
 
This is a test currently available at centers such as Baylor College of Medicine as the “Cancer 
Gene Mutation Panel - Targeted Mutation Detection by Next Generation Sequencing”.   While it 
is currently available for patients, our study will examine the safety and predictive value for 
tumor boards of this test in pediatrics. 
 
A Pilot Trial Testing the Feasibility of using Molecular-Guided Therapy in Patients with 
Refractory or Recurrent Neuroblastoma. 
 
The primary objective of this pilot study was to evaluate the feasibility of using predictive 
modeling based on genome-wide mRNA expression profiles of neuroblastoma tumor biopsies to 
make real-time treatment decisions.  Feasibility was defined as the completion of the following in 
a two week time period: tumor biopsy, quality RNA extraction, mRNA U133 2+ Affymetrix gene 
chip hybridization, analysis utilizing a series of predictive methodologies, report generation, 
tumor board review with formulated treatment plan, and medical monitor review. Subjects were 
not treated on this study. There were 5 subjects enrolled between April-June 2010 with multiply 
relapsed or refractory neuroblastoma. Subjects had received between 2-13 previous relapsed 
therapies and were between 2-6.5 years post diagnosis. All subjects had soft tissue disease which 
was able to be biopsied. All biopsies were adequate by pathology evaluation (>75% viable tumor) 
and RNA quality (>6.5 RIN). Gene chips were completed in 3-7 days, report generation was 1-5 
days, tumor board was 1-3 days, medical monitor sign off was 1 day. The total time was 10-12 
days for all subjects. The tumor board which consisted of 4-10 pediatric oncologists from sites 
across the US and a pediatric oncology pharmacist was able to create individualized therapy 
regimens for all subjects. Correlative biology specimens were obtained and grown in culture. 
Mice xenografts of 3/5 subjects were established. Cultures and xenografts are able to be used for 
validation studies of predicted drug sensitivity. In conclusion it is feasible to obtain real-time 
genomic profiling for molecularly guided therapy for use in treatment decision making.  
 
 
 
 

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A Feasibility Trial using Molecular-Guided Therapy in Patients with Refractory or 
Recurrent Neuroblastoma. 
 
The primary objective of this feasibility study was to evaluate the feasibility and safety of using 
predictive modeling based on genome-wide mRNA expression profiles of neuroblastoma tumor 
biopsies to make real-time treatment decisions.  Feasibility was defined as “enrollment onto 
study, quality mRNA obtained, gene chip completed, tumor board held, medical monitor review 
and approval, start of treatment by 21 days post biopsy/surgical resection date, and completion of 
1 cycle of therapy.” There are 11 subjects enrolled to date with multiply relapsed or refractory 
neuroblastoma. Subjects were between 1-7 years post diagnosis. All subjects had soft tissue 
disease which was able to be biopsied. All biopsies were adequate by pathology evaluation 
(>75% viable tumor) and RNA quality (>6.5 RIN). 2 subjects were deemed ineligible due to 
tumor type after biopsy. Gene chips were completed in 3-8 days (95% CI: 3.8 – 6.8), report 
generation took 0-3 days (95% CI: 0.0 – 1.5), tumor board took 1-6 days (95% CI: 1.6 – 4.2), 
medical monitor sign off took 1-2 days (95% CI: 0.8 – 1.4). The total time from date of biopsy to 
tumor board was 6-11 days (95% CI: 7.5 – 10.2) for all subjects and 7-20 days to treatment (95% 
CI: 8.9 – 16.1). The tumor board which consisted of 4-15 pediatric oncologists from sites across 
the US and a pediatric oncology pharmacist was able to create individualized therapy regimens 
for all subjects. Correlative biology specimens were obtained and grown in culture. Mice 
xenograft establishment is ongoing. Cultures and xenografts are able to be used for validation 
studies of predicted drug sensitivity. In conclusion it is feasible to obtain real-time genomic 
profiling for molecularly guided therapy for use in treatment decision making.  
 
The study endpoint showing that 9/14 patients were feasible to enroll, biopsy, genomic analysis, 
tumor board review and patient treatment was met. All regimens were found to be safe by the 
medical monitor proving that the molecular tumor board was able to make safe decisions similar 
to hospital tumor boards making treatment decisions without molecular information on the 
patients. It was felt that the pharmacy review for evaluating drug-drug interactions and deciding 
on laboratory and safety testing was an important part of the tumor board (this is not usually 
present at hospital tumor boards) and will continue to be incorporated in this and future trials.   
All patients tolerated therapy well and were treated without any adverse events >grade 2 related 
to study drugs. 
 
 

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Neuroblastoma Gene Target Analysis Platform Reproducibility 
Activities 
Five core needle biopsies were processed for the reproducibility study: MGT 2, 3, 4, 7, and 8. 
One of these, MGT 4, was subsequently found to be a neuroendocrine carcinoma. Since five such 
samples are required, completion of the reproducibility study requires one additional patient.  
Background 
and 
Goal 
The 
Neuroblastoma 
Gene Target Analysis 
Platform 
(IDE 
# 
G100111) includes a 
process that, based on 
core needle biopsies 
of a neuroblastoma 
solid tumor, provides 
genome-wide 
expression 
profiles, 
comparative gene expression profiles based 
on a reference collection of normal tissues, 
and a set of drug therapies, each of which 
has a score (Figure 1). We proposed to study 
reproducibility of the IDE by applying it to 
triplicate samples obtained by dissecting 
each of five solid tumors. The primary goal 
of the reproducibility study is to evaluate the 
variation among sets of drug therapies 
associated with the same tumor. Secondary 
goals are 1) to compare the variation among 
sets of drug therapies from the same tumor 
with variation between tumors from distinct 
patients and 2) to evaluate variation 
associated with earlier steps in the process, 
in 
particular, 
expression 
profiles 
and 
comparative expression profiles (Figure 1). 
Design 
The design employed (Figure 2) was a 
hierarchical component that allows us to quantify variation within biopsies and to evaluate it 
within the context of the variation between biopsies as well as a cross-classification by GeneChip 
batch that allows us to evaluate batch effects. 
Methods 
Affymetrix GeneChip oligonucleotide array technology is used to obtain gene expression profiles, 
൛Eg|g ∈Gൟ, where G is the set of probe sets on the GeneChip. The OncInsights service calculates 
comparative expression profiles, ൛Zgൟ, from the sample mean and sample standard deviation, 
൛൫EഥgR, sgR൯ൟ, of a Reference collection of normal tissue expression profiles using Zg =
Eg−EഥgR
sgR .  
The OncInsights service uses comparative expression profiles to obtain a set of drug therapies, 
Dpr, for each patient, p, and replicate biopsy, r, as well as scores, ൛Sprdൟ, for each drug, d in Dpr. 
The reproducibility of the identification of a drug, d ∈Dpr, is defined as the proportion of other 
drug sets associated with the same patient that identify the drug  
 
Figure 2. Reproducibility study design. Triplicate 
patient biopsies allow us to quantify variation 
within biopsies and to evaluate it in the context of 
the variation between biopsies. Each of the three 
biopsy sections is processed to obtain cDNA. cDNA 
samples are split and processed in two batches, 
allowing us to evaluate variation associated with 
processing batch.  
 
Figure 1. The IDE identifies drug therapies based on a solid tumor 
biopsy. Expression profiles and comparative expression profiles are 
intermediate results. 

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Fprd =
1
หRpห−1
෍
H൫d ∈Dpr′൯
r′∈Rp,r′≠r
 
where H is an indicator function that equals 1 when its argument is true and 0 otherwise, Rp is the 
set of replicates, and หRpห is the size of Rp (3, the number of replicates). Fdpr = 1 when drug d is 
identified on all replicate lists and Fprd = 0 when it is not identified on any other list. We 
consider the average reproducibility associated with each patient, Fതp, that is, the average of Fprd 
over replicates and drugs,  
Fതp = ෍
1
หDprห෍Fprd
d∈Dpr
r
 
as well as the average reproducibility of drugs scoring above a threshold, Fത(S), that is, the 
average of Fdpr over patients, replicate drug lists, and drugs, conditional upon the drug achieving 
a minimum score 
Fത(S) = 1
|P| ෍෍
1
หd:Sprd > Sห
෍
Fprd
d:Sdpr>S
r
p
 
We note that a method that uniformly identifies every drug would not be an acceptable method 
yet would exhibit perfect reproducibility. We therefore evaluate the variation among drug lists 
associated with the same patient in the context of the variation among drug lists from different 
patients. Methods developed by Gower, Anderson, and their coworkers [56-58] and the Jaccard 
distance allow us to use the framework familiar from univariate ANOVA. More precisely, these 
methods allow us to test the null hypothesis that the variation among sets lists associated with 
different patients can be accounted for by the variation among drug sets associated with the same 
patient as well as to partition the variation into components so that their magnitudes can be 
compared. 
 
 

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Results 
Expression profiles 
Distance-based 
nonparametric 
multivariate 
analysis of variance [57, 58] allowed us to reject the null hypothesis that variation between 
biopsies can be accounted for by the variation within biopsies (p=0.001). That the variation 
among expression profiles associated with the same biopsy is small compared with the variation 
between expression profiles associated with different biopsies is apparent from Principal 
Component Analysis (Figure 3).  
 
Sets of drug therapies  
Similarly, the variation among drug sets associated with the same biopsy is small compared with 
the variation among drug lists associated with different biopsies (p=0.001). The reproducibility 
averaged over patients, replicates, and drugs is 0.68.  As the threshold score increases the 
reproducibility increases to 1 (Figure 4). 
 
Conclusion 
Collectively, the early preclinical and current clinical data suggests that this integrated approach 
is highly feasible and safe in neuroblastoma and that it is reproducible among repeat samples 
within patients. It is also clear that an investigation of this approach in other targeted patient 
populations is warranted. Brain tumors, and rare solid tumors are logical diseases in which to 
evaluate this approach, based upon the analogous need to develop a more rational-based approach 
to therapeutic selection in these difficult to treat tumors. Furthermore, the ongoing collaborative 
efforts between the co-investigators of this proposal in identifying novel molecular-based 
treatments for pediatric cancers  and provides further justification to develop this analysis further 
to include DNA mutation analysis in tumor board decision making.  
 
 
Figure 3 Principal Component Analysis. The first 
three principal component scores, PC1-PC3, 
illustrate the observation that the variation 
associated with the six samples for each biopsy 
(all of which have the same symbol and color) is 
small relative to the variation between biopsies.  
 
Figure 4. Reproducibility as a function of the 
threshold score. The reproducibility averaged 
over patients, replicates, and drugs is 0.68 (the 
intercept with the horizontal axis).  As the 
threshold score increases the reproducibility 
increases to 1. 

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2 
STUDY OBJECTIVES 
2.1 
Primary Objectives 
Determine feasibility of using tumor samples to assess genomic mRNA expression arrays and 
DNA mutation panels using predictive modeling to make real-time treatment decisions for 
children with relapsed/refractory cancers. 
 
2.2 
Secondary Objectives 
♦ To continue to determine the safety of allowing a molecular tumor board to determine 
individualized treatment plans  
♦ To determine the activity of treatments chosen based on: 
• 
Overall response rate (ORR)  
• 
Progression free survival (PFS)  
♦ To explore the relationship between tumor phenotype and response by permitting use of 
tumor tissue in a correlative biologic study 
♦ To compare PFS interval to PFS intervals of previous chemotherapy regimens since 
relapse for each subject. 
3 
STUDY DESIGN 
 
This is an open label, multicenter prospective feasibility study in patients with refractory or 
recurrent childhood cancers.   
3.1 
Subject Enrollment and Sample Procurement and Data Processing 
Eligible subjects will be enrolled onto this study at each site following a registration process that 
includes receipt of a signed subject consent form and a copy of the required baseline laboratory 
tests. Subjects will undergo a scheduled surgical resection and/or diagnostic biopsy procedure. 
Common sample identifiers will be provided by the NMTRC Lead Study Coordinator to the 
participating site and will be used by all parties throughout the project to ensure sample, data and 
report alignment between participating organizations.  At the time of tissue resection or biopsy, 
two fresh tumor samples will be committed for this specific research study (referred to as 
“Primary Samples”), and prepared immediately per Appendix II and section 9.3. Primary 
Samples will be sent to Clinical Reference Laboratory (CRL) and Spectrum Health Molecular 
Diagnostics. Samples will be reviewed by local pathology to confirm >75% tumor and >75% 
tumor cell viability which is required for microarray analysis. In the absence of an adequate 
tumor specimen from the enrolled subject, this would represent a non-feasible outcome for this 
subject on the study.  Tumor samples will also be sent for research purposes (referred to as 
“Secondary Samples.”) A portion of the tumor tissue biopsy will be shipped overnight to  the 
Neuroblastoma Translational Research Laboratory on dry ice.  
Upon arrival of the tumor specimens at the Clinical Reference Laboratory (CRL), Spectrum 
Health, the Neuroblastoma Translational Research Laboratory, and TGen, the samples will 
be logged and immediately processed according to details in Section 9. 

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3.2 
RNA Microarray Analysis 
Cells or tumor samples will have RNA isolated and amplified for hybridization to an Affymetrix 
U133 Plus 2.0 GeneChip®. This step will be performed by molecular technologists in 
conjunction with the Clinical Reference Laboratory (CLIA certified lab) in Lenexa, KS. The 
RNA extraction, amplification, hybridization, and scanning procedures adhere to strict standard 
operating procedures to ensure that results are highly accurate and reproducible. The operation 
includes stringent controls over quality including measurements of RNA quality to minimize the 
chance that inaccurate data will be utilized in the study. By default, a failure in an individual step 
will result in a re-run of that specific step if suitable material remains. A second failure will result 
in exclusion of the subject from the study unless an additional fresh surgical specimen can be 
obtained. Standard metrics include the 260/280 ratio and the Agilent 2100 bioanalyzer (Pico 
Chips) which provides a measure RNA degradation as an RNA integrity number (RIN). To pass 
QC, the 260/280 ratio must exceed 1.8 and the RIN number must be greater than 6.5 which 
indicates substantially intact RNA. In the isolation, purification, amplification, and labeling 
processes, a sole individual will handle all samples to limit operator errors. Positive mutation 
findings from the Ion Torrent Panel will be verified using Sanger Sequencing. While all attempts 
will be made to have this data available to the tumor board, due to the potential length of time to 
process Sanger Sequencing samples, these results may not be available until after the tumor board 
has met and the patient has started protocol treatment. If Sanger Sequencing results differ from 
Ion Torrent results and the subject has already started protocol treatment, this information will be 
communicated to the treating site Principal Investigator who will then communicate this 
information to the patient and a mutual decision about continued treatment will be made. 
3.3 
DNA Mutation Panel 
 
Ion Torrent Deep Amplicon Sequencing of Tumor Samples: Deoxyribonucleic acid will be 
extracted from tumor tissues and quantitated using the Qubit2 fluorometer (Invitrogen). Ten 
nanograms of DNA will be used for multiplex PCR of a panel covering 739 mutations in 46 
cancer-related genes (Ion AmpliSeq Cancer Panel, Life Technologies). Subsequent processing of 
samples will be performed according to the manufacturer’s protocol. Library constructions of the 
amplicons and subsequent enrichment of the sequencing beads will be performed using the 
OneTouch system. Sequencing will be done on the 314 chip with 10 megabases capacity using 
the Ion Torrent Personal Genome Machine (Life Technologies) as per the manufacturer’s 
protocol. Data analysis, including alignment to the hg19 human reference genome and base 
calling, is done using built-in software. De-identified Data will be sent to the NMTRC via secure 
e-mail for creation of the DNA Mutation Panel Drug Prediction Report. 
3.4 
Data Analysis and Predictive Methodologies 
Each subject will be assigned a unique anonymous identifier by the Data Manager at the 
Neuroblastoma and Medulloblastoma Translational Research Consortium (NMTRC), which will 
be used to track the “Subject” derived “Samples” and performed “Experiments”.  At each entity 
level, pertinent data can be associated; for example, primary and secondary clinical endpoints can 
ultimately be associated with the Subject and the histopathological assessment of the donated 
Sample, and experimental parameters with each Experiment.  For the proposed work it should be 
adequate to exchange sample information in tables that provide for easy identification of the 
subject identifier.  In addition, the normalized Affymetrix GeneChip data will be associated with 
the Experiment for further analysis as described below.  Upon exchange of the normalized 
GeneChip data and all associated experimental parameters, an additional QC check will be 

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performed to ensure all critical experimental steps passed the required threshold of acceptance.  
While quality control parameters are checked by the CLIA certified laboratory, a secondary 
assessment provides an additional level of quality assurance.  If no failures are noted upon this 
review, a complete analysis of the molecular data will proceed. 
 
3.4.1 Intervention Insights OncInsights mRNA Expression Service 
 
The following describes the Intervention Insights OncInsights service which utilizes data 
generated from the RNA Microarray analysis (as described in section 3.2 above). 
 
A consistent step for the OncInsights methodologies outlined in this proposal is the conversion of 
normalized probe set intensities to a relative measure of transcript abundance.  While many 
studies use an arbitrary fold change threshold relative to a reference sample as a means to 
determine significant changes in gene expression, we prefer to utilize a standardized z-score 
method (described below in Signal Pre-Preprocessing and Z-Score Calculation) to determine 
statistically significant differences in each neuroblastoma sample relative to a whole body 
reference.  This method assigns a z-score to each probe set based upon the number of standard 
deviations from the normal sample population mean.  This provides a good assessment of 
transcript “differences” relative to a whole body reference set which may not necessarily be 
associated with large fold changes in transcript expression. Having established a consistent data 
input of relative transcript abundance in each subjects tumor specimen, the following analytical 
methods will be applied to the standardized data to predict drug efficacy. 
 
Predicted Therapeutic Compounds:  At this time, there are currently greater than 300 drugs 
within the OncInsights system each with a published and defined molecular target.  For the 
purposes of this protocol, the tumor board will only use the drugs listed in Appendix III. 
 
Drug Knowledgebase 
The drug knowledgebase is comprised of publically available, peer-reviewed and clinically 
relevant pharmacological data.  Numerous sources contribute to the knowledgebase including 
GeneGo, DailyMed, DrugBank, UpToDate, Entrez Gene, Entrez Pubmed, PharmaGKB, 
MedTrust Online and MedTrack. 
 
Whole Body Reference Set:  A whole body bank of forty-five normal tissue gene expression 
levels are used as the reference set for the normalization calculations.  A whole body reference 
was chosen to provide a wider variance of tissue specific gene expression for comparison in order 
to best identify expression differences from tumor tissue.  The reference also helps to decrease 
toxicity risk by not identify targets that are highly expressed in normal tissues. 
 
Signal Pre-Processing, Z-Score Calculation and Sibling Probeset Logic 
Signal Pre-Processing.  Signal data from the Affymetrix U133 2.0 Plus GeneChip is normalized 
using Affymetrix’s MAS5.0 Normalization Algorithm.  Using Affymetrix Annotation version 32 
(released August 2011), probesets which map to more than one gene (potential cross-hybridizing) 
are removed from the analysis.  Probesets marked “present” by Affymetrix P/M/A algorithm are 
included in the OncInsights method calculations.  In addition and to include down regulated 
genes, probesets marked “absent” or “marginal” are included in the OncInsights method based on 
the following logic:  probesets with a tumor signal value less than the mean reference signal value 
and the reference probeset is marked “present” by Affymetrix P/M/A logic 50% or more of the 

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time in the whole body reference set.  All probesets which pass the pre-processing thresholds as 
described above are evaluated for inclusion in the OncInsights report. 
 
Z-Score Calculation.  The z-score is calculated for all included probesets using the whole body 
reference mean and whole body reference standard deviation as follows: 
 
 
 
Where x is the signal intensity, µ is the mean probeset intensity from the reference standard and σ 
is the standard deviation of the mean of the reference.  Interpretation of the z-score is 
straightforward and has no special case.  Positive z-scores represent the number of standard 
deviations that the observation being evaluated is above the mean; conversely negative z-scores 
represent the number of standard deviations below the mean.  Observations with high, positive z-
scores are said to be “up-regulated” or “over-expressed” whereas observations with low, negative 
z-scores are said to be “down-regulated” or “under-expressed”.  Finally, it is important to note 
that the z-score represents the individual z-score relative to the same probeset in the normal 
reference group and not its z-score among all other probesets within the total expression data. 
 
Sibling Probeset Logic.  Within the Affymetric Annotation file, numerous probesets map to the 
same Entrez Gene, these probesets are called siblings.  To merge multiple probeset measurements 
(converted to Z-score), the OncInsights systems using an industry accepted logic as follows: 
 
A probeset maps to a single Entrez Gene, the z-score value is assigned to the Entrez Gene. 
 
Two probesets map to a single Entrez Gene, the maximum observed z-score value is assigned 
to the Entrez Gene. 
 
Three or more probesets map to a single gene, the median observed z-score vaule is assigned 
to the Entrex Gene, 
 
Upon conclusion of these methods, the OncInsights system has a list of genes with their 
associated z-score value.  These genes and their measured z-score values are used in all 
subsequent OncInsights methods except the Drug Response Signatures Algorithm which uses 
only probeset values as described below.  
 
BioMarker Based Rules (Sensitive and Insensitive Rules) 
The method employs predefined and published rules maintained in the drug knowledgebase in 
which a drug effect has been associated with an expression of a genomic marker.  This method 
not only predicts drugs which would be suited to treat a specific condition (sensitive), it also flags 
drugs which are predicted to be insensitive given a subject’s tumor biomarker expression 
(insensitive).  Genes with z-score values within the rule range (positive or negative z-score 
values) trigger display of the therapeutic compound.  As an example, one rule within the 
BioMarker Based Algorithm refers to AR, androgen receptor, and bicalutamide.  When tumor AR 
z-score is ≥ +3.0 (three standard deviations above the reference mean) the rule is trigger and 
bicalutamide is included in the OncInsights report.  This is an example of a therapeutic compound 
that is “sensitive” when “over-expressed”.  Other rules trigger “sensitive” when “under-
expressed” as when tumor ERCC1, excision repair cross-complementing repair deficiency, z-
score ≤ -3.0 (three standard deviations below the reference mean) triggers carboplatin as 
x
z
µ
σ
−
=

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“sensitive”.  While simple and practical in nature, one concern with this methodology is that 
over-expression of a drug target can represent a means by which tumors develop resistance to a 
targeted agent [35].  In addition, BioMarker Based Rules can trigger “insensitive” when gene 
expression is “over-expressed” or “under-expressed”.  Currently there are 30 sensitive rules and 
12 insensitive rules within the BioMarker Based Rules knowledgebase.  Each rule is confirmed 
against two or more publically available sources in which the therapeutic agent (drug) has an 
effect on the gene target. 
 
Drug Target Expression Algorithm 
Genes with z-scores ≥ +3 (three standard deviations above the reference mean) are submitted to 
the method and therapeutic compounds which meet the rule requirement are selected and 
displayed in the OncInsights report.  This is analogous to the current approaches of detecting 
Her2 and Egfr gene amplification or over-expression prior to treatment with the appropriate 
targeted inhibitors [59, 60]. For this approach, we utilize public domain knowledge of the existing 
pharmacopeia and their molecular mechanisms of action [38, 39].  For example, one rule within 
the Drug Target Expression Algorithm refers to ESR1, estrogen receptor 1, and tamoxifen.  When 
tumor ESR1 z-score expression is ≥ +3.0  the rule is triggered and tamoxifen is included in the 
OncInsights report.  Currently, 163 rules are contained within the Drug Target Expression 
Algorithm rule set.  Each rule is confirmed against two or more publically available sources in 
which the therapeutic agent (drug) has an inhibitory effect on the gene target. 
 
Network Target Activity (Systems Biology Method, GeneGo) 
A major consideration for the future of predictive therapeutics is the identification of active (or 
inactive) molecular networks within a tumor to permit network-directed therapeutic strategies 
[28, 30, 61].  In partnership with GeneGo  (www.genego.com), we have developed a systems 
wide biology method based upon network topology for predicting drug target status and 
contribution within tumor-specific networks [62].  The method looks at biological pathways by 
constructing a shortest path network within a list of the subject’s genes which are above a 
predefined threshold (z-score ≥ +2).  Using these genes, a global network representing known 
geneomic pathways is constructed using knowledge contained in GeneGo’s master database of 
publically available, peer-reviewed literature describing protein-protein interactions.  These two 
networks are then compared to determine which genes may represent significant pathways with 
respect to the subject’s tumor biology.  Genes are “scored” using the comparison of the two 
networks.  The method is designed to uncover regulatory proteins (kinases, transcription factors) 
which may not be affected at the differential gene expression level, but drive down stream 
transcription activity through transcription factors.  Statistically, this method evaluates the 
enrichment in transcriptional targets compared to the global protein network and evaluates 
whether there is a higher proportion of possible transcriptional targets in the gene set of interest 
than would be expected in a random collection of genes.  This algorithm yields a robust analysis 
of tertiary expression of targets and downstream effects of regulation. 
 
Drug Response Signatures Algorithm (Connectivity Map) 
The method uses a publically available data set called The Connectivity Map developed at the 
Broad Institute [43, 48] and recently commercialized by private equity.  In the original 
description of the method, Lamb et al were able to successfully predict cell lines that were 
responsive to estrogen receptor inhibitors [43].  Subsequently, the general approach has been 
applied to several datasets to hypothesize potential drug efficacy in the background of different 
disease contexts [42, 49].  It was developed to elicit gene expression signatures from human cells 
associated with drug exposure to identify a functional (disease state) connection.  The top 500 

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genes ranked by z-score with a z-score ≥ 1.5 and the bottom 500 genes ranked by z-score with a 
z-score ≤ -1.5 are submitted to the OncInsights Drug Response Signature algorithm.  The 
connectivity score is calculated from a nonparametric, rank-based pattern-matching strategy 
based on the Kolmogorov-Smirnov statistic with p-values estimated by permutation testing 
(n=50,000 tests) as described previously [63, 64].  Upon completion of the analysis, drugs with p-
values ≥ 0.05 (negative enrichment scores) are included in the report.  A negative enrichment 
score implies that genes that are down-regulated by the drug are up-regulated in the tumor sample 
and vice versa.  The implication is that the drug reverses the gene expression changes associated 
with the disease and thus may act to reverse the disease. 
 
Drug Sensitivity Signatures Algorithm (PGSEA) 
The Drug Sensitivity Signatures algorithm reproduces the published implementation of the 
Parametric Gene Set Enrichment Analysis (PGSEA) using the NCI-60 cell line sensitivity 
signatures [44, 45].  A PGSEA drug signature maps over-expressed genes (determined pre-drug 
treatment) to drug sensitivity as measured by the half maximal inhibitory concentration (IC50) of 
the cell line studied.  The drug signature is a collection of Entrez Gene IDs that were found to be 
over-expressed in drug sensitive cells.  Based on this evidence, if a tumor’s gene signature of 
over-expression is similar to a sensitive cell’s gene signature of over-expression the drug may 
also be effective for the tumor cells.  To evaluate potential sensitivity to a signature, a one sample 
t-test is applied to evaluate if the mean of the z-score values is significantly greater than zero.  
The analysis only tests for a difference in the positive z-score direction.  A negative z-score trend 
even if it is significant is discarded.  This approach is consistent with well published methods for 
inferring drug sensitivity utilizing the NCI 60 cell line dataset [45, 51]. 
 
OncInsights Version. 
The study will use OncInsights version 1.4.7.0 
 
3.4.2 DNA Mutation Panel Analysis 
 
The following describes a process which utilizes data generated from the DNA Mutation 
Panel analysis (as described in section 3.3 above).   
 
DNA Mutation Panel Drug Prediction 
The data from the Spectrum Health Ion Torrent Cancer Panel will be provided to the NMTRC.. A 
knowledge database created from published research literature linking mutations with targeted 
drugs in cancers will provide a report for the tumor board showing the mutations and predicted 
therapeutics from the list provided in Appendix III.  
 
An in-house software application is implemented that produces reproducible, rules-based lists 
linking gene mutations with potential drug therapies. An electronic rule-capture interface is used 
to import a spreadsheet database, that contains genes, measurement types, and values for those 
measurements, and any other additional columns. Rules (for each gene) are assigned to the 
application by the investigators, without modifying the core software code. All conditions follow 
the basic form "<measurement> <verb> <value>". These verbs include <, <=, >, >=, equals, is 
present, is not present. Every rule may have any number of modifiers that effectively serve as 
sub-rules that associate the rule with other potential drug treatment for the parent rule.  
 
 

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Report: 
The process of report generation begins with gene specific input with accompanying aberration 
data. If gene matches gene in the database then aberration is checked. This will generate a rule in 
table-format stating a direct relationship, indicate/do not indicate drug. If an aberration is not 
exactly matched it will trigger an inferred relationship, indicate/do not indicate drug. The 
generated report includes a PubMed ID for each rule, which will be included as both 
supplementary data and an outbound hyperlink. The software enables only authorized 
investigators to access the underlying system configuration. Users of this application are able to 
access the data only through the GUI "front-end", thereby locking the data relationships for the 
duration of an investigational trial. This software takes into account the following: 
1. 100% reproducible output given the same input.  
2. Simple yet sophisticated rules management.  
3. Cross reference data with several open source data sets. 
4. Generation of a clinically understandable, actionable report. 
 
Positive mutation findings from the Ion Torrent Panel will be verified using Sanger Sequencing. 
While all attempts will be made to have this data available to the tumor board, due to the potential 
length of time to process Sanger Sequencing samples, these results may not be available until 
after the tumor board has met and the patient has started protocol treatment. If Sanger Sequencing 
results differ from Ion Torrent results and the subject has already started protocol treatment, this 
information will be communicated to the treating site Principal Investigator who will then 
communicate this information to the patient and a mutual decision about continued treatment will 
be made. 
3.5 
Treatment Protocol Decision 
3.5.1 Decision Making Rules for Treatment Regimens 
Treatments protocols will be generated from the tumor board meeting which will consists of three 
pediatric oncologists (minimum) and one pharmacist utilizing the information contained in a 
report generated on the basis of genomic analysis of the gene expression profile of the subject’s 
tumor. Specific treatment details will consist of a regimen chosen from a guided list of agents 
implicated in critical molecular signaling pathways and/or from signature-based predictions of 
drug efficacy summarized in the guided therapy reports. All agents are listed in the current 
pharmacopoeia for human use, but will differ amongst individual subjects. 
3.5.1.1 Decision rules for the committee will include:  
1. All drugs with predicted efficacy will be reported to the tumor board with an associated 
predicted efficacy score and rank. At this time, FDA approved drugs predicted by one of 
the different predictive methodologies under evaluation will be included (Drug Target 
Expression, Biomarker-Based Rules Algorithm, Systems Biology Methods, Connectivity 
Map, Gene Set Enrichment Analysis, or DNA mutation panel). For these panels the 
analytical methods are independently applied to the standardized and normalized (relative 
to whole body reference set) gene expression data derived from the profiling of each 
subject’s tumor. Each method is associated with an objective statistical threshold that 
must be exceeded in order for a specific drug to be predicted and reported for 
consideration. Multiple lines of evidence (e.g. multiple methods predicting the same 
drug, multiple targets for the same drug) will be considered during the review process. 

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Molecular-based predictions of drug efficacy will be supplemented with evidence 
gathered from automated searching of the literature, clinical trials and the internet.  
2. Drugs must be FDA approved with established standard and safe dosing schedules (see 
drug dosing below Section 3.5.1.2). Those without known pediatric dosing will be 
excluded. 
3. Potential drug choices will be analyzed with regards to safety, mechanism, availability 
and cost. Focus will be on low-toxicity, targeted therapies.  
4. Drug combinations will be allowed, up to a maximum of 4 agents. Literature searches 
will be conducted to assemble data on previously established and tested regimens. These 
regimens will be given priority. 
5.  A pharmacist will analyze potential drug interactions between the guided agents and the 
subject’s routine medications and supplements. For drug interactions and known 
toxicities the following databases will be used: MicroMedex LexiComp, E-facts, Natural 
Medicines Database.  
Subjects’ history and previously received treatments will be reviewed. Drugs which a subject 
has failed will be given low priority and used only if there is a rationale for synergy in 
combination therapy. 
3.5.1.2 Recommended priorities for determining drug dosing to be used in 
individualized treatment plans include the following: 
1. For a given proposed individualized combination of drugs the first priority to establish 
doses will be to identify the same combination of drugs in a peer-reviewed journal article 
or presented as a reviewed abstract, or which is part of an ongoing peer-reviewed clinical 
trial registered with clinical trials.gov. 
2. When a proposed individualized combination of drugs has not previously been reported, 
the process to establish doses will be to then identify individual members of the proposed 
combination that have been used in combination with other cytotoxic agents similar to 
those being considered for combination therapy. The source of information will be a 
peer-reviewed journal article or presented as a reviewed abstract, or which is part of an 
ongoing peer-reviewed clinical trial registered with clinical trials.gov. 
3. When a proposed individualized combination of drugs have no available combination 
data, dosing guidelines will start with the MTD determined from a phase I/II pediatric 
study.  Reference information will be based upon either a peer-reviewed journal article or 
presented as a reviewed abstract, or which is part of an ongoing peer-reviewed clinical 
trial registered with clinical trials.gov.  Doses will be reduced to compensate for potential 
additive toxicities of combination agents (refer to protocol section 3.5.1.1 #5 that 
describes pharmacy  programs that are used to evaluate potential interactions and 
combination dosing for all medications).  
Please note that many of the drugs that will be considered for proposed individualized 
combination therapy in this protocol are not considered cytotoxic agents and therefore will not 
have previously been specifically tested as part of conventional antineoplastic protocols. 
Examples of these medications may include anti-seizure or anti-cholesterol agents. These non-
cytotoxic agents will be used at standard doses based on recommendations of an experienced 
pediatric pharmacist (refer to protocol section 3.5.1.1 #5 that describes pharmacy programs that 
are used to evaluate potential interactions and combination dosing for all medications). The final 
treatment regimen will be subjected to a 12 hour in depth review and evaluation for safety and 

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then be signed off by one of the protocol pharmacists. The treatment memo will then be discussed 
with the subject and their parents (if the subject is < 18 years of age). 
3.6 
Safety Evaluations 
The principal investigator and the study chairs will evaluate reported serious adverse events and 
other toxicities in real time.  Study chair and PI meetings will occur at least monthly. The 
principal investigator will meet with the clinical research team at frequent and regularly 
scheduled intervals to determine treatment modifications and treatment based toxicities. Toxicity 
data must be submitted to the disease specific Study Chair at the end of each cycle of therapy. 
 
Any safety concern or new information that might affect either the safety or the ethical conduct of 
this trial will be immediately forwarded to the study chairs in written form.  The study chairs will 
be responsible for informing the IRB and DSMB.  If trends in toxicities are noted or stopping 
rules are met, the PI will temporarily suspend enrollment while reviewing the episodes with the 
IRB and DSMB. The DSMB will convene every 6 months for evaluation of all safety data. 
Study will be on hold for safety monitoring by DSMB review when: 
1. Any deaths deemed related to the study drug by the treating PI while on study or 
occurring less than 30 days after medications ended or 2 serious adverse events 
possibly related to protocol within 60 days. 
2. Any other reason that the NMTRC feels it is in the best safety interest of the subjects.  
 
Subjects will be required to either come off study or be dose reduced per treating physician 
standard of care if one of the following toxicities related to treatment regimen occurs. Toxicity 
will be graded according to the NCI-Common Terminology Criteria for Adverse Events (CTCAE 
v4.0). 
 
 
Non-Hematologic toxicity: 
 
∙ ≥Grade 3 non-hematological toxicity not resolved to <Grade 2 or baseline 
within 2 weeks excluding nausea, vomiting, anorexia, hypertension, electrolyte 
abnormalities corrected with oral supplementation 
 
∙ Any Grade 4 non-hematological toxicity. 
 
 
Hematologic toxicity: 
 
∙ Grade 4 neutropenia lasting ≥14 days; 
 
∙ Grade 4 neutropenia with Grade 4 infection 
 
 
  

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3.7 
Efficacy Evaluations  
At the times indicated in Section 5 and the Table of Procedures and Assessments, scans will be 
obtained to evaluate response data for subjects enrolled in this study. Efficacy will be assessed 
according to criteria outlined in Section 7 (Efficacy Assessments) to evaluate the activity and 
potential benefit of the chosen treatments protocol in this subject population.  
 
3.8 
Biological Studies  
Subjects will have an opportunity to participate in correlative biological studies on a voluntary 
basis. This study will be used to correlate in vivo and in vitro predictive drug responses.  This 
study may be able to contribute to our knowledge of molecular determinants of response to 
therapy and/or development of biomarkers to help guide future therapy. 
 
4 
 SUBJECT SELECTION 
4.1 
Inclusion Criteria 
1. Subjects must have histologically proven neuroblastoma, brain tumor, or rare tumor and 
confirmation of refractory or recurrent disease with histologic confirmation at diagnosis or at 
the time of recurrence/progression  
2. Subjects must be age >12 months at enrollment. 
3. Subjects must be age  ≤ 21 years at initial diagnosis. 
4. Subjects must have measurable disease as demonstrated by residual abnormal tissue at a 
primary or metastatic site measuring more than 1 cm in any dimension by standardized 
imaging (CT or MRI); tumor must be accessible for biopsy. Patients with bone marrow only 
disease expected to be >75% tumor are eligible to enroll. 
5. Current disease state must be one for which there is currently no known curative therapy   
6. Lansky or Karnofsky Score must be more than 50 
7. Subjects without bone marrow metastases must have an ANC > 750/μl  
8. Adequate liver function must be demonstrated, defined as: 
a. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND 
b. ALT (SGPT) < 10 x upper limit of normal (ULN) for age 
9. A negative serum pregnancy test is required for female participants of child bearing potential 
(≥13 years of age or after onset of menses) 
10. Both male and female post-pubertal study subjects need to agree to use one of the more 
effective birth control methods during treatment and for six months after treatment is 
stopped. These methods include total abstinence (no sex), oral contraceptives (“the pill”), an 
intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone 
acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam 
with a condom is recommended. 
11. Informed Consent: All subjects and/or legal guardians must sign informed written consent. 
Assent, when appropriate, will be obtained according to institutional guidelines. Voluntary 
consent for optional biology studies will be included. 

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4.2 
Exclusion Criteria 
1. Subjects who have received any cytotoxic chemotherapy within the last 7 days prior to 
enrollment and 14 days prior to study treatment start date.   
2. Subjects who have received any radiotherapy to the primary sample site within the last 14 
days (radiation may be included in treatment decision after biopsy). 
3. Subjects receiving anti-tumor therapy for their disease or any investigational drug 
concurrently 
4. Subjects with serious infection or a life-threatening illness (unrelated to tumor) that is > 
Grade 2 (NCI CTCAE V4.0), or active, serious infections requiring parenteral antibiotic 
therapy. 
5. Subjects with any other medical condition, including malabsorption syndromes, mental 
illness or substance abuse, deemed by the Investigator to be likely to interfere with the 
interpretation of the results or which would interfere with a subject’s ability to sign or the 
legal guardian’s ability to sign the informed consent, and subject’s ability to cooperate and 
participate in the study  
 
5 
STUDY PROCEDURES AND ASSESSMENTS  
5.1 
Enrollment of Subjects  
 
All subjects (or subjects’ legal representatives) must provide written informed consent before any 
study specific assessments may be performed. The NMTRC will keep a “possible enrollment list” 
for all sites combined. Subjects will be allowed to enroll in the order that they are added to that 
list. Prior to consent of the subject, the NMTRC research coordinator will be contacted (via e-
mail) to place subject on this possible enrollment list. The NMTRC coordinator will then reply 
with study space availability. If a spot is not available at that time, the site will be contacted as 
soon as a spot does open up (based on the subjects order on the list). If a spot is available at the 
time, the potential subject will undergo consent and completion of all required screening 
procedures and certification of all inclusion and exclusion criteria by the Investigator. If the 
subject fits all enrollment criteria, the site will again contact the coordinator at the NMTRC for 
official enrollment confirmation and unique subject identifier assignment. In addition, a study 
enrollment form will be e-mailed or faxed to the coordinator at the NMTRC. A subject may NOT 
be enrolled on trial until official approval from the NMTRC is received. When a spot becomes 
available, the first subject from the list will be contacted and will have 5 working days with which 
to enroll in the study. If this subject does not enroll by that time then the subject forfeits his/her 
spot and the next subject will be offered that spot.  
 
 
 
 
 
 
 
 

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5.2 
Screening  
The Investigator is responsible for keeping a record of all subjects screened for entry into the 
study and subsequently excluded.  
 
The following screening procedures must be performed within 21 days (14 days preferred) 
prior to date of biopsy.  Studies must be done after last previous treatment for malignancy: 
 
1. Signed informed consent form. All subjects (or subjects’ legal representatives) must 
provide written informed consent before any study specific assessments may be 
performed. Signed informed consent form for voluntary participation in correlative 
biologic analysis.  
2. Complete medical and surgical history, including documentation of the histologic 
evidence of malignancy and prior treatments for cancer. Include all other pertinent 
medical conditions and a careful history of all prior medical treatments;  
3. Demographics;  
4. Physical examination (including height and weight), noting all abnormalities and sites of 
palpable neoplastic disease;  
5. Vital signs, including temperature, pulse rate, and blood pressure;  
6. Karnofsky Performance status/Lansky Play status (Appendix I); 
7. CBC with differential; 
8. Serum electrolytes (sodium, potassium, chloride, bicarbonate), blood urea nitrogen 
(BUN), creatinine, albumin, Bilirubin, LDH, ALT, and AST; 
9. Serum pregnancy test for female subjects of child bearing potential (onset of menses or 
≥13 years of age); 
10. CT or MRI of measurable disease sites  
11. Solid tumor biopsy for “Primary Sample” with remaining tumor tissue used in correlative 
biologic studies handled per section 9.3 and submitted per Appendix II.  
For subjects that cannot provide a solid tumor biopsy; a bone marrow core biopsy sample 
will replace the solid tumor sample as the “Primary Sample.” Bone Marrow must have 
adequate tumor (defined as >75% tumor) in order to qualify as “Primary Sample.”  
12. Concomitant medications/therapies including documentation of steroid use and dose; 
13. Confirmation of inclusion and exclusion requirements; 
 
Following completion of all required screening procedures and certification of all inclusion and 
exclusion criteria by the Investigator, the coordinator at the NMTRC will be contacted (via e-mail 
or phone call), at which time the subject will be enrolled in the trial and a unique subject number 
assigned.  
 
 
 
 
 
 
 
 

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The following screening procedures must be performed within 21 days of enrollment (14 
days preferred). These procedures must be done prior to the first dose of study drug, but 
are not required to be done before biopsy.  
1. Neuroblastoma subjects: MIBG scan (not required if subject’s disease is previously 
determined to be non-avid). PET may be considered as alternative for MIBG. Other 
imaging appropriate for tumor type may also be considered. 
2. Any subject that is suspected to have possible bone marrow disease and for all 
neuroblastoma subjects: Bone marrow aspirate and biopsy. Additional bone marrow for 
correlative biologic studies will be handled per section 9.3 and submitted as per 
Appendix II.  
3. Baseline EKG (as indicated) 
4. Neuroblastoma subjects: Urine for Vanillylmandelic Acid (VMA) & Homovanillic Acid 
(HVA) 
5. Specific Tumor Marker for defined disease (if available) 
6. Completion (by study staff) of pre study case report forms  
7. Any additional labs or testing required by the tumor board 
5.3 
Study Procedures/Study Interventions 
5.3.1 Study Visits- Cycle 1 Day 1  
 
Subjects will return to the enrolling clinic at Day 1 of cycle 1 for evaluations.  The following 
evaluations will be conducted prior to starting study drug: 
1. Physical examination (including body weight); 
2. Karnofsky Performance status/Lansky Play status-Appendix I; 
3. Vital signs, including weight, temperature, pulse rate, and blood pressure (sitting); 
4. CBC with differential; 
5. Serum electrolytes, BUN, creatinine, Bilirubin, ALT, AST, LDH; 
6. Neuroblastoma subjects: Urine for Vanillylmandelic Acid (VMA) & Homovanillic Acid 
(HVA) (may have been done within 3 days of treatment start/day 1) 
7. Specific Tumor Marker for defined disease (if available) (may have been done within 3 
days of treatment start/day 1) 
8. Review and recording of concomitant medications; 
9. Monitoring of AEs and review of concurrent illnesses 
10. Completion (by study staff) of Case Report Forms. 
11. Any additional labs or testing required by the tumor board 
5.3.2 Study Visits- Cycle 1 Day 8 (± 3 days) 
Subjects will return to the enrolling clinic at Day 8 of cycle 1 for evaluations.  The following 
evaluations will be conducted at those time points: 
1. Physical examination;  
2. CBC with differential; 
3. Monitoring of AEs and review of concurrent illnesses  
4. Review and recording of concomitant medications; 
5. Completion (by study staff) of Case Report Forms. 
6. Any additional labs or testing required by the tumor board 

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5.3.3 Study Visits- Cycle 1 Day 15 (± 3 days) 
 
Subjects will return to the enrolling clinic at Day 15 of cycle 1 for evaluations.  The following 
evaluations will be conducted at those time points: 
1. Physical exam; 
2. Karnofsky Performance status/Lansky Play status-Appendix I; 
3. Vital signs, including temperature, pulse rate, and blood pressure (sitting); 
4. CBC with differential; 
5. Serum electrolytes, BUN, creatinine, Bilirubin, ALT, AST, LDH; 
6. Review and recording of concomitant medications; 
7. Monitoring of AEs and review of concurrent illnesses 
8. Completion (by study staff) of Case Report Forms. 
9. Any additional labs or testing required by the tumor board 
 
 
 
5.3.4 Study Visits- Cycle 1 Day 22 (± 3 days)-  for 28 day cycles only 
 
Subjects will return to the enrolling clinic at Day 22 of cycle 1 for evaluations.  The following 
evaluations will be conducted at those time points: 
1. Physical examination;  
2. CBC with differential; 
3. Monitoring of AEs and review of concurrent illnesses  
4. Review and recording of concomitant medications; 
5. Completion (by study staff) of Case Report Forms. 
6. Any additional labs or testing required by the tumor board 
 
5.3.5 Completion of Protocol Defined Therapy 
 
Subjects who receive one total cycle of treatment (21 or 28 days) will be considered as 
having completed the protocol defined therapy for feasibility. Additional treatment cycles 
may be delivered in a maintenance setting if there are no safety concerns, there is no disease 
progression, and/or there is an indication of clinical benefit.  Maintenance monitoring will be 
conducted as described for Subsequent Cycles. 
 
 
 
 
 
 

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5.3.6 Subsequent Cycles (Maintenance Protocol Treatment Cycles)  (+/- 3 days to start 
Day 1 of Cycle treatment) 
 
Drug administration will be according to guidelines in previous cycles with dose modifications if 
needed per Section 6.1.1. The following evaluations will be performed on day 1  of each cycle as 
indicated.  Evaluations will be performed within 5 days prior to dosing unless otherwise 
indicated.  Subsequent cycles (cycles 2 and beyond) may be given at the subject’s home 
institution. If subjects are to receive subsequent cycles at a home institution, this will occur only 
at COG (Children’s Oncology Group) member hospitals or those specifically approved by FDA. 
 
1. Physical examination; 
2. Karnofsky Performance status/Lansky Play status-Appendix I; 
3. Vital signs, including weight, BSA, temperature, pulse rate, and blood pressure (sitting); 
(must be done on Day 1) 
4. CBC with differential; 
5. Serum electrolytes, BUN, creatinine, Bilirubin, ALT, AST, LDH; 
6. Neuroblastoma subjects: Urine for Vanillylmandelic Acid (VMA) & Homovanillic Acid 
(HVA) 
7. Specific Tumor Marker for defined disease (if available) 
8. Review and recording of concomitant medications; 
9. Monitoring of AEs and review of concurrent illnesses (must be done on Day 1) 
10. Completion (by study staff) of Case Report Forms. 
11. Any additional labs or testing required by the tumor board 
 
5.3.7 Reevaluation During Subsequent (Maintenance) Cycles 
Subjects will be assessed for disease at the end of cycle 2 and every other cycle or every 8 
weeks, whichever occurs first, with the following (timing should be during the last week of 
the cycle):  
1. CT or MRI of measurable disease sites (same as study done at study entry); 
2. Neuroblastoma subjects only: MIBG scan or PET scan same as/if done at baseline 
evaluation. 
3. Neuroblastoma subjects and any other subject with suspected bone marrow disease  
with positive bone marrow diease at study entry: Bone marrow aspirate and biopsy; 
Monitoring of AEs and review of concurrent illnesses  
4. Review and recording of concomitant medications; 
5. Any additional labs or testing required by the tumor board 
6. Additional imagining or studies may be done at any time if clinically indicated by 
symptoms, exam, or tumor markers. 
 
 
 
 

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5.3.8 Off Therapy/30 Day Follow-Up Visit 
 
Subjects will be seen at either the study clinic or their home institution within 30 (+7) days after 
the last dose of treatment. Last dose of treatment is defined as the last day that the subject 
receives the combination of tumor board recommended treatments.  The following evaluations 
will be conducted: 
1. Physical examination (including body weight), focusing on an update of all previous 
abnormalities, any new abnormalities; 
2. Vital signs, including temperature, pulse rate, blood pressure (sitting); 
3.  Karnofsky Performance status/Lansky Play status (Appendix I); 
4. CBC with differential; 
5. Serum electrolytes, BUN, creatinine, Bilirubin, LDH, ALT, AST; 
6. Neuroblastoma subjects: Urine for Vanillylmandelic Acid (VMA) & Homovanillic Acid 
(HVA) 
7. Specific tumor Marker for defined disease (if available) 
8. Review and recording of concomitant medications; 
9. Monitoring of AEs and review of concurrent illnesses 
10. Completion (by study staff) of Case Report Forms  
 
Any subject with a suspected study drug-related toxicity at the follow-up visit must be 
followed until all current drug-related adverse events have resolved to baseline or ≤ Grade 2 
or stabilization of the event.  This may require additional clinical assessments and laboratory 
tests.  The follow-up results will be recorded on the appropriate page of the CRF, as well as 
in the subject's source documentation. 
 
6 
Protocol Drugs 
Specific treatment details will consist of a regimen chosen from a guided list of agents implicated 
in critical molecular signaling pathways and/or from signature-based predictions of drug efficacy 
summarized from the guided therapy report. All agents are listed in the current pharmacopoeia for 
human use, but will differ amongst individual subjects. The treatment regimen will consist of 
FDA approved drugs that have known dosing per Section 3.5.1.2. The treatment regimens will be 
discussed with families and will include review of known side effects per  Pharmacopeia Library 
(Appendix III) (information obtained from package insert and from MicroMedex LexiComp, E-
facts, and Natural Medicines Database), serious adverse effects of possible new drug 
combinations, and any additional clinical monitoring that may be recommended by the tumor 
board. The family will be given the option to proceed with therapy and if the family decides to 
proceed with the tumor board’s treatment decision they will be asked to sign a treatment specific 
memo.  
 
Drugs will be prescribed by the enrolling institution per treating hospital protocol and 
administered per FDA guidelines and tumor board recommendations.  
 
 
 
 

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6.1.1 Treatment modifications 
Dosing delays and modifications will be at the discretion of the treating Principal Investigator and 
their institutional pharmacist and based upon the selected therapy, subject response and practiced 
dosing regimens. Decisions will be made on the basis of clinical expertise of the physicians and 
pharmacists and with the subject’s welfare being the principal concern. Informational websites 
such as drug bank (Micromedex, Lexicomp, E-facts, Natural Medicines Database) will be utilized 
to identify potential adverse events associated with individual treatments. The study pharmacist 
will be available to consult on decisions made with respect to changes and modification made due 
to potential drug related adverse events. 
6.2 
Concomitant Medications and Treatments  
All intercurrent medical conditions will be treated at the discretion of the Investigator according 
to acceptable community standards of medical care. All concomitant medications and treatments 
will be documented on the appropriate case report form.  
 
The following medications are not permitted during the trial:  
• 
Any cytotoxic chemotherapy  
• 
Any other investigational treatment  
• 
Any other systemic anti-neoplastic therapy including, but not limited to, immunotherapy, 
hormonal therapy, targeted therapies, anti-angiogenic therapies, or monoclonal antibody 
therapy  
 
The following medications/treatments may be administered as follows:  
• 
Any radiotherapy administered with palliative intent/pain control or recommended by 
tumor board as part of therapeutic regimen for best patient care. 
• 
Prophylactic filgrastim, pegfilgrastim or oprelvekin; these hematopoietic growth factors 
may be administered according to ASCO, ASH, or institutional guidelines to treat an 
established cytopenia  
• 
Erythropoietin, blood products, anti-emetics, steroids, and transfusions may be 
administered at the discretion of the Investigator based on established criteria. 
 
 

 
 
 
 
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7 
Efficacy Assessments  
7.1 
Tumor Assessments/Scans  
Tumor assessments/imaging studies must be obtained at baseline, at the end of cycle 2 and again 
after every other cycle (or every 8 weeks, whichever occurs first). The same method of 
assessment and the same technique should be used to characterize each identified and reported 
lesion at baseline and during follow-up.  
 
All radiological images must be available for source verification. Images may be submitted for 
extramural review for final assessment of antitumor activity.  
Subjects who come off study should have a final end of study disease-specific assessment done 
when possible. 
 
7.2 
Scan Submission:  
All required study scans (CT’s, MRI’s, MIBG’s and PET’s) will be de-identified and sent to the 
NMTRC. All study required de-identified scans will be uploaded to HIPAA compliant database 
(if available) or sent on disc to: 
 
Alyssa VanderWerff 
NMTRC 
Clinical Program Coordinator 
100 Michigan Avenue NE  MC 272         
Grand Rapids, MI 49503 
Tel:  (616) 267-0327  
E-Mail:  Alyssa.VanderWerff@ helendevoschildrens.org  
7.3 
Response Criteria 
Overall response rate (ORR) in subjects with radiologically assessable disease will be determined 
by CT or MRI by cross-sectional imaging, MIBG/PET scans, and/or bone marrow assessment.  
Response Assessment: Each subject will be classified according to their “best response” for the 
purposes of analysis of treatment effect. Best response is determined from the sequence of the 
objective statuses described below. 
Response Criteria for Subjects with Solid Tumors: This study will use the (RECIST) 
Response Evaluation Criteria measurements in Solid Tumor from the NCI (Therasse, et al, 2000) 
modified for pediatrics. 
• Measurable disease: The presence of at least one lesion that can be accurately measured in at 
least one dimension with the longest diameter at least 10 mm 
• Serial measurements of lesions are to be done with CT or MRI, using the same method of 
assessment is to be used to characterize each identified and reported lesion at baseline and 
during follow-up. 
• Quantification of Disease Burden The sum of the longest diameter (LD) for all target lesions 
will be calculated and reported as the disease measurement.  For this evaluation, all scans will 
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• Complete Response (CR): Disappearance of all target lesions. 
• Partial Response (PR): At least a 30% decrease in the disease measurement, taking as 
reference the disease measurement done to confirm measurable disease at study entry. 
• Stable Disease (SD): Neither sufficient decrease to qualify for PR or sufficient increase to 
qualify for PD from study entry. 
• Progressive Disease (PD):  At least a 20% increase in the sum of the longest diameters of all 
target lesions compared to study entry, the appearance of unequivocal new lesions, or 
laboratory evidence of clinical progression (e.g., spread to bone marrow or increasing 
catecholamines). 
 
Response Criteria for Subjects with Bone Marrow Disease:  
• Those subjects with morphologic evidence of neuroblastoma by routine H and E staining 
(NSE staining only is not evaluable) will be evaluable to assess bone marrow response. 
• Complete response: No tumor cells detectable by routine morphology on two subsequent 
bilateral bone marrow aspirates and biopsies done at least three weeks apart after study entry. 
• Progressive disease: Tumor seen on morphology on two consecutive bone marrows done at 
least three weeks apart in subjects who had NO tumor in bone marrow at study entry. (Note: 
Subject may be declared as progressive disease in bone marrow after only one diagnostic bone 
marrow at the discretion of the treating physician after discussion with the study chair.) 
• Stable disease: Persistence of an amount of tumor in the bone marrow by morphology that 
does not meet criteria for either complete response or progressive disease. 
 
 
Response Criteria for Subjects with MIBG or PET Positive Lesions 
• Subjects who have a positive MIBG or PET scan at the start of therapy will be evaluable for 
MIBG or PET response. All MIBG’s and PET scans will be performed at the research 
institution and then centrally reviewed. 
• Complete response = complete resolution of all positive lesions 
• Partial response = resolution of at least one positive lesion, with persistence of other MIBG 
positive lesions. 
• Stable disease = no change in scan in number of positive lesions (includes subjects who have 
same number of positive lesions but decreased intensity) 
• Progressive disease = Development of new positive lesions 
 
Duration of response: 
Duration of response is defined as the period of time from when measurement criteria are met for 
complete response (CR) or partial response (PR), whichever is first recorded, until the first date 
that recurrent or progressive disease (PD) is objectively documented (taking as reference for PD 
the smallest measurements recorded since the treatment started). 
The assessment of response will include the initial measurable targets and will be performed after 
the first and second cycle, then after every other cycle (or 8 weeks, whichever occurs first). Serial 
results of bone marrow aspirates, biopsies and urinary catecholamines will be reviewed for 
responding subjects to confirm response or lack of progression.   
 
Clinical Response 
A subject will be defined as having a clinical response if they have stable disease or better and a 
decrease in their tumor markers by ≥ 50%. Clinical response will also be defined as a subject that 
has a complete clearing of a previously positive bone marrow while on study.  

 
 
 
 
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Progression Free Survival 
Time to progression, defined as the period from the first day of administration of study drug until 
the criteria for progression are met taking as reference the screening measurements, will be 
assessed.   
8 
Sample Size Justification  
 
Feasibility 
Since this is primarily a feasibility trial, the definition of feasibility for this study will include: 
 
“Enrollment onto study, RNA expression profile completed, DNA Mutation Panel 
completed, genomic analysis and report generation, tumor board held with treatment 
decision, treatment review completed and start of treatment by 21 days post biopsy/surgical 
resection date, and then completion of 1 cycle of therapy.” 
 
Our preliminary results for 5 subjects indicates that we have a sample collection success rate of 
5/5 (100%) subjects, a genetic report profile success rate of 5/5 (100%) within the 7-10 day time 
window as well as a treatment agreement success rate of 5/5 (100%) within the 5 day time 
window.  The average time (+/-SD) for completion of the genetic profile was 6.6 days (+/-1.7 
days) with a median of 7 days.  The average time (+/-SD) for time to Treatment was 3.2 days (+/-
0.8 days) with a median of 3 days.  Data preliminary to date for each of these three feasibility 
markers are very consistent with our anticipated performance standards.  
  
Our initial feasibility trial continues to show that it is feasible and safe to use RNA expression 
analysis for tumor boards creating treatment decisions for patients without curative options. This 
study will ask the feasibility of adding a DNA mutation panel and expansion to other non-
curative pediatric cancers as well. 
 
 
Assumptions:  The feasibility outcome is a binary measure for each of the three clinical strata 
with a lower success null value of 50% which would require reconsideration of the full process 
and an upper success value of 75% for the alternative which would be deemed worthy of further 
consideration for an efficacy trial at the next phase. A binomial distribution was used for the 
testing process with a combination of Type I error levels (10%) and Power (75%).  The basic 
design overall is a MiniMax approach which minimizes the overall sample size. The MiniMax 
design with an interim look will require an overall sample size of n = 16.  Each of the three 
clinical strata will use a two stage decision rule. 
 
The Two-Stage Stopping Rule for each of the three strata is as follows: 
 
Stage 1: Stop and accept the null hypothesis if the observed feasibility rate is less than or equal to 
5/9.  Otherwise, continue to stage 2. 
 
The probability of stopping for futility is 0.746 when Ho is true and 0.166 when Ha is true. 
 
Stage 2: Stop and accept the null hypothesis if the observed feasibility rate is less than or equal to 
10/16.  Otherwise, stop and reject the null hypothesis. 
 
 

 
 
 
 
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9 
Laboratory Evaluations 
9.1 
Specimens to be Collected, Schedule and Amount 
Required samples will be collected at the start of study. Recommended/Secondary 
(volunteer/optional) samples will also be collected at the start of study. Additionally, 
optional bone marrow samples will be collected every 6-8 weeks per Study Procedure 
Table. 
 
9.2 
Tumor collection and correlative biology studies. 
 
Viable, fresh tumor >0.2grams from tumor biopsy should be placed in neurobasal tissue culture 
media using sterile technique for, cell line and xenograft generation.  Viable, fresh tumor 
>0.2grams will also be placed in kit for RNA for CRL laboratory and >0.2grams will be fresh 
frozen to be shipped to  the Neuroblastoma Translational Research Laboratory for RNA 
analysis and to TGen for RNA and DNA sequencing analysis along with 4-6ml blood sample in a 
PAXgene tube. Samples should be labeled with subjects study number. If excess tissue is 
available, then snap frozen tumor tissue approximately 5mm in size should be wrapped in foil, 
snap frozen in liquid nitrogen and stored at -80ºC. Tissue samples will be coded. Fixed tissue 
remaining from diagnostic evaluation may be used.  Bone marrow samples will also be sent to the 
Neuroblastoma Translational Research Laboratory for tumor cell isolation and culture and 
Spectrum Health to be sorted by flow cytometry using the immunophenotyping six-color, 
ganglioside GD2, analysis using monoclonal antibodies to membrane antigen expression of 
ganglioside GD2FITC dye, CD81FITCdye, the absence of CD45PerCPdyeleukocytic antigen, and the 
presence of CD56APC NCAM antigen, CD9, and/or CD34.  Cells or tumor samples will have RNA 
isolated and run on an Affymetrix U133+ Array chip. Data will be analyzed for comparison of 
bone marrow tumor and solid tumor expression profiles. 
 
At the Neuroblastoma Translational Research Laboratory tumor cells will be grown to 70% 
confluency in neurobasal media with EGF and FGF. Cell lines will be maintained in culture for 
biology studies. These will include determining the growth curves and responsiveness of cells 
derived from these tumors to a variety of agents identified on the report in vitro (both the chosen 
regimen as well as alternate options). Cells will be injected into the inguinal fat pad of NOD 
SCID mice for generation of subject xenografts. These mice will be used for correlative drug 
testing experiments based on predictive models. Evaluation of mechanism of action of new drug 
combinations will be evaluated in mice models through immunohistochemical staining and 
western blotting of tumor preps. These models will allow us the opportunity to evaluate alternate 
drug combinations that might have been superior to the chosen regimen. 
 
 

 
 
 
 
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9.3 
Detailed Procedure For Sending Subject Samples: 
 
At screening, subjects will have biopsy samples sent. The main sample for study report will be 
referred to as the “Primary Sample.”  
 
The “Primary Sample” will be a current solid tumor biopsy or core bone marrow biopsy (with 
>75% tumor). 
 
If a solid tumor sample cannot be obtained and the subject’s bone marrow is <75%  tumor then 
they will be ineligible for study. 
 
In addition to the “Primary Sample”, if subjects have signed the additional consent for optional 
sample collection, they will also have these secondary samples sent as follows.  
 
9.3.1 Sample Procurement and Shipping at Screening:   
 
De-identified subject tumor samples will be sent on all subjects as following: 
 
Label all tubes with subject’s unique identifier, date/time of sample collection, and 
contents (i.e. solid tumor, bone marrow, blood). 
 
9.3.1.1 Send the following Required Primary Samples for All Tumor Types (along with 
appropriate forms) 
 
1. Sample 1 
 
Required- Solid Tumor or Bone Marrow Core Biopsy (only if solid tumor is 
not available)- You will be provided a kit for tumor collection.  This kit will 
include instructions, collection tubes containing RNA later (place tumor biopsy 
here within 20 minutes of harvest), and shipping instructions. Follow collection 
instructions (also listed in Appendix II) and ship overnight at ambient 
temperature to: 
 
 
Clinical Reference Laboratory 
Attn: Molecular  
11711 W. 83rd Terrace 
Lenexa, KS 66214 
Phone: 913-492-3652 
 
 
 
 
 
 
 
 
 

 
 
 
 
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2. Sample 2- Required Tumor Sample for DNA Mutation Panel: 
 
Add tumor or needle core biopsy to cryo-vial, snap freeze and ship on at least 1kg of 
dry ice to: 
Spectrum Health Molecular Diagnostics 
145 Michigan St Ne Ste 6201 
Lemmen-Holton Cancer Pavilion 
Grand Rapids, Michigan 
49503-2566 
Ph: 616-486-6264 
 
9.3.1.2 Send the following Recommended secondary tumor samples along with appropriate 
forms listed in order of priority (please work your way down the list of tumor samples 
until you either run out of available sample or have completed all samples. Once this 
occurs move on to Bone Marrow samples: 
 
 
You will be provided a kit for tumor collection (fresh snap frozen and in culture 
media).  This kit will include instructions, collection tools, shipping box, and 
shipping instructions. Follow collection instructions and ship as directed overnight.  
 
3. Sample 3: 
 
With sterile technique and within 20 minutes add tumor sample or needle core biopsy 
to T25 flask containing cell growth media (provided), seal with parafilm, and 
overnight at ambient temperature to: 
Ping Zhao  
Neuroblastoma Translational Research Laboratory  
Coopers Landing 
1345 Monroe Ave 
Grand Rapids, MI 49503  
Ping.zhao@helendevoschildrens.org 
 
4. Sample 4: 
 
Add tumor or needle core biopsy to cryo-vial, snap freeze and ship on at least 1kg of 
dry ice to: 
Ping Zhao  
Neuroblastoma Translational Research Laboratory  
Coopers Landing 
1345 Monroe Ave 
Grand Rapids, MI 49503  
Ping.zhao@helendevoschildrens.org 
 
 
 

 
 
 
 
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5. Sample 5: 
Add tumor or needle core biopsy to cryo-vial, snap freeze and ship on at least 1kg of 
dry ice to: 
Ping Zhao  
Neuroblastoma Translational Research Laboratory  
Coopers Landing 
1345 Monroe Ave 
Grand Rapids, MI 49503  
Ping.zhao@helendevoschildrens.org 
 
6. Sample 6: 
Add tumor or needle core biopsy to RNA Later and ship overnight at ambient 
temperature to: 
Ping Zhao  
Neuroblastoma Translational Research Laboratory  
Coopers Landing 
1345 Monroe Ave 
Grand Rapids, MI 49503  
Ping.zhao@helendevoschildrens.org 
 
7. Sample 7: 
Add tumor or needle core biopsy to cryo-vial, snap freeze and ship on at least 1kg of 
dry ice to: 
Ping Zhao  
Neuroblastoma Translational Research Laboratory  
Coopers Landing 
1345 Monroe Ave 
Grand Rapids, MI 49503  
Ping.zhao@helendevoschildrens.org 
 
9.3.1.3 For all Tumor Types: Send the following Recommended secondary blood samples 
listed in order of priority (along with appropriate forms): 
 
Blood-  Send 4-6 ml of blood in  tubes (tubes and instructions will be provided). 
1. Sample 8: 
Send blood in EDTA tube (ambient) to: 
DORRANCE CLINICAL LABORATORY at TGen 
445 N 5th Street, Suite 400 
Phoenix, AZ 85004 
Phone: 602-343-8796  
Lab Fax: 602-343-8545 
 
 
 

 
 
 
 
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2. Sample 9: 
Send PAX DNA Gene tubes (ambient) to: 
 
Ping Zhao 
Neuroblastoma Translational Research Laboratory  
Coopers Landing 
1345 Monroe Ave 
Grand Rapids, MI 49503  
Ping.zhao@helendevoschildrens.org 
 
9.3.1.4 For Neuroblastoma Subjects or Any subject with suspected bone marrow disease 
Only- Send the following Recommended secondary bone marrow samples listed in 
order of priority (along with appropriate forms): 
 
Bone Marrow Aspirate- Send 4cc of bilateral bone marrow in green top (sodium 
heparin) tube(s) priority overnight at room temperature to: 
 
1. Sample 10: 
Send bone marrow aspirate ambient to: 
 
Pam Kidd, MD 
Spectrum Health Flow Cytometry Lab 
145 Michigan St Ne Ste 6201 
Lemmen-Holton Cancer Pavilion 
Grand Rapids, Michigan 
49503-2566 
Ph: 616-486- 6270 
 
 
2. Sample 11: 
Send bone marrow aspirate ambient to: 
(Please alert site 2-3 days prior to procedure.  Contact site to confirm shipment as 
well.) 
 
Ping Zhao  
Neuroblastoma Translational Research Laboratory  
Coopers Landing 
1345 Monroe Ave 
Grand Rapids, MI 49503  
Ping.zhao@helendevoschildrens.org 
 
 
 
 
 
 

 
 
 
 
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Notes:  If all samples are collected, you will be collecting 11 samples and mailing 6 
packages.  The samples above are listed in decreasing priority (1-11) 
 
* Sample 1 to CRL (ambient) 
** Sample 2 to Spectrum Health Molecular Diagnostics (frozen) 
***Sample 3, 6, 9, & 11 to VIA (ambient). 
****Samples 4, 5 & 7 to VIA (frozen). 
***** Sample 8 to TGen (ambient) 
****** Sample 10 to Spectrum Health Flow (ambient) 
 
******* Keep all collection tubes at 4 degrees until ready to use. 
 
Please contact Ping Zhao if you have any trouble with the preparation or packaging of the 
samples.   Ping.zhao@helendevoschildrens.org 
 
 
9.3.2 For Neuroblastoma Subjects or Any subject with suspected bone marrow disease 
Only- Sample Procurement and Shipping at the end of Cycle 2 and every two cycles 
after that:   
 
 
Send the following Recommended samples to Spectrum Health (Priority if limited 
samples- First): 
 
1. Bone Marrow Aspirate- Send 2cc of bilateral bone marrow in green top (sodium 
heparin) tube(s) priority overnight at room temperature to: 
 
Flow Cytometry Lab of Spectrum Health  
Attn: Pam Kidd, MD 
Lemmen-Holton Cancer Pavilion   
145 Michigan Street  NE Suite 6201 
Grand Rapids, MI 49503 
Ph: 616-486- 6270 
 
Send the following Recommended samples (along with appropriate forms) to the  
Neuroblastoma Translational Research Laboratory   (Priority if limited samples- 
Second) 
 
2. Bone Marrow Aspirate- Send 4cc of bilateral bone marrow in green top (sodium 
heparin) tube(s) priority overnight at room temperature to: 
 
Ping Zhao  
Neuroblastoma Translational Research Laboratory  
Coopers Landing 
1345 Monroe Ave 
Grand Rapids, MI 49503  
Ping.zhao@helendevoschildrens.org 
 
 

 
 
 
 
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9.4 
Correlative Biology Studies 
 
At the Neuroblastoma Translational Research Laboratory  tumor cells (from either biopsy 
or bone marrow samples) will be grown to 70% confluency in neurobasal media with 
EGF and FGF. Cell lines will be maintained in culture for these and future biology 
studies. These will include studies such as determining the growth curves and 
responsiveness of cells derived from these tumors to a variety of agents identified on the 
report in vitro (both the chosen regimen as well as alternate options). Cells will be 
injected into the inguinal fat pad of NOD SCID mice for generation of subject xenografts. 
These mice will be used for correlative drug testing experiments based on predictive 
models. Evaluation of mechanism of action of new drug combinations will be evaluated 
in mice models through immunohistochemical staining, western blotting, and RNA 
expression profiling of tumor preps. These models will allow us the opportunity validate 
predictive modeling in a laboratory model. 
 . 
 
Samples will be sent to the Translational Genomics Institute (TGen) for DNA and RNA 
sequencing. Isolation of DNA and RNA from subject samples will be performed for use 
in genomic studies. Nucleic acids will be extracted from blood, bone Marrow or tumor 
tissues.  Analysis for mutations or Single Nucleotide Variants (SNVs) in tumors, using 
germ line DNA as control, will be conducted using blood and fresh or frozen tumor 
tissue.  Comparative Genomics Hybridization, whole genome sequencing of tumor and 
germline DNA, messenger RNA sequencing and expression analysis and epigenentic 
studies including whole methylome analysis using next generation sequencing may be 
performed.  
 
Bone marrow samples will also be sent to Spectrum Health to be sorted by flow 
cytometry using the immunophenotyping six-color, ganglioside GD2, analysis using 
monoclonal antibodies to membrane antigen expression of ganglioside GD2FITC dye, 
CD81FITCdye, the absence of CD45PerCPdyeleukocytic antigen, and the presence of 
CD56APC NCAM antigen, CD9, and/or CD34.  Cells or tumor samples will have RNA 
isolated and run on an Affymetrix U133+ Array chip. Data will be analyzed for 
comparison of bone marrow tumor and solid tumor expression profiles. 
9.5 
Storage 
 
Blood and tumor samples collected for any studies performed in this protocol, and any 
other components from the processed cells, may be stored indefinitely to research 
scientific questions related to cancer and/or study drugs. The subject retains the right to 
have the sample material destroyed at any time by contacting the principal investigator. 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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9.6 
Plan for Communication of Samples and Data 
 
 

 
 
 
 
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9.7 
Plan for Communication of Collaborating Sites 
Communication between centers will be critical in this trial.  Prior to consent of the subject, the 
NMTRC research coordinator will be contacted (via e-mail). If a spot is available at the time, the 
potential subject will undergo consent and completion of all required screening procedures and 
certification of all inclusion and exclusion criteria by the Investigator.  If the subject fits all 
enrollment criteria, the site will again contact the coordinator at the NMTRC who will notify the 
Clinical Reference Laboratory, Spectrum Health, Neuroblastoma Translational Research 
Laboratory , TGen, and Intervention Insights in preparation for collection and processing of tissue 
sample. The research coordinator at NMTRC will organize the convening of members of the 
tumor board for discussion of the current case once the full report is available. In addition, a study 
enrollment form will be faxed to the coordinator at NMTRC, a unique subject identifier will be 
assigned and the enrollment form will be sent back to the participating site. The NMTRC will 
contact all sites via e-mail if the study enrollment is on hold or closed at any time. 
 
Subject samples will be collected at each institution and follow the flow chart above.  Once the 
reports are generated they will be sent to NMTRC/Dr. Sholler. The Principal Investigator 
enrolling the patient will prepare a tumor board presentation. The presentation and reports will be 
sent to all tumor board members by the NMTRC coordinator.  There will be a meeting of the 
tumor board within 4 days of receiving the report to decide on the treatment plan 
recommendation. The recommendation will be reviewed in depth for safety by the Pharmacist. 
The treatment plan and memo will be discussed with the subject and their parents and upon their 
signed agreement the treatment will begin within 1 week of the discussion with parents.   
  
 
Each site will also participate in a 1 hour monthly video or teleconference meeting to review 
study progress and subjects currently enrolled. There will also be a yearly face-face study 
committee meeting hosted by a member institution. 
 
10 ADVERSE EVENT REPORTING 
10.1 
 Definitions 
10.1.1 Adverse Event 
An adverse event is any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have to have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding, for example), symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. 
An untoward medical event which occurs outside the period of follow-up as defined in the 
protocol will not be considered an adverse event unless related to study drug.  Worsening of a 
medical condition for which the efficacy of the study drug is being evaluated will not be 
considered an adverse event.  
 
10.1.2 Unexpected Adverse Event 
An unexpected adverse event is one for which the nature or severity of the event is not consistent 
with the applicable product information as outlined in package insert filed with the FDA. 
 

 
 
 
 
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10.1.3 Serious Adverse Event 
A serious adverse event is any untoward medical occurrence that: 
• 
Results in death 
• 
Is life-threatening (an event in which the subject was at risk of death at the time of the 
event; it does not refer to an event which hypothetically might have caused death if it were 
more severe) 
• 
Requires in-patient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant disability/incapacity 
 
• 
Results in a congenital anomaly or birth defect 
• 
Other important medical events that may not be immediately life-threatening or result in 
death or hospitalization but may jeopardize the subject or may require intervention to 
prevent one of the other outcomes listed above.  Examples of such events are intensive 
treatment in an emergency room for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; or development of drug dependency or 
drug abuse. 
 
The term “severe” is often used to describe the intensity (severity) of an event; the event itself 
may be of relatively minor medical significance (such as a severe headache).  This is not the same 
as “serious”, which is based on subject/event outcome or action criteria usually associated with 
events that pose a threat to a subject’s life or functioning.    
10.1.4 Documenting Adverse Events  
The Investigator should elicit information regarding the occurrence of adverse events through 
open-ended questioning of the subject, physical examination and review of laboratory results.   
 
All adverse events, whether serious or not, will be described in the source documents and Grade 2 
or higher (per CTCAE 4.0) adverse events that occur while on study should be captured on the 
adverse event case report form.  All Baseline AE’s will be captured on a separate baseline 
Adverse event case report form. All Grade 2 or higher new events, as well as those that worsen in 
intensity or frequency relative to baseline, which occur after administration of study drug through 
the period of protocol-specified follow-up, must be captured. 
 
Information to be reported in the description of each adverse event includes: 
• 
A medical diagnosis of the event (if a medical diagnosis cannot be determined, a 
description of each sign or symptom characterizing the event should be recorded)  
• 
The date of onset of the event and relatedness to treatment regimen. 
• 
The date of resolution of the event and whether the event is serious or not 
• 
Action taken; drug treatment required; non-drug treatment required; hospitalization or 
prolongation of hospitalization required; diagnostic procedure performed; subject 
discontinued from the study 
• 
Outcome: complete recovery or return to baseline; unknown/lost to follow-up; adverse 
event persisting; subject died (notify the NMTRC immediately)   
 
Adverse events, regardless of suspected cause, will be collected for 30 days following the last 
treatment, suspected study drug-related toxicity at the 30 day follow-up visit must continue to be 
followed until resolution to baseline or  ≤ Grade 2 or stabilization of the event. 
 

 
 
 
 
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10.1.5 Expedited Reporting of Serious Adverse Events 
All fatal or life–threatening adverse events must be reported to the NMTRC immediately by 
telephone, fax, or e-mail within 24 hours of knowledge of the event. If full information is not 
known, additional follow-up by the Investigator will be required. 
 
All other serious adverse events that are unexpected (not listed in the relevant appendices) which 
occur any time after the subject has been consented up to 30 days after the last dose of treatment, 
and are possibly probably, or definitely related to the research must be reported to the study chair 
and appropriate regulatory authorities (local IRB and FDA if required) within 7 days of 
notification of the event. 
 
All Grade 3 and 4 (CTCAE), events that are not in the relevant appendices and that are possibly, 
probably, or definitely related to the research, but are not included in the SAE category above 
should also be reported to the study chair and appropriate regulatory authorities within 7 days of 
notification of the event. 
 
The Investigator must report all serious adverse events reported to regulatory authorities in an 
expedited manner to the local IRB or IEC.  All serious adverse events must be followed until 
resolution or stabilization.   Unanticipated problems involving risk to subjects or others, serious 
adverse events related to participation in the study, and all volunteer deaths related to 
participation in the study should be promptly reported to the NMTRC. 
 
 
10.1.6 Grading and Relatedness of Adverse Events 
10.1.6.1 Grading of Severity of an Adverse Event 
Each adverse event (Grade 2 or higher) will be graded for severity per the National Cancer 
Institute Common Terminology Criteria for Adverse Events (CTCAE V 4.0), and these criteria 
must be used in grading the severity of adverse events.  The criteria can be found at: 
http://ctep.cancer.gov/reporting/ctc.html. 
 
Grading of Severity of an Adverse Event Not Listed in Published Criteria: 
For those adverse events which are not listed as part of the NCI CTCAE V 4.0, the same grading 
system should be used, where: 
• 
Mild corresponds to an event not resulting in disability or incapacity and which resolves 
without intervention 
• 
Moderate corresponds to an event not resulting in disability or incapacity but which 
requires intervention 
• 
Severe corresponds to an event resulting in temporary disability or incapacity and which 
requires intervention 
• 
Life-threatening corresponds to an event in which the subject was at risk of death at the 
time of the event 
• 
Fatal corresponds to an event that results in the death of the subject 
 

 
 
 
 
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10.1.6.2 Relatedness to Study Drug 
The Investigator must attempt to determine if an adverse event is in some way related to the use 
of the study drug and define an attribution category. This relationship should be described as 
follows: 
 
RELATIONSHIP 
ATTRIBUTION 
DESCRIPTION 
Unrelated to 
investigational 
agent/intervention 
 
Unrelated 
The AE is clearly NOT related to the 
intervention. 
The event is clearly due to causes distinct from the use of 
the study drug, such as a documented pre-existing 
condition, the effect of a concomitant medication, or a new 
condition which, based on the pathophysiology of the 
condition, and the pharmacology of the study drug, would 
be unrelated to the use of the study drug. 
Unlikely 
The AE is doubtfully related to the intervention. 
Adverse event does not have temporal relationship to 
intervention, could readily have been produced by the 
subject’s clinical state, could have been due to 
environmental or other interventions, does not follow 
known pattern of response to intervention, does not 
reappear or worsen with reintroduction of intervention. 
Related to 
investigational 
agent/intervention 
 
Possible 
The AE may be related to the intervention. 
The event follows a reasonable temporal sequence from 
administration of the study drug and the event follows a 
known response pattern to the study drug BUT the event 
could have been produced by an intercurrent medical 
condition which, based on the pathophysiology of the 
condition, and the pharmacology of the study drug, would 
be unlikely related to the use of the study drug OR the 
event could be the effect of a concomitant medication. 
Probable 
The AE is likely related to the intervention. 
The event follows a reasonable temporal sequence from 
administration of the study drug, the event follows a 
known response pattern to the study drug AND the event 
cannot have been reasonably explained by an intercurrent 
medical condition OR the event cannot be the effect of a 
concomitant medication. 
Definite 
The AE is clearly related to the intervention. 
The event follows a reasonable temporal sequence from 
administration of the study drug, the event follows a 
known response pattern to the study drug and based on the 
known pharmacology of the study drug, the event is 
clearly related to the effect of the study drug.  The adverse 
event improves upon discontinuation of the study drug and 
reappears upon repeat exposure. 
 
 
 
 

 
 
 
 
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11 SUBJECT WITHDRAWAL AND TRIAL DISCONTINUATION 
11.1 
Criteria for Subject Off-Therapy 
Subjects will be removed from the study therapy for the following reasons: 
• 
Progressive neoplastic disease 
• 
Subject or guardian withdraws consent to continue in the trial 
• 
Subject develops an intercurrent illness that precludes further participation, or requires a 
prohibited concomitant treatment 
• 
The Investigator withdraws the subject in the subject’s best interests 
• 
Subject is lost to follow-up (defined as the inability to contact the subject on 3 separate 
occasions over a period of 2 weeks) 
• 
Administrative reasons (e.g., the subject is transferred to hospice care) 
• 
An adverse event, which in the opinion of the Investigator, precludes further trial 
participation or fulfills the protocol requirements for withdrawal  
• 
Death 
 
11.2 
Criteria for Subject Off-Study 
Subjects may be withdrawn from the study completely which includes withdrawal from survival 
follow-up for the following reasons: 
• 
Completion of all study requirements 
• 
Subject or guardian withdraws consent to continue in the trial (if this occurs, no further 
study visits or data may be collected) 
• 
Subject is lost to follow-up (defined as the inability to contact the subject on 3 separate 
occasions over a period of 2 weeks) 
• 
Death 
 
11.3 
Trial Discontinuation  
The Neuroblastoma and Medulloblastoma Translational Research Consortium (NMTRC) may 
discontinue the trial as a whole or at an individual investigational site at any time. Reasons for 
early trial discontinuation may include, but are not limited to, unacceptable toxicity of 
treatment regimens, a request to discontinue the trial from a regulatory authority, protocol 
violations at an investigational site, violations of good clinical practice at an investigational 
site, or poor enrollment. The NMTRC will promptly inform all Investigators in the event of 
premature study discontinuation and provide all Investigators with instructions regarding the 
disposition of subjects still on study. Should the study be terminated prematurely, all case 
report forms and any other study material will be returned to the NMTRC.  
 
12 DATA ANALYSIS   
12.1 
Data Quality Assurance  
Electronic and paper case report forms will be checked for correctness against source document 
data by the independent study monitor. If any entries into the CRF are incorrect, incomplete or 
illegible, the study monitor will ask the Investigator or the study site staff to make appropriate 
corrections.  

 
 
 
 
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12.2 
Data Safety Monitoring Board (DSMB)  
An independent Data Safety and Monitoring Board (DSMB) will oversee the conduct of the 
study. The members of this Board will receive database summaries, including adverse event 
reports, and will convene either in person or via teleconference according to section 3.5. The 
Board will be responsible for decisions regarding possible termination and/or early reporting of 
the study.  
12.3 
Process and Feasibility Analysis 
Each of the process measures including the total time to treatment initiation and time to 
completion of the first cycle of treatment will be described using standard descriptive methods 
such as means, medians, standard deviations, and 95% confidence intervals.  The total time 
duration to treatment initiation and time to completion of the first cycle of treatment will also be 
examined using Kaplan-Meier plots since some patients who are considered process failures or 
who do not complete the full duration to the completion of the first cycle of treatment may 
contribute censored data.  The formal hypothesis testing of the feasibility or success is based upon 
the 2-stage Mini-Max testing process outlined in Section 8: Sample Size Justification.  Further 
quantification of the feasibility success rate will be based upon the percentage of the n = 16 
patients in each strata who achieve the specified overall time frame limits.  This success rate will 
supplemented with an exact 95% confidence interval using a Binomial distribution model due to 
the small sample size involved.  
12.4 
Secondary Data Analysis 
Overall response rates (ORR) will be examined using rates for each of the clinical response 
categories supplemented using exact 95% confidence intervals.  Progression free survival (PFS) 
data for each of the three clinical strata will be examined using Kaplan-Meier time to event plots.  
Differences in the PFS for the current treatment protocol with historical PFS values will be 
explored using Cox proportional hazard rate methods when possible. 
 
13 ADMINISTRATIVE PROCEDURES  
13.1 
Subject Informed Consent  
No study related procedures will be performed until a subject or a subject’s legal representative 
has given written informed consent. The NMTRC will provide the site Investigators with a 
sample informed consent document that conforms to all the requirements for informed consent 
according to ICH GCP and US FDA guidelines (21 CFR 50). However, it is up to each site 
Investigator to provide a final informed consent that may include additional elements required by 
the Investigator’s institution or local regulatory authorities. The IRB/EC for each investigational 
site must approve the consent form document prior to study activation; changes to the consent 
form during the course of the study may also require IRB/EC approval. The informed consent 
document must clearly describe the potential risks and benefits of the trial, and each prospective 
participant must be given adequate time to discuss the trial with the Investigator or site staff and 
to decide whether or not to participate. Each subject who agrees to participate in the trial and who 
signs the informed consent will be given a copy of the signed dated and witnessed document. The 
original copy of the signed, dated and witnessed informed consent document will be retained by 
the Investigator in the study files. After the tumor board has made a therapy decision and that 
decision has been reviewed by the pharmacist, a therapy specific treatment memo will be signed. 
 

 
 
 
 
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The Investigator must also obtain authorization from the subject to use and/or disclose protected 
health information in compliance with the Health Insurance Portabiltiy and Accountability Act 
(HIPAA). Written HIPAA authorization may be obtained as part of the informed consent process.  
 
13.2 
Ethical Conduct of the Study and IRB/IEC Approval  
The study will be conducted according to the principles of the 2004 version of the Declaration of 
Helsinki, the International Conference on Harmonization Guidance on Good Clinical Practice and 
the requirements of all local regulatory authorities regarding the conduct of clinical trials and the 
protection of human subjects.  
 
The Investigator will submit the protocol, the informed consent and any other material used to 
inform subjects about the trial to the local IRB/IEC for approval prior to enrolling any subject 
into the trial. The IRB/IEC should be duly constituted according to applicable regulatory 
requirements. Approval must be in the form of a letter signed by the Chairperson of the IRB/IEC 
or the Chairperson’s designee, must be on IRB/IEC stationary and must include the protocol by 
name and/or designated number. If an Investigator is a member of the IRB/IEC, the approval 
letter must stipulate that the Investigator did not participate in the final vote, although the 
Investigator may participate in the discussion of the trial. The Investigator will also inform the 
IRB/IEC of any serious adverse events that are reported to regulatory authorities and will provide 
to the IRB/IEC a final summary of the results of the trial at the conclusion of the trial.  
 
Any amendments to the protocol will be done through the NMTRC, and will be submitted to the 
coordinating IRB/IEC for review and written approval before implementation.  
 
13.3 
Monitoring  
An independent study monitor will make regularly scheduled trips to the investigational site to 
review the progress of the trial. The actual frequency of monitoring trips will depend on the 
enrollment rate and performance at each site. At each visit, the monitor will review various 
aspects of the trial including, but not limited to, screening and enrollment logs; compliance with 
the protocol and with the principles of Good Clinical Practice; completion of case report forms; 
source data verification; facilities and staff.  
 
During scheduled monitoring visits, the Investigator and the investigational site staff must be 
available to meet with the study monitor in order to discuss the progress of the trial, make 
necessary corrections to case report form entries, respond to data clarification requests and 
respond to any other trial-related inquiries of the monitor.  
 
In addition to the above, representatives of the NMTRC or government inspectors may review the 
conduct/results of the trial at the investigational site. The Investigator at each site must promptly 
notify the NMTRC of any audit requests by regulatory authorities.  
 
A separate monitoring plan will be provided for additional monitoring guidelines.  
 

 
 
 
 
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13.4 
Pre-Study Documentation  
Prior to initiating the trial, the Investigators at each site will provide to the NMTRC the following 
documents:  
• A signed NMTRC008 Investigator Agreement Form 
• A current curriculum vitae for the Principal Investigator and each sub-investigator listed on the 
Investigator Agreement Form 
• A copy of the Investigator’s medical license from the state in which the study is being 
conducted 
• A letter from the IRB or EC stipulating approval of the protocol, the informed consent 
document and any other material provided to potential trial participants with information about 
the trial (e.g., advertisements)  
• A copy of the IRB- or EC-approved informed consent document  
• Current IRB membership list for IRB’s without a multiple project assurance number or an IRB 
organization number under the Federal Wide Assurance program (www.ohrp.osophs.dhhs.gov).  
• A signed Investigator Signature Sheet for each amendment put through local IRB- Found on 
page 9 of this protocol (original) 
• A completed conflict of interest and financial disclosure form (copy of original) from each 
person listed in the Investigator Agreement Form.  
• Current laboratory certification for the reference laboratory  
• A list of current laboratory normal values for the reference laboratory  
13.5 
Confidentiality  
It is the responsibility of the investigator to insure that the confidentiality of all subjects 
participating in the trial and all of their medical information is maintained. Case report forms and 
other documents submitted must never contain the name of a trial participant. Each subject in the 
trial will be identified by a unique identifier that will be used on all CRF’s and any other material 
submitted to the NMTRC. Case Report Forms for this study will be both paper and electronic. 
Electronic data will be stored in a HIPAA compliant data center. All case report forms and any 
identifying information must be kept in a secure location with access limited to the study staff 
directly participating in the trial.  
 
Personal medical information may be reviewed by representatives of the NMTRC, of the IRB or 
of regulatory authorities in the course of monitoring the progress of the trial. Every reasonable 
effort will be made to maintain such information as confidential.  
 
The results of the study may be presented in reports, published in scientific journals or presented 
at medical meetings; however, subject names will never be used in any reports about the study.  
 
13.6 
Source Documents  
The Investigator will maintain records separate from the case report forms in the form of clinical 
charts, medical records, original laboratory, radiology and pathology reports, pharmacy records, 
etc. The Investigator will document in the clinic chart or medical record the name and number of 
the trial and the date on which the subject signed informed consent prior to the subject’s 
participation in the trial. Source documents must completely reflect the nature and extent of the 
subject’s medical care, and must be available for source document verification against entries in 

 
 
 
 
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the case report forms when the monitor visits the investigational site. All information obtained 
from source documents will be kept in strict confidentiality.  
 
13.7 
Record Retention  
The Investigator will retain the records of the study for 15 years.  The NMTRC will notify 
Investigators when retention of study records is no longer required. All study records must be 
maintained in a safe and secure location that allows for timely retrieval, if needed.  
 
Study records that must be retained include copies of case report forms, signed informed 
consents, correspondence with the IRB or IEC, source documents, clinic charts, medical records, 
laboratory results, radiographic reports and screening/enrollment logs.  
 
Should the Investigator relocate or retire, or should there be any changes in the archival 
arrangements for the study records, the NMTRC must be notified. The responsibility for 
maintaining the study records may be transferred to another suitable individual, but the NMTRC 
must be notified of the identity of the individual assuming responsibility for maintaining the study 
records and the location of their storage. 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Lamb, J., et al., The Connectivity Map: using gene-expression signatures to 
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Staunton, J.E., et al., Chemosensitivity prediction by transcriptional profiling. 
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Furge, K.A., et al., Identification of deregulated oncogenic pathways in renal cell 
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Warzynski, M.J., et al., Flow cytometric immunophenotyping test for 
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Gheeya, J.S., et al., Screening a panel of drugs with diverse mechanisms of action 
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Katoh, M., FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer 
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Schultz, K.R., T. Prestidge, and B. Camitta, Philadelphia chromosome-positive 
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Klener, P. and P. Klener, Jr., [ABL1, SRC and other non-receptor protein tyrosine 
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Keam, S.J., Dasatinib: in chronic myeloid leukemia and Philadelphia 
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Mootha, V.K., et al., PGC-1alpha-responsive genes involved in oxidative 
phosphorylation are coordinately downregulated in human diabetes. Nat Genet, 
2003. 34(3): p. 267-73. 
62. 
Dezso, Z., et al., Identifying disease-specific genes based on their topological 
significance in protein networks. BMC Syst Biol, 2009. 3: p. 36. 
63. 
Subramanian, A., et al., Gene set enrichment analysis: a knowledge-based 
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64. 
Pohlers, D., et al., Constitutive upregulation of the transforming growth factor-
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2007. 9(3): p. R59. 
 
 
 
 
 
 
 
 

 
 
 
 
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Appendix I: Performance Status/Scores 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Appendix II: Biology Studies Collection and Shipping forms 
Instructions for Core/Needle Biopsy Specimens 
Interventional Radiologist: 
       Intervention Insights Sample 
1. Obtain first core biopsy (if possible; otherwise 2nd core) 
a. At least 19 gauge guiding needle or larger in caliber 
b. Remove excess blood from the sample with sterile saline rinse (provided 
in the kit) without damaging the sample 
 
2. DO NOT PLACE SAMPLE INTO FORMALIN. Place sample into the tube 1 
containing RNA Later provided by the NTMRC. Note time of extraction and 
placement into tube on Form A  
 
       Standard Pathology Sample 
3. Obtain second core biopsy from same track according to institutional protocol 
 
4. Place core (for standard pathology) in neutral buffered formalin container per 
standard practices 
 
5. Please fill out the Intervention Radiologist section of Form A; send all forms and 
all tissue to pathology 
Pathologist: 
1. Please complete the Pathologist section of Form A 
 
2. Place the Tube 1 with the patient sample and Form A in the shipping kit.  Affix 
the label to FedEx shipping bag in the kit and place the kit in the bag for 
shipment.  Please ship via FedEx (if you do not have a scheduled FedEx pickup, 
call 800-GO-FEDEX - 800-463-3339) 
 
3. Please hold Form B until the processing is complete for the Standard Pathology 
Sample.  Upon the generation of a pathology report, please fill out Form B and 
fax both the pathology report and Form B to the NMTRC at 1-616-233-8934 (fax).   
Note- CRL is unable to generate a patient OncInsights molecular 
report for the patient’s physician without the completion of Form B 
- Thank you  
For questions please call the NMTRC at (616) 267-0326 or e-mail emily.arndt@vai.org 

 
 
 
 
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Instructions for Incision/Excision Surgery Specimen 
Surgeon: 
1. Obtain surgical excision/biopsy (operating room or office) 
a. DO NOT PLACE SAMPLE INTO FORMALIN 
b. Please wrap in sterile gauze soaked with the provided sterile saline (0.9% 
NaCl without dextrose), place in a labeled container and note time of 
extraction on container label 
 
2. Send to Pathology/Histology ASAP; please hand deliver to pathology within 20 
minutes 
Pathologist/Pathology Assistant: 
1. Do not ink specimen (prior to completing steps 2-4 below) 
 
2. Section specimen with a sterile blade on a clean surface.  Select tumor tissue 
that appears non-necrotic; avoid normal tissue.  Obtain a sample with a 
maximum dimension of 0.5 cm3 (approximately the size of a pencil eraser) 
 
3. Place dissected sample in the tube filled with RNA Later provided by the NMTRC 
labeled Tube 1.  Note time on Form A (Pathology) 
 
4. Place Tube 1 with the patient sample and Form A (Pathology) in the shipping 
box.  Affix a shipping label to the FedEx shipping bag and place the kit in the bag 
for shipment.  Please ship via FedEx (if you do not have a scheduled FedEx 
pickup, call 800-GO-FEDEX - 800-463-3339) 
 
5. Obtain a second specimen for histopathological analysis at your institution, 
adjacent to the initial specimen, again avoiding normal or necrotic tissue.  
Handle any remaining tissue as per your institutional protocols and in 
accordance with physician order 
 
6. Please hold Form B until the processing is complete for the Standard Pathology 
Sample.  Upon the generation of a pathology report, please fill out Form B and 
fax both the pathology report and Form B to the NMTRC at 1-(616) 267-1005 
(fax).   
 Note- CRL is unable to generate a patient OncInsights molecular 
report for the patient’s physician without the completion of Form B  
For questions please call the NMTRC at (616) 267-0326  or e-mail emily.arndt@vai.org 

 
 
 
 
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Appendix III: Pharmacopeia Library 
Drug Table: 
acarbose 
chlorambucil 
ethosuximide 
pemetrexed 
acetazolamide 
chlorothiazide 
etodolac 
pentamidine 
acetylsalicylic acid 
chlorproMAZINE 
etoposide (Vepesid) 
pentostatin 
adalimumab 
chlorproPAMIDE 
everolimus 
phentolamine 
albendazole 
chlorzoxazone 
famotidine 
piperazine 
aldesleukin 
ciclosporin 
felbamate 
piroxicam 
alprazolam 
ciprofloxacin 
felodipine 
pravastatin sodium 
amantadine 
cisplatin 
Fenoprofen 
prazosin hydrochloride 
ambenonium chloride 
citalopram 
fexofenadine 
prednisoLONE 
amikacin 
clemastine 
flucytosine 
prochlorperazine 
amiloride hydrochloride 
clindamycin 
fludarabine 
propylthiouracil 
aminocaproic acid 
clofarabine 
fludrocortisone 
pyridostigmine bromide 
amitriptyline hydrochloride 
clofibrate 
fluoxetine 
rabeprazole sodium 
amoxapine 
clomipramine 
fluvastatin 
raloxifene hydrochloride 
amoxicillin 
clonidine 
fluvoxamine 
ramipril 
ampicillin 
clopidogrel 
folic acid 
reserpine 
anakinra 
clotrimazole 
furosemide 
Rifamycin 
anastrozole 
clozapine 
gabapentin 
Rituxumab 
ascorbic acid 
colchicine 
gefitinib 
romidepsin 
atorvastatin 
cortisone 
gemcitabine 
rosiglitazone maleate 
atovaquone 
crizotinib 
gentamicin 
rosuvastatin calcium 
azacitidine 
cyanocobalamin 
griseofulvin 
Saha 
azathioprine 
cyclophosphamide 
guaifenesin 
simvastatin 
aztreonam 
cycloserine 
guanfacine 
sirolimus (rapamycin) 
baclofen 
cyclosporin 
hydroxyurea 
sodium phenylbutyrate 
balsalazide 
cyproheptadine 
ibuprofen 
sorafenib 
BCNU 
Cytarabine (Ara-C) 
imatinib 
sulfasalazine 
betamethasone 
dacarbazine 
indomethacin 
sulindac 
bevacizumab 
dantrolene 
irinotecan 
sulindac sulfide 
biotin 
dapsone 
ixabepilone 
sunitinib malate 
bisacodyl 
dasatinib 
ketoprofen 
Sunitinib 
bortezomib (velcade) 
DAUNOrubicin 
ketorolac 
tacrolimus 
bromocriptine 
decitabine 
lansoprazole 
tamoxifen 
brompheniramine 
deferoxamine 
Lapatinib 
Tarceva 
budesonide 
demecolcine sodium 
leflunomide 
temsirolimus 
bumetanide 
dexamethasone 
lenalidomide 
temozolomide 
bupropion 
dextromethorphan 
lovastatin 
thalidomide 
buspirone 
diazoxide 
megestrol 
theophylline 
calcitriol 
diclofenac 
mercaptopurine 
thioguanine 
captopril 
dicloxacillin 
mesalamine 
thioridazine 
hydrochloride 
carbamazepine 
diltiazem 
metformin 
Thio-tepa 
carbidopa/Levodopa 
diphenhydramine 
methimazole 
TOLBUTamide 
carbinoxamine 
dipyridamole 
methotrexate 
tolcapone 

 
 
 
 
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carboplatin 
disopyramide 
Methyl CCNU 
tolmetin 
CCNU 
docetaxel 
minocycline 
topiramate 
cefaclor 
donepezil hydrochloride 
mitoxantrone 
topotecan 
cefadroxil 
DOXOrubicin 
nabumetone 
torsemide 
cefazolin 
doxycycline 
naproxen 
tranylcypromine 
cefepime 
droperidol 
navelbine 
trastuzumab 
cefotaxime 
enalapril 
nitisinone 
trazodone 
cefotetan 
epirubicin 
omeprazole 
tretinoin 
cefoxitin 
ergocalciferol 
orlistat 
valproic acid 
ceftazidime 
erlotinib 
oxaliplatin 
vandetanib 
cefuroxime 
erythromycin 
oxaprozin 
verapamil 
celecoxib 
Estradiol 
paclitaxel 
vinBLAStine 
cetirizine 
ethacrynic acid 
pamidronate 
vinorelbine 
cetuximab 
ethambutol 
Pazopanib 
vorinostat 
 
ethionamide 
Peg-asparaginase 
zolendronic acid 
 
 
When referenced:  
Frequency of Side Effects 
Likely/Common = 21 to 100 subjects per 100 subjects 
Less Likely = 1 to 20 subjects per 100 subjects 
Rare but Serious = 1 to 4 subjects per 100 subjects 
 
Acarbose 
 
Common 
Rare (<1%) 
Diarrhea (31%) 
Flatulence (74%) 
Abdominal pain or distention (19%) 
Erythema 
Exanthema 
urticaria 
Hypoglycemia  
lipid abnormalities 
Bowel obstruction 
Anemia 
Hepatotoxicity 
Elevated liver enzymes 
right upper quadrant pain 
dark urine 
jaundice 
hepatomegaly 
light-colored stools 
sleepiness 
weakness 
dizziness 
headache  
vertigo 
 
• 
Instruct patient about signs/symptoms of hypoglycemia if patient is on concurrent 
antidiabetic medicine. 

 
 
 
 
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• 
Concurrent use with sulfonylureas may cause hypoglycemia. Patient should treat 
hypoglycemia with oral glucose (dextrose), and not sucrose (cane sugar). This is because 
acarbose may delay the absorption time of sucrose. 
• 
This drug may cause abdominal pain, diarrhea, and flatulence. These side effects should 
subside in frequency and intensity with continued use. 
• 
Patient should take drug with the first bite of food at each main meal. 
• 
If dose is missed and meal completed, advise patient to skip dose and take at next meal. 
 
 
Generic Drug Name: ACETAZOLAMIDE 
Brand Name(s): Diamox ; Sequels  
Adverse Effects 
Serious: 
• 
Dermatologic: Stevens-Johnson syndrome (rare), Toxic epidermal necrolysis due to 
drug (rare) 
• 
Endocrine metabolic: Acidosis, Metabolic acidosis 
• 
Hematologic: Agranulocytosis, Aplastic anemia, Thrombocytopenia 
• 
Hepatic: Hepatic necrosis 
• 
Immunologic: Anaphylaxis 
• 
Ophthalmic: Angle-closure glaucoma 
• 
Other: Sulfonamide adverse reaction (rare) 
 
Common: 
• 
Adrenal gland failure 
• 
Chronic noncongestive angle-closure glaucoma 
• 
Cirrhosis 
• 
Hyponatremia/hypokalemia 
• 
Hyperchloremic acidosis 
• 
Hypersensitivity to acetazolamide 
• 
Severe hepatic or renal disease 
 
Patient Information 
• 
Instruct patient to avoid activities requiring mental alertness or physical coordination until 
drug effects are realized. 
• 
If used for prophylaxis of acute mountain sickness, advise patient a rapid ascent may still 
cause high-altitude pulmonary or cerebral edema. 
• 
If used for seizure control, advise patient against sudden discontinuation of drug. 
• 
This drug may cause weight loss, diarrhea, loss of appetite, nausea, altered sense of 
taste, vomiting, confusion, paresthesia, somnolence, depression, malaise, or metabolic 
acidosis. 
• 
This drug may also cause tinnitus early in therapy. 
• 
Instruct patient to report signs/symptoms of a sulfonamide adverse reaction. This would 
include severe skin reactions such as Stevens-Johnson syndrome (flu-like symptoms, 
spreading red rash, or skin/mucous membrane blistering), erythema multiforme (a less 
severe form of Stevens-Johnson), toxic epidermal necrolysis (widespread 
peeling/blistering of skin), and fulminant hepatic necrosis (symptoms of severe hepatic 
failure). 
• 
Advise diabetics that this drug may increase blood sugar level. 

 
 
 
 
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• 
Instruct patient to report polyuria if increased urination affects sleep. 
• 
Patient should avoid concomitant high-dose aspirin. 
 
Contraindications 
 
• 
adrenal gland failure 
• 
chronic noncongestive angle-closure glaucoma 
• 
cirrhosis 
• 
hyponatremia/hypokalemia 
• 
hyperchloremic acidosis 
• 
hypersensitivity to acetazolamide 
• 
severe hepatic or renal disease 
 
Precautions 
 
• 
adverse reactions common to sulfonamide derivatives may occur, including Stevens-
Johnson syndrome and toxic epidermal necrosis 
• 
concomitant high-dose aspirin 
• 
high dose may decrease diuresis 
• 
high dose may increase drowsiness and/or paresthesia 
• 
pulmonary obstruction or emphysema 
• 
rapid ascent may cause high-altitude pulmonary/cerebral edema 
 
 
 
Acetylsalicylic acid 
 
Common 
Serious  
Indigestion 
Nausea 
Vomiting 
 
Bleeding (3.9%, high-dose use) 
Tinnitus 
dyspepsia 
Bronchospasm 
Angioedema 
Reye’s syndrome 
 
Gastrointestinal ulcer (long term use) 
 
• 
Warn patients that due to risk of Reye's syndrome. Drug should never be used in children 
and teenagers with chickenpox or flu symptoms. 
• 
This drug may cause dyspepsia, nausea, vomiting, gastrointestinal ulcer, tinnitus, 
angioedema, or Reye's syndrome (persistent nausea/vomiting, somnolence, lethargy, 
confusion, combative behavior, decreased level of consciousness, seizure). 
• 
Instruct patient to report signs/symptoms of bleeding or gastrointestinal distress. 
• 
Patient should take drug with an 8-ounce glass of water. 
• 
Patient may take with food or milk. 
• 
Instruct patient to avoid alcohol during therapy. 
 

 
 
 
 
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Adalimumab 
 
Common 
Serious  
Hypertension (5%) 
Injection site pain (12-19%) 
Injection site reaction (8-20%) 
Rash (12%) 
Antibody development (1-12%) 
Positive antinuclear antibody (12%) 
Headache (12%) 
Sinusitis (11%) 
Upper respiratory infection (17%) 
 
Erythema multiforme 
Primary cutaneous vasculitis 
Stevens-Johnson syndrome 
Aplastic anemia (rare) 
Erythrocytosis (< 5%) 
Leukopenia (<5%) 
Pancytopenia (<5%) 
Thrombocytopenia (rare) 
Anaphylaxis (rare) 
Immune hypersensitivity reaction (1%) 
Malignant lymphoma (rare) 
Central nervous system demyelinating disease 
(rare) 
Multiple sclerosis (<5%) 
Paresthesia (<5%) 
Subdural hematoma (<5%) 
Interstitial lung disease 
Pulmonary fibrosis 
Tuberculosis (rare) 
Angioedema  
Cancer 
Infectious disease 
• 
Advise patient of increased risk of lymphoma and other malignancies. 
• 
Advise patient to avoid vaccines during therapy due to drug-induced immunosuppression. 
• 
Instruct patient to report a latex-sensitivity prior to administration, as needle cover of 
prefilled syringe contains dry natural rubber (latex derivative). 
• 
Drug may cause headache, rash, nausea, upper respiratory infection, and injection site 
reaction. 
• 
Instruct patient to report signs/symptoms of infection (including tuberculosis) or lupus-
like syndrome (arthralgias, myalgias, fatigue, skin rashes). 
• 
Advise patient to report signs/symptoms of heart failure (new onset or exacerbation of 
disease). 
• 
Tell patient to report signs/symptoms of hepatitis B during and after drug therapy. 
• 
Advise patient to report signs/symptoms of pancytopenia or cytopenia. 
• 
Advise patient to rotate injection sites. 
• 
Patient should avoid concomitant use of anakinra due to possible development of serious 
infections. 
Albendazole 
 
Adverse Effects 
Serious: 
• 
Dermatologic: Erythema multiforme, Stevens-Johnson syndrome 

 
 
 
 
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• 
Hematologic: Agranulocytosis (less than 1%), Aplastic anemia, Granulocytopenic 
disorder (less than 1%), Leukopenia (less than 1%), Pancytopenia (less than 1%), 
Thrombocytopenia (less than 1%) 
• 
Hepatic: Hepatotoxicity, With elevated liver enzymes 
• 
Renal: Acute renal failure (rare) 
• 
Neurologic: Seizures, Increased intracranial pressure, meningeal signs 
 
 
Common: 
• 
Gastrointestinal: Abdominal pain, Nausea, Vomiting 
• 
Neurologic: Headache 
 
Aldesleukin 
 
Risks and side effects related to Aldesleukin (IL-2) include those which are: 
 
Likely 
Less Likely 
Rare But Serious 
• 
Fever and chills 
including shaking chills 
• 
Flu like symptoms with 
headache, tiredness, 
aches and pains 
• 
Diarrhea 
• 
Loss of Appetite 
• 
A feeling of weakness 
and/or tiredness not 
relieved by sleep or rest 
• 
A mild drop in blood 
pressure 
• 
Skin rash including 
rash with the presence 
of macules (flat 
discolored areas) and 
papules (raised bumps) 
• 
Itching 
• 
Fluid retention and  
build-up in the tissues 
usually of the lower legs 
leading to an increase 
in weight 
• 
Increased levels of a 
chemical (creatinine) in 
the blood which could 
mean kidney damage 
• 
A temporary decrease 
in the amount of urine 
which could mean the 
kidneys are not 
working as well 
• 
Elevation in the blood 
• Nausea and vomiting 
• Low levels of certain salts in the body like 
sodium, calcium, magnesium and 
phosphate which may require treatment 
• High levels of uric acid in the blood which 
could damage the kidneys 
• Upset of the normal acid levels in your 
blood 
• Low levels of sugar in the body which may 
require that you take replacement 
• A condition (vascular or capillary leak 
syndrome) in which fluid and proteins 
leak out of tiny blood vessels and flow into 
surrounding tissues, resulting in 
dangerously low blood pressure which 
may lead to multiple organ failure such as 
kidney, heart or liver failure and shock. 
• Heart problems including an irregular or 
rapid heartbeat leading to unpleasant 
sensation in the chest 
• Dizziness 
• Cough 
• Stuffy or runny nose 
• Headache or head pain 
• Enlarged abdomen (belly)  
• Weight gain 
• Pain in the abdomen (belly) or other parts 
of the body 
• High blood sugar which may require 
treatment 
• Mood changes including depression, 
inability to sleep or excessive sleepiness, 
irritability and agitation, anxiety, 
• A severe allergic reaction that 
can be life-threatening and may 
lead to difficulty in breathing, a 
drop in blood pressure, and an 
irregular heart beat. 
• Heart attack or severe pain in 
the chest (angina) that can be 
life-threatening or fatal. 
• Abnormal electrical conduction 
within the heart which can 
cause irregular heartbeat and 
may be life threatening 
• Inflammation of the heart 
muscle which could lead to 
heart failure 
• A severe drop in blood pressure 
that will require treatment 
• A decrease in the factors in the 
blood that help your blood to 
clot normally 
• Bleeding which can occur in the 
head, stools, the nose, urine and 
other parts of the body 
• Convulsion or Seizures  
• Prolonged loss of consciousness 
(coma) 
• Inflammation of your colon 
(large bowel) which could lead 
to bloody diarrhea and may be 
life threatening or a hole may 
develop in the intestines which 
would cause leakage into the 
abdomen (belly) with pain and 

 
 
 
 
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of certain enzymes or 
bilirubin which could 
indicate liver irritation 
or damage  
• 
An increase in the 
blood of a type of white 
blood cell called an 
eosinophil. These are 
sometimes associated 
with allergic reactions 
• 
An increase in the 
number of white blood 
cells in the blood 
• 
Fewer red blood cells 
and platelets in the 
blood  
o a low number of red 
blood cells can make 
you feel tired and 
weak 
o a low number of 
platelets causes you 
to bruise and bleed 
more easily 
confusion, and mood swings such as 
feelings of suicide, feelings of 
aggressiveness 
• Noticeable changes in a person’s 
personality, behavior, and thinking 
• Trouble with memory 
• Aches and pains in the muscles and joints, 
sleep difficulties, a feeling of  
      extreme tiredness or not feeling well 
• Muscular discomfort or pain from 
infection or an unknown cause 
• Nerve damage that may cause pain, 
burning, numbness, and tingling 
• Inflammation and/or sores in the mouth 
that may make swallowing difficult and 
are painful (painful mouth sores) 
• Severe rashes which can result in loss of 
skin  
• Hair loss 
• Infections including those caused by 
bacteria, virus, and fungus which may 
require treatment 
• Blurred vision 
• A flushing of your skin with redness and a 
feeling of warmth   
• Widening of blood vessels 
• Fewer white cells  in the blood  
o a low number of white blood cells may 
make it easier to get infections  
• Decrease or increase in your thyroid 
hormones 
• Shortness of breath 
• Poor blood supply to the arms and legs 
infection 
• Inflammation of your pancreas 
which could cause pain in your 
abdomen and may be life-
threatening 
• Severe kidney damage (which 
may be permanent) 
• If you have ever been told that 
you have a disease such as 
lupus, rheumatoid arthritis or 
other disease that is caused by a 
disturbance in your immune 
system “autoimmune disease”,  
aldesleukin (IL-2) may cause 
these to be worse. 
• Damage to your lungs which 
could lead to fluid in the lungs 
and affect your ability to breath 
and the levels of oxygen in the 
blood  
• Stopping of breathing 
• Clotting of blood vessels which 
can lead to pain and swelling in 
the area of the clot. Such clots 
may break loose and cause 
damage or be life-threatening 
depending on where they go 
• Sudden death 
 
 

 
 
 
 
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Alprazolam 
 
Common 
Rare 
Hypotension (10%) 
Dermatitis (4%) 
Nausea (9-15%) 
Vomiting (9-15%) 
Diarrhea (9-15%) 
Constipation (9-15%) 
Increased salivation (4.2%) 
Increased appetite 
Weight change 
Coordination problem 
Dizziness 
Dysarthria 
Memory impairment 
Somnolence  
Depression 
Reduced libido 
tachycardia  
palpitations 
light sensitivity  
bullous 
taste alteration 
abnormal liver function test 
anaphylactic reaction 
• 
Patient should avoid activities requiring mental alertness or coordination until drug 
effects are realized. 
• 
This drug may cause increased appetite, changes in weight, constipation, dizziness, 
dysarthria, memory impairment, somnolence, depression, or reduced libido. 
• 
Advise patient and family to monitor for confusion with use, especially with elderly 
patients. 
• 
Advise patient against abrupt discontinuation of drug to prevent withdrawal symptoms. 
• 
Patient should avoid alcohol while taking drug. 
• 
Patient should not eat grapefruit or drink grapefruit juice while taking drug. 
 
Amantadine 
Adverse Effects 
Serious: 
• 
Cardiovascular: Cardiac arrest (rare), Cardiac dysrhythmia (rare), Congestive heart 
failure (0.1% to 1%), Hypotension (rare), Tachycardia (rare) 
• 
Dermatologic: Malignant melanoma 
• 
Hematologic: Agranulocytosis (Rare), Leukopenia (less than 0.1%), Neutropenia (less 
than 0.1%) 
• 
Immunologic: Immune hypersensitivity reaction 
• 
Neurologic: Neuroleptic malignant syndrome (rare) 
• 
Psychiatric: Suicidal intent (less than 0.1%) 
• 
Respiratory: Acute respiratory failure (rare), Pulmonary edema (rare) 
• 
Genitourinary: Urinary retention (0.1-1%) 
 
 

 
 
 
 
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Common: 
• 
Cardiovascular: Orthostatic hypotension (1% to 5%), Peripheral edema (1% to 5%) 
• 
Gastrointestinal: Constipation (1% to 5%), Diarrhea (1% to 5%), Loss of appetite (1% to 
5%), Nausea (5% to 10%), Xerostomia (1% to 5%) 
• 
Neurologic: Ataxia (1% to 5%), Confusion (1% to 5%), Dizziness (5% to 10%), 
Headache (1% to 5%), Insomnia (5% to 10%), Somnolence (1% to 5%) 
• 
Psychiatric: Agitation (1% to 5%), Anxiety (1% to 5%), Depression (1% to 5%), Dream 
disorder (1% to 5%), Feeling nervous (1% to 5%), Hallucinations (1% to 5%), Irritability 
(1% to 5%) 
• 
Other: Fatigue (1% to 5%) 
• 
 
Ambenonium Chloride   
 
Common 
Rare 
Sweating symptom 
Epigastric discomfort 
Excessive salivation 
Muscle cramp 
Muscle fasciculation 
Vertigo 
Blurred vision 
Excessive tear production 
Miosis 
Anxiety 
Urgent need to urinate 
Bronchorrhea 
Malaise 
Pulmonary edema 
Abdominal cramps 
Diarrhea 
Sialorrhea 
Nausea 
Vomiting 
Bradycardia  
• 
This drug may cause sweating, epigastric discomfort, excessive salivation, cramp, muscle 
fasciculation, vertigo, blurred vision, excessive tear production, miosis, anxiety, urgent 
desire to urinate, bronchorrhea, or malaise. 
• 
Patient should report signs/symptoms of a cholinergic crisis. 
• 
Advise patient there are multiple significant drug-drug interactions for this drug. Consult 
healthcare professional prior to new drug use (including over-the-counter and herbal 
drugs). 
• 
Instruct patient to call healthcare professional if a dose is missed, as drug should be given 
on a regular schedule. 
Amikacin 
 
Adverse Effects 
Serious: 
• 
Neurologic: Neuromuscular blockade finding, tremor, paresthesia, weakness,  
• 
Central Nervous System: Fever, headache, drowsiness, dizziness, ataxia, vertigo 
• 
Otic: Ototoxicity 

 
 
 
 
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• 
Renal: Nephrotoxicity 
• 
Respiratory: Respiratory tract paralysis 
 
Common: 
• 
None indicated 
 
Amiloride Hydrochloride 
 
Common 
Serious 
Orthostatic hypotension 
Hyperkalemia (10%) 
Diarrhea (3-8%) 
Loss of appetite (3-8%) 
Nausea (3-8%) 
Vomiting (3-8%) 
Headache (3-8%) 
Aplastic anemia 
Neutropenia (rare) 
• 
Instruct patient to rise slowly from a sitting/supine position, as drug may cause orthostatic 
hypotension. 
• 
This drug may cause diarrhea, loss of appetite, nausea, vomiting, or headache. 
• 
Instruct patient to immediately report signs/symptoms of hyperkalemia (paresthesia, 
muscular weakness, fatigue, flaccid paralysis of extremities). 
• 
Advise patient against sudden discontinuation of drug. 
• 
Patient should take tablet with food. 
• 
Patient should not drink alcohol while taking this drug. 
• 
Tell patient to avoid other potassium-conserving agents, such as spironolactone or 
triamterene, and potassium-containing supplements/salt substitutes while taking this drug. 
Aminocaproic acid 
Adverse Effects 
Serious: 
• 
Cardiovascular: Bradyarrhythmia, Hypotension, peripheral ischemia,  
• 
Dermatologic: Rash 
• 
Hematologic: Thrombosis, Agranulocytosis,Leukopenia 
• 
Musculoskeletal: Drug-induced myopathy, Rhabdomyolysis 
• 
Renal: Renal failure 
• 
Otic: Tinnitus, deafness 
• 
Respiratory: Nasal congestion, pulmonary embolism, dyspnea 
• 
Endocrine: Hyperkalemia 
 
Common: 
• 
Gastrointestinal: Nausea, Vomiting 
• 
Neurologic: Asthenia, Dizziness, Headache 
 

 
 
 
 
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Amitriptyline Hydrochloride   
 
Common 
Serious 
Weight gain 
Bloating symptom 
Constipation 
Xerostomia 
Asthenia 
Dizziness 
Headache  
Somnolence 
Blurred vision 
Fatigue 
Atrioventricular conduction pattern 
Cardiac dysrhythmia 
Hypertension 
Myocardial infarction (rare) 
Orthostatic hypotension 
Syncope 
Agranulocytosis (rare) 
Aplastic anemia (rare) 
Drug-induced eosinophilia (rare) 
Leucopenia (rare) 
Pancytopenia 
Purpuric disorder (rare) 
Thrombocytopenis (rare) 
Decreased liver function (rare) 
Jaundice (rare) 
Cerebrovascular accident (rare) 
Seizure (rare) 
Worsening depression (rare) 
Suicidal thoughts (rare) 
Suicide (rare) 
• 
Instruct patient to report use of a MAO inhibitor within 14 days prior to initiating drug 
therapy. 
• 
Patient should avoid activities requiring mental alertness or coordination until drug 
effects are realized. 
• 
This drug may cause anticholinergic symptoms, weight gain, bloating, fatigue, orthostatic 
hypotension, or syncope. 
• 
Instruct patient to report worsening depression, suicidal ideation, or unusual changes in 
behavior, especially at initiation of therapy or with dose changes. Children and 
adolescents are at higher risk for these effects during the first few months of therapy. 
• 
Advise patient that symptomatic improvement may not be seen for a few weeks. 
• 
Warn patient against sudden discontinuation of drug. 
• 
Patient should not drink alcohol while taking this drug. 
 
 
Amoxapine 
 
Adverse Effects 
Serious: 
• 
Cardiovascular: Heart block, Myocardial infarction, Prolonged QT interval 
• 
Hematologic: Agranulocytosis (less than 1%) 
• 
Neurologic: Neuroleptic malignant syndrome (less than 1%), Seizure (less than 1%), 
Tardive dyskinesia 
• 
Psychiatric: Depression, Worsening, Suicidal thoughts, Suicide 

 
 
 
 
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Common 
• 
Central Nervous System: Drowsiness (14%) 
• 
Gastrointestinal: Constipation (12%), Xerostomia (14%) 
• 
Neurologic: Somnolence (14%) 
• 
Ophthalmic: Blurred vision (7%) 
• 
Dermatologic: Edema, Skin Rash 
• 
Other: Fatigue (14%) 
 
Amoxicillin 
 
Serious: 
• 
Dermatologic: Stevens-Johnson syndrome, Toxic epidermal necrolysis 
• 
Gastrointestinal: Hemorrhagic colitis 
• 
Immunologic: Anaphylaxis 
 
Common 
• 
Gastrointestinal: Diarrhea (frequent) 
 
 
AMPICILLIN 
Brand Name(s): Amcill  ;  Omnipen  ;  Penbritin  ;  Pfizerpen-A  ;  Polycillin  ;  Rosampline  ;  
Totacillin 
Adverse Effects 
Serious: 
• 
Dermatologic: Erythema multiforme, Erythroderma, Stevens-Johnson syndrome, Toxic 
epidermal necrolysis 
• 
Gastrointestinal: Pseudomembranous enterocolitis 
• 
Hematologic: Agranulocytosis, Thrombocytopenia 
• 
Immunologic: Anaphylaxis, Hypersensitivity reaction 
 
Common 
• 
Dermatologic: Rash, Urticaria 
• 
Gastrointestinal: Diarrhea 
 
Patient Information 
• 
Drug may decrease effectiveness of oral contraceptives with concurrent use. 
Recommend additional form of birth control. 
• 
This drug may cause diarrhea, nausea, vomiting, or rash. 
• 
Advise patient to report the development of a late skin rash with symptoms of fever, 
fatigue, and sore throat. 
• 
Patient should take 1/2 h before or 2 h after meals. 
 
Contraindications 

 
 
 
 
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• 
hypersensitivity to ampicillin products/penicillins 
 
Precautions 
 
• 
hypersensitivity to cephalosporins 
• 
patients with mononucleosis; increased risk for rash 
 
 
Anakinra 
Common 
Serious 
Injection site reaction (71%) 
Cardiorespiratory arrest 
Bacterial cellulitis 
Malignant melanoma 
Neutropenia (0.4%) 
Infectious disease (2-3%) 
Malignant lymphoma 
Bacterial musculoskeletal infection 
Bacterial pneumonia 
Breast cancer 
cancer 
• 
Advise patient to avoid live vaccines during therapy due to drug-induced 
immunosuppression. 
• 
Instruct patient to report a rubber or latex sensitivity prior to administration, as needle 
cover of prefilled syringe contains latex. 
• 
Instruct patient to report signs/symptoms of infection. 
• 
Advise patient to rotate injection sites. 
 
 
Anastrozole 
 
Common 
Serious 
Hypertension (2-13%) 
Peripheral edema (5-10%) 
Vasodilatation (25-36%) 
Rash (6-11%) 
Nausea (11-20%) 
Vomiting (8-11%) 
Increased liver test (1-10%) 
Lymphedema (10%) 
Arthralgia (2-15%) 
Arthritis (17%) 
Backache (10-12%) 
Bone pain (6-12%) 
Osteoporosis (11%) 
Asthenia (13-19%) 
Chest pain (5-7%) 
Ischemic heart disease (adjuvant therapy, 
4%) 
Myocardial infarction (adjuvant therapy, 
1.2%) 
Thrombophlebitis (adjuvant therapy, 2-5%) 
Hypercholesterolemia (9%) 
Anemia (2-5%) 
Deep venous thrombosis (2%) 
Leukopenia (2-5%) 
Thromboembolic disorder (2-4%) 
Hepatitis (0.01-1%) 
Immune hypersensitivity reaction (0.01%) 
Bone fracture (2-10%) 

 
 
 
 
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Headache (9-18%) 
Insomnia (2-10%) 
Depression (2-13%) 
Mood change (19%) 
Menopausal flushing (11-36%) 
Dyspnea (8-11%) 
Increasing frequency of cough 97-1150 
Pharyngitis (6-14%) 
Fatigue (11-17%) 
Pain (11-17%) 
Cerebral ischemia (2%) 
breast cancer (6%) 
Malignant neoplasm of endometrium of 
corpus uteri (0.2%) 
Vaginal bleeding (1-5%) 
Cancer (5%) 
Tumor flare (3%) 
 
• 
This drug may cause peripheral edema, vasodilation, nausea, arthralgia, arthritis, back or 
bone pain, asthenia, headache, depression, dyspnea, cough, or pharyngitis. 
• 
Instruct patient to report signs/symptoms of bone loss, including osteopenia, 
osteoporosis, and bone fracture.  
• 
Instruct patient to report signs/symptoms of anemia, thrombophlebitis, or profuse vaginal 
bleeding. 
Ascorbic acid 
 
Adverse Effects 
Serious: 
• 
None indicated 
 
Common: 
• 
Dermatologic: Injection site reaction, Pain and swelling 
• 
Gastrointestinal: Diarrhea, Large doses 
• 
Hematologic: Iron overload, Large doses 
• 
Renal: Nephrolithiasis, Large doses 
 
Atorvastatin 
 
Common 
Rare ≤3% 
Adominal pain (3.8%) 
Diarrhea (5.3%) 
Headache (2.5% to 16.7%) 
Rash (1.1% to 3.9%) 
Arthralgia (up to 5.1%) 
Myalgia (up to 5.6%) 
Asthenia (3.8%) 
Sinusitis (2.8% to 6.4%) 
Infection (2.8% to 10.3%) 
Rhabdomyolysis (rare) 
Rupture of Tendon 
Alopecia  
Thrombocytopenia (<0.1%) 
Short term memory loss (rare) 
Constipation (2.5%) 
Flatulence (1.15 to 2.8%) 
Indigestion (1.3% to 2.8%) 
Increased liver enzymes, mild (0.2% to 2.3%) 
Immune hypersensitivity reaction (up to 2.8%) 
Backache (2.8%) 
Dizziness (2% or more) 
Insomnia (2% or more) 
Arthritis (2% or more) 

 
 
 
 
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Nausea (2% or more) 
Chest pain (2% or more) 
Swelling of arm and legs (2% or more) 
Albuminuria (2% or more) 
Hematuria (2% or more) 
Urinary tract infection (2% or more) 
Bronchitis(2% or more) 
Pharyngitis (2.5%) 
Rhinitis (2% or more) 
Flu-like illness (2.5%) 
 
This drug may cause headaches. 
 
Instruct patient to report signs/symptoms of rhabdomyolysis (myalgias, dark urine, arthralgias, 
fatigue). 
 
Patient should not drink alcohol while taking drug. 
 
Patient should not eat grapefruit or drink grapefruit juice while taking drug. 
 
Atovaquone 
 
Adverse Effects 
Serious:  
• 
Dermatologic: Erythema multiforme, Stevens-Johnson syndrome 
• 
Hematologic: Methemoglobinemia 
• 
Hepatic: Liver failure 
 
Common: 
• 
Dermatologic: Rash (6.3% to 46%) 
• 
Gastrointestinal: Abdominal pain (4% to 21%), Diarrhea (3.2% to 42%), Nausea (4.1% 
to 32%), Vomiting (2.2% to 22%) 
• 
Neurologic: Asthenia (8% to 31%), Headache (16% to 31%), Insomnia (10% to 19%) 
• 
Respiratory: Cough (14% to 25%), Dyspnea (15% to 21%), Rhinitis (5% to 24%) 
• 
Hematologic: Anemia (4-6%), Neutropenia (3-5%) 
• 
Other: Fever (0.6% to 40%), Infectious disease (18% to 22%) 
 
Azacitidine 
 
Adverse Effects 
Serious:  
• 
Cardiovascular: Atrial fibrillation (less than 5%), Cardiorespiratory arrest (less than 5%), 
Congestive cardiomyopathy (less than 5%), Heart failure (less than 5%) 
• 
Dermatologic: Cellulitis (less than 5%) 
• 
Hematologic: Anemia, Grade 3 and 4 (13.7%), Febrile neutropenia (13.7% to 16.4%), 
Neutropenia, Grade 3 and 4 (61.1%), Pancytopenia (less than 5%), Sepsis, Associated 
with neutropenia (less than 5%), Thrombocytopenia, Grade 3 and 4 (58.3%) 

 
 
 
 
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• 
Immunologic: Septic shock (less than 5%) 
• 
Neurologic: Cerebral hemorrhage (less than 5%), Coma, Intracranial hemorrhage (less 
than 5%), Seizure (less than 5%) 
• 
Renal: Renal failure, Renal tubular acidosis 
• 
Respiratory: Interstitial lung disease, Respiratory distress (less than 5%) 
 
Common: 
• 
Cardiovascular: Chest pain (16.4%), Pallor (16%), Pitting edema (15%), Peripheral 
edema (7-19%) 
• 
Central nervous system: Fever (30% to 52%), fatigue (13% to 36%), headache (22%), 
dizziness (19%), anxiety (5% to 13%), depression (12%), insomnia (9% to 11%), malaise 
(11%), pain (11%) 
• 
Endocrine & metabolic: Hypokalemia (6% to 13%) 
• 
Dermatologic: Erythema (7.4% to 16.8%), Erythema at injection site (35% to 42.9%), 
Induration of skin (less than 5%), Injection site bruising (5.1% to 14.1%), Injection site 
pain (18.9% to 22.7%), Injection site reaction (13.6% to 29.1%), Petechiae (11.4% to 
23.6%), Pruritic rash (less than 5%), Pruritus (6.8% to 12%) 
• 
Gastrointestinal: Constipation, Diarrhea, Loss of appetite, Nausea, Vomiting 
• 
Hematologic: Anemia, Any grade (51.4% to 69.5%), Ecchymosis (30.5%), Leukopenia 
(18.3% to 48.2%), Neutropenia, Any grade (32.3% to 65.7%), Thrombocytopenia, Any 
grade (65.5% to 69.7%) 
• 
Musculoskeletal: Arthralgia 
• 
Neurologic: Dizziness (18.6%), Headache (21.8%), Insomnia (8.6% to 10.9%), Lethargy 
(7.4% to 7.7%) 
• 
Respiratory: Dyspnea (14.9% to 29.1%), Nasopharyngitis (14.5%), Pneumonia (10.9%), 
Upper respiratory infection (9.1% to 12.7%) 
• 
Other: Fatigue (24%), Fever (30.3% to 51.8%), Lymphadenopathy (10%), herpes 
simplex (9%), night sweats (9%), transfusion reaction (7%), mouth hemorrhage (5%) 
 
Azathioprine 
 
Common 
Serious 
Gastritis medicamentosa 
Nausea (12%) 
Vomiting (12%) 
Rash (infrequent) 
Diarrhea (infrequent) 
Pancreatitis (2-12%) 
Leukopenia (5-16%) 
Megaloblastic anemia 
Thrombocytopenia 
Hepatotoxicity (3-10%) 
Cancer (rare) 
Infection (20% in renal transplant patients) 
Immune hypersensitivity reaction (<0.1%) 
 
This drug may cause myelosuppression and gastrointestinal toxicity.  
 
Instruct patient to report any unusual bleeding or bruising.  
 
Instruct patient to report signs/symptoms of infection.  
 
Patient may take drug with food or in divided doses to decrease gastrointestinal intolerance.  

 
 
 
 
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 
Advise patient there are multiple significant drug-drug interactions for this drug. Consult 
healthcare professional prior to new drug use (including over-the-counter and herbal drugs).  
 
Aztreonam 
 
Adverse Effects 
Serious:  
• 
Dermatologic: Erythema multiforme (adults, less than 1%), Toxic epidermal necrolysis 
(adults, less than 1%) 
• 
Gastrointestinal: Diarrhea, GI bleeding, nausea, pseudomembranous colitis, vomiting 
• 
Hematologic: Neutropenia (up to 3.2%), Pancytopenia (adults, less than 1%), 
Thrombocytopenia (adults, less than 1%) 
• 
Immunologic: Anaphylaxis (adults, less than 1%) 
• 
Otic: Ototoxicity 
• 
Renal: Nephrotoxicity 
• 
Other: Angioedema (adults, less than 1%) 
 
Common: 
• 
Cardiovascular: Chest discomfort (inhalation solution, 8%) 
• 
Gastrointestinal: Abdominal pain (inhalation solution, 7%), Vomiting (inhalation solution, 
6%) 
• 
Hepatic: Alkaline phosphatase raised, ALT/SGPT level raised (6.5%), AST/SGOT level 
raised (3.8%) 
• 
Renal: Serum creatinine raised (pediatrics, 5.8%) 
• 
Respiratory: Cough (inhalation solution, 54%), Nasal congestion (inhalation solution, 
16%), Pain in throat (inhalation solution, 12%), Wheezing (inhalation solution, 16%) 
• 
Other: Fever (up to 1%) 
 
 
Baclofen 
 
Adverse Effects 
Serious:  
• 
Neurologic: Aseptic meningitis, with intrathecal administration, Coma, Seizure 
• 
Other: Death, Abrupt withdrawal 
Common: 
• 
Gastrointestinal: Constipation (; oral: 2% to 6%), Nausea (4% to 12%) 
• 
Neurologic: Asthenia (5% to 15%), Dizziness (5% to 15%), Somnolence (10% to 63%) 
• 
Other: Fatigue (2% to 4%), Hypotension (0-9%), Vision changes 
 
 

 
 
 
 
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Balsalazide 
 
Common 
Serious 
Abdominal pain (6%) 
Diarrhea (5%) 
Nausea (5%) 
Headache (8%) 
Vomiting (4%) 
Arthralgia (4%) 
Respiratory tract infection (4%) 
Abnormal electrolytes 
Colitis 
Exacerbation  
Pancreatitis 
hepatotoxicity 
 
BCNU 
 
 
Common 
Happens to 21-100 children 
out of every 100 
Occasional 
Happens to 5-20 children 
out of every 100 
Rare 
Happens to <5 children out 
of every 100 
Immediate: 
Within 1-2 days 
of receiving drug 
Burning feeling in the vein 
while drug is being given, 
nausea, vomiting 
Inflammation and/or 
blockage of a vein at the 
injection site (L), sudden 
redness of the face 
Burning feeling in the chest 
while the medication is being 
given by vein, brown 
discoloration where the 
medication comes in contact 
with the skin 
Prompt: 
Within 2-3 
weeks, prior to 
next course 
Decrease in the number of red 
and white blood cells and 
platelets made in the bone 
marrow(L), hair loss (L) 
Abnormal function of the 
liver (L) 
Abnormal function of the 
kidneys (L) 
Delayed: 
Any time later 
during therapy, 
excluding the 
above conditions 
Abnormal lung function (L) 
 
Damage/scarring of lung 
tissue (L) 
Late: 
Any time after 
completion of 
treatment 
 
 
A new cancer or leukemia 
resulting from this treatment. 
 (L) Toxicity may also occur later. 
 
 
Betamethasone 
 
Adverse Effects 
Serious:  
• 
Endocrine metabolic: Cushing's syndrome, Hyperglycemia, Primary adrenocortical 
insufficiency 
• 
Musculoskeletal: Osteoporosis 
• 
Ophthalmic: Cataract, Glaucoma 
• 
Respiratory: Pulmonary tuberculosis 
 

 
 
 
 
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Common: 
• 
Cardiovascular: Hypertension 
• 
Dermatologic: Atrophic condition of skin, Finding of skin healing Skin infections (16-
43%)Endocrine metabolic: Decreased body growth 
• 
Gastrointestinal: Disorder of gastrointestinal tract 
• 
Immunologic: At risk for infection 
• 
Psychiatric: Depression, Euphoria 
 
Bevacizumab 
 
The following table outlines the side effects of bevacizumab that we know about. The side effects 
presented may not be dose-dependent, which means that a higher dose of bevacizumab many not 
result in more severe side effects.  More importantly, it means that a lower dose may not mean 
fewer side effects and that serious side effects may occur even at the lowest doses tested. 
 
Common 
Happens to 21-100 
patients out of every 100 
Occasional 
Happens to 5-20 patients 
out of every 100 
Rare 
Happens to <5 patients out of 
every 100 
Immediate:  
Within 1-2 days 
of receiving 
drug 
High blood pressure, 
low blood pressure, 
fever, chills, shaking 
chills, headache, nausea, 
vomiting 
Difficulty breathing, 
cough or voice change 
Allergic Reaction 
Prompt or 
delayed: Within 
2-3 weeks or 
any time after, 
during 
treatment 
High blood pressure, 
Excess amount of 
protein in the urine, 
nosebleeds 
 
Mouth sores, sore throat, 
vomiting blood, blood in 
sputum or spit, rash, 
peeling of the skin, 
hives, blood clot in vein 
or artery 
Kidney damage, liver function test 
elevations 
Late:  
Anytime after 
completion of 
treatment. 
 
 
 
Unknown 
Timing and 
Frequency 
 
Infection, joint pains, 
chest pains, low blood 
counts*, fatigue, weight 
loss, loss of appetite, 
change in bowel habits. 
Clots in the arteries,**Severe 
bleeding in  the tumor, lungs,  or 
in the brain, intestinal leakage*, 
slow wound healing, heart strain*, 
fluid around the heart or in the 
lungs*, collection of air in the 
chest that causes part or all of a 
lung to collapse *, Abnormal heart 
rhythm*, Clotting abnormalities,* 
mental status changes*, seizure*, 
fainting spells,* tingling in the 
hands and feet*, visual changes* 
and frequent urination* 
* There have been reported cases but the relationship to the study drug is unclear. 
**The use of bevacizumab is associated with an increased risk of conditions related to clots in the 
arteries, including stroke or heart attack; these conditions can be life-threatening or fatal.  When 
several studies were looked at together, problems due to clots in arteries were increased up to 4-

 
 
 
 
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5% in patients receiving chemotherapy plus bevacizumab compared to chemotherapy alone (2%).  
Patients who were elderly and with past history of clots in the arteries appeared to be at a greater 
risk for these problems. 
 
There is currently no experience using bevacizumab in children.  Studies of the drug in animals 
showed a decrease in ovarian function and abnormal bone growth.  These side effects appeared to 
be at least partially reversible, but have not been assessed in cases of long-term use of the drug.  
The greatest effects on growth were on the long leg bones of growing animals.  Adult women of 
child-bearing age who have received bevacizumab have continued to have normal periods.  The 
potential risks for impaired growth and development are of particular concern to children.   
 
 
In studies in adults, many patients experience mild to moderate increases in blood pressure which 
may need to be lowered with medication.  Uncontrolled high blood pressure can be serious or 
life-threatening. Some patients have also experienced excessive amounts of protein in the urine 
which has rarely progressed to permanent and serious kidney disease. Because this drug acts on 
blood vessels bleeding and blood clots appear to be more common than with other therapies.  
Minor bleeding episodes including nosebleeds are not uncommon.  However, bleeding has 
occurred in the brain, the stomach and intestines and within the tumor itself, occasionally causing 
it to rupture.   Blot clots are most often associated with intravenous catheters, but can also involve 
the brain  (stroke), the lungs (pulmonary embolus) and the blood supply to other vital organs of 
the body.   In adults these side effects, while infrequent, have been life-threatening and even fatal. 
We will closely monitor children on this study for all of these effects. 
 
Patients who develop anemia or low platelet counts may require red blood cell or platelet 
transfusions and as a result transfusion of blood and/or blood components may be necessary. 
Transfusions may be accompanied or followed by fever and/or reactions that can cause kidney 
failure, heart failure, anemia, hepatitis, A.I.D.S. (acquired immune deficiency syndrome) and 
other infections. 
 
If a person gets pregnant while receiving bevacizumab, it could be dangerous for the baby. You 
should not become pregnant or father a baby while on this study. You should not nurse (breast 
feed) a baby while on this study. Ask about counseling and more information about preventing 
pregnancy. 
 
We will tell you if we learn any new information that may affect your health, welfare, or decision 
to stay in this study.  
 
 
BIOTIN 
Brand Name(s): Appearex 
Adverse Effects 
• 
gastrointestinal upset 
• 
administration of anticonvulsant medications may impair Biotin absorption 
 
Patient Information 
• 
None indicated 
 
Contraindications 
• 
hypersensitivity to Biotin 
 
 
2/22/05

 
 
 
 
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Precautions 
• 
None indicated 
 
 
 
 
 
 
 
 
BISACODYL 
Brand Name(s): Alophen Pills ;  Bisac-Evac 
Adverse Effects 
Serious:  
• 
Gastrointestinal: Atony of colon 
 
Common: 
• 
Gastrointestinal: Abdominal colic, Abdominal discomfort, Diarrhea, Proctitis, With 
suppository use 
 
Patient Information 
• 
This drug may cause diarrhea or abdominal pain, discomfort, and cramping. The 
suppositories may cause proctitis. 
• 
Patient should expect to have a bowel movement within 15 to 60 min after suppository 
administration. 
• 
Instruct patient to report rectal bleeding or failure to have bowel movements within 12 h 
after taking oral formulation. 
• 
Patient should not take bisacodyl tablets within 1 h of antacids, milk, or milk products. 
• 
Patient should not take bisacodyl for more than 7 days, unless approved by healthcare 
professional. 
 
Contraindications 
• 
appendicitis 
• 
intestinal obstruction 
• 
gastroenteritis 
 
Precautions 
• 
abdominal pain, nausea, vomiting 
• 
rectal bleeding or failure to have bowel movements after administration 
• 
inflammatory bowel disease 
• 
sudden, persistent change in bowel habits 
• 
ulcerated hemorrhoids of rectal fissures 
• 
use for more than 7 days is not recommended 
 
 
 
 
 
 
 

 
 
 
 
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Bortezomib 
 
Risks and side effects related to the bortezomib include those which are: 
 
Likely 
• 
Decrease in a red blood cell protein that carries oxygen in the body 
• 
Decreased number of blood cells that help to clot the blood 
• 
Fatigue 
• 
Fever 
• 
Loss of appetite 
• 
Constipation 
• 
Diarrhea 
• 
Nausea 
• 
Vomiting 
• 
Infection 
• 
Swelling of the arms and legs 
• 
Nerve damage causing numbness, tingling, burning 
 
 Less Likely   
• 
Decreased total number of white blood cell 
• 
Decreased number of a type of white blood cell 
• 
Low blood pressure 
• 
Difficulty sleeping or falling asleep 
• 
Chills, shivering 
• 
Rash/flaking or shedding of outer layer of skin 
• 
Dehydration 
• 
Heartburn 
• 
Abnormally slow bowel contraction 
• 
Irritation or sores in the lining of the throat 
• 
Bleeding of the digestive tract 
• 
Nosebleed 
• 
Fever with dangerously low white blood cell count 
• 
Blood infection 
• 
Pneumonia 
• 
Infection which occurs due to a decreased number of a type of white blood cell 
• 
Muscle weakness of the whole body 
• 
Dizziness 
• 
Anxiety 
• 
Weakness or paralysis caused by damage to nerves 
• 
Fainting 
• 
Blurred vision 
• 
Belly pain 
• 
Back pain 
• 
Bone pain 
• 
Leg pain 
• 
Head pain 
• 
Joint pain 
• 
Muscle pain 
• 
Nerve pain 

 
 
 
 
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• 
Cough 
• 
Shortness of breath 
• 
Excess fluid that accumulates in the pleural cavity, the fluid-filled space that surrounds 
the lungs 
 
Rare but serious 
• 
A hole in the digestive tract 
• 
Syndrome associated with high blood pressure characterized by headache, confusion, 
seizures, and vision loss associated with imaging findings 
• 
Kidney failure 
 
Bromocriptine 
 
Serious:  
• 
Cardiovascular: Coronary artery thrombosis, Postpartum, Heart valve disorder, 
Myocardial infarction, Postpartum (rare), Pericardial effusion 
• 
Gastrointestinal: Gastrointestinal ulcer 
• 
Neurologic: Cerebrovascular accident (rare), Seizure (rare) 
• 
Psychiatric: Delusions, Hallucinations, Psychotic disorder 
• 
Respiratory: Pleural effusion, Pulmonary fibrosis, Thickening of pleura 
 
Common: 
• 
Cardiovascular: Hypotension (type 2 diabetes, 2.2%) 
• 
Endocrine: Hypoglycemia (type 2 diabetes 3.7-8.6%);  
• 
Gastrointestinal: Constipation (acromegaly, 14%; hyperprolactinemic indications, 3%; 
type 2 diabetes, 5.8% to 11.3%), Diarrhea (hyperprolactinemic indications, 3%; type 2 
diabetes, 8.1% to 8.8%), Indigestion (acromegaly, 4%; type 2 diabetes, 7.5%), Nausea 
(acromegaly, 18%; hyperprolactinemic indications, 49%; type 2 diabetes, 25.4% to 
32.5%), Vomiting (acromegaly, 2%; hyperprolactinemic indications, 5%; type 2 diabetes, 
5.3% to 8.1%) 
• 
Neurologic: Asthenia (type 2 diabetes, 12.5% to 18.9%), Dizziness (hyperprolactinemic 
indications, 17%; type 2 diabetes, 11.9% to 14.8%), Headache (hyperprolactinemic 
indications, 19%; type 2 diabetes, 11.4% to 16.8%), Somnolence ( 3% to 6.6%) 
• 
Ophthalmic: Amblyopia (type 2 diabetes, 5.3% to 7.5%) 
• 
Respiratory: Rhinitis (type 2 diabetes 10.7% to 13.8%), Sinusitis (type 2 diabetes, 7.4% 
to 10%) 
• 
Other: Fatigue (hyperprolactinemia indications, 7%; type 2 diabetes, 13.9%) 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Brompheniramine 
Serious:  
• 
None indicated 
 
Common: 
• 
Gastrointestinal: Xerostomia 
• 
Neurologic: Somnolence 
• 
Respiratory: Thick sputum, Bronchial 
 
 
Budesonide 
 
Serious:  
• 
Cardiovascular: Syncope (inhalation, 1% to 3%); Chest Pain (0-3%), Palpitations (0-
5%), Tachyarrythmia (0-5%) 
• 
Endocrine metabolic: Cushing's syndrome, Secondary hypocortisolism 
• 
Immunologic: Cow's milk protein sensitivity, Immune hypersensitivity reaction (rare) 
• 
Ophthalmic: Cataract (rare), Glaucoma (rare) 
 
Common: 
• 
Dermatologic: Contact dermatitis (0.75-4%), Eczema (0-3%), Rash (0-4%) 
• 
Gastrointestinal: Diarrhea (inhalation, 4%; oral, 10%), Nausea (inhalation, 1.8% to 6%; 
oral, 11%) 
• 
Musculoskeletal: Arthralgia (inhalation, 6%; oral, 5%) 
• 
Neurologic: Headache (inhalation, 3%; oral, 21%) 
• 
Respiratory: Epistaxis (intranasal, 8%; inhalation, 2% to 4%), Nasal stinging/burning 
(intranasal, greater than 1%), Respiratory tract infection (inhalation, 3% to 38%; oral, 
11%), Sinusitis (inhalation, 3% to 16%; oral, 8%) 
 
 
Bumetanide 
 
Common 
Serious 
Hypotension (0.8%) 
Hyperuricemia (18.4%) 
Hypokalemia (14.7%) 
Nausea (0.6%) 
Dizziness (1.1%) 
Headache (0.6%) 
Thrombocytopenia (0.2%) 
 
Instruct patient to report signs/symptoms hypokalemia, dehydration, or persistent fluid 
retention. 
 
Patient may take drug with food to minimize gastric irritation. 
 
Patient should not drink alcohol while taking this drug. 

 
 
 
 
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Bupropion 
 
Known side effects of Bupropion:  
 
Bupropion may cause side effects. Tell your doctor if any of these symptoms are severe 
or do not go away:  
• 
drowsiness 
• 
excitement 
• 
dry mouth 
• 
dizziness 
• 
headache 
• 
nausea 
• 
vomiting 
• 
uncontrollable shaking of a part of the body 
• 
weight loss 
• 
constipation 
• 
excessive sweating 
Some side effects can be serious. If you experience any of the following symptoms or 
those listed in the IMPORTANT WARNING section, call your doctor immediately:  
• 
seizures 
• 
confusion 
• 
hallucinating (seeing things or hearing voices that do not exist) 
• 
irrational fears 
• 
fever 
• 
rash or blisters 
• 
itching 
• 
hives 
• 
swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs 
• 
hoarseness 
• 
difficulty breathing or swallowing 
• 
chest pain 
• 
muscle or joint pain 
• 
rapid, pounding, or irregular heartbeat 
 
Buspirone 
Serious:  
• 
Cardiovascular: Congestive heart failure (rare), Myocardial infarction (rare) 
• 
Neurologic: Cerebrovascular accident (rare) 
 
Common: 
• 
Gastrointestinal: Nausea (3%) 

 
 
 
 
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• 
Neurologic: Asthenia (2%), Confusion (2%), Dizziness (9%), Excitement (2%), 
Headache (3%), Numbness (2%) 
• 
Ophthalmic: Blurred vision (2%) 
• 
Psychiatric: Feeling angry (2%), Feeling nervous (4%), Hostile behavior (2%) 
 
 
Calcitriol 
Adverse Effects 
Serious:  
• 
Dermatologic: Dermatitis, Acute blistering 
• 
Endocrine metabolic: Poisoning by vitamin D, Hypercalcemia syndrome 
 
Common: 
• 
Endocrine metabolic: Hypercalcemia 
 
 
 
Captopril 
 
Adverse Effects 
Serious:  
• 
Dermatologic: Stevens-Johnson syndrome 
• 
Gastrointestinal: Intestinal angioedema 
• 
Hematologic: Agranulocytosis (0.1% to 0.2%), Neutropenia (0.1% to 0.2%) 
• 
Immunologic: Anaphylactoid reaction 
• 
Neurologic: Seizures 
• 
Other: Angioedema (0.1%) 
 
Common: 
• 
Cardiovascular: Hypotension 
• 
Dermatologic: Rash (4-7%), Pruritis (2%),  
• 
Endocrine metabolic: Hyperkalemia (11%) 
• 
Gastrointestinal: Disorder of taste(2-4%), Diarrhea (0.5-2%), Nausea (0.5-2%)  
• 
Respiratory: Cough (0.5% to 2%) 
 
 
 
 
 
 
 
 

 
 
 
 
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Carbamazepine 
 
Common 
Serious 
Hypertension  
Hypotension 
Lightheadedness 
Nausea (frequent) 
Vomiting (frequent) 
Clumsiness 
Confusion 
Dizziness 
Nystagmus 
Somnolence 
Blurred vision 
Diplopia  
 
Atrioventricular block 
Cardiac dysrhythmia 
Congestive heart failure 
Syncope 
Stevens-Johnson syndrome 
Toxic epidermal necrolysis 
Hypocalcemia 
Hyponatremia (4% to 21.7%) 
Acute intermittent porphyria 
Garanulocytosis 
Aplastic anemia 
Bone marrow depression 
Drug-induced eosinophilia  
Leukocytosis 
Leukopenia 
Pancytopenia 
Thrombocytopenia 
Hepatitis 
Acute renal failure 
Nephrotoxicity 
angioedema 
 
Instruct patient to report use of an MAO inhibitor within 14 days prior to initiation of drug 
therapy. 
 
This drug may decrease effectiveness of oral contraceptives with concurrent use. Recommend 
additional form of birth control. 
 
Patient should avoid activities requiring mental alertness or coordination until drug effects are 
realized. 
 
Drug may cause dizziness, drowsiness, unsteadiness, nausea, or vomiting. 
 
Advise patient to report signs/symptoms of serious dermatologic reactions, such as Stevens-
Johnson syndrome (flu-like symptoms, spreading red rash, or skin/mucous membrane 
blistering) or toxic epidermal necrolysis (widespread peeling/blistering of skin). 
 
Instruct patient to report signs/symptoms of myelosuppression or hepatic toxicity. 
 
Advise patients to report signs/symptoms of psychosis, confusion, or agitation. 
 
Patient should take drug with food. 
 
Advise patient against sudden discontinuation of drug. 
 
Patient should not take the drug suspension with other liquid medicinal agents or diluents, as 
precipitation may occur. 
 
Patient should not eat grapefruit or drink grapefruit juice while taking this drug. 
 
Carbidopa/LEVOdopa 
 
Common 
Serious 
Loss of appetite 
Nausea 
Vomiting 
Heart disease 
Othostatic hypotension (1%) 
Dyskinesia (frequent) 
Psychotic disorder 

 
 
 
 
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 
This drug may cause loss of appetite, nausea, or vomiting. 
 
Instruct patient to report signs/symptoms of gastrointestinal bleeding and dyskinesia. 
 
Advise diabetic patients to monitor for and report difficulties with glycemic control. 
 
Patients with history of asthma or severe pulmonary disease should report an exacerbation of 
symptoms. 
 
Drug may increase risk of suicidal behavior. Tell patient to report exacerbation of underlying 
depression or psychosis. 
 
Advise patient against sudden discontinuation of drug. 
 
Patients using concomitant antihypertensives may be at increased risk for postural hypotension. 
 
Advise patient that use of MAO inhibitors concurrently or within 2 wks of levodopa/carbidopa 
is contraindicated. 
 
Instruct patient using regular tablets to take a missed dose as soon as possible, but if next dose 
is in less than 2 h, skip the missed dose. 
 
 
Carbinoxamine 
 
Adverse Effects 
Serious:  
• 
None indicated 
 
Common: 
• 
Dermatologic: Contact dermatitis 
• 
Gastrointestinal: Xerostomia, Anorexia, Diarrhea, Nausea, Vomiting 
• 
Neurologic: Dizziness, Headache, Sedated, Somnolence 
• 
Respiratory: Nasal mucosa dry 
 
 
Carboplatin 
Risks and side effects related to carboplatin include those which are: 
 
Likely 
Less Likely 
Rare but serious 
• 
Nausea and vomiting  
• 
Fewer red blood cells and 
white blood cells and 
platelets in the blood  
o a low number of red 
blood cells can make 
you feel tired and weak 
o a low number of white 
blood cells can make it 
easier to get infections 
o a low number of 
platelets causes you to 
bruise and bleed more 
easily 
• Allergic reactions (can be 
severe and life-threatening 
causing difficulty in breathing 
and or a drop in blood 
pressure) 
• Rash 
• Metallic taste 
• Numbness and tingling in the 
fingers and toes 
• Hair loss 
• Constipation or diarrhea 
• Pain in your abdomen 
• Temporary changes in vision 
• Damage to the ear causing 
• Damage to the liver   
• Damage to the kidney  
• Leukemia later in life 
 

 
 
 
 
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• 
Abnormal levels of certain 
salts in the body like sodium 
and potassium 
• 
 
hearing and balance problems 
• A feeling of weakness and/or 
tiredness 
• Inflammation and/or sores in 
the mouth (and/or throat and 
/or esophagus, the tube that 
leads from the mouth to the 
stomach) that may make 
swallowing difficult and are 
painful (painful mouth sores) 
 
 
CCNU (lomustine) 
 
Possible side effects of lomustine: 
 
Common 
Occasional 
Rare 
Immediate: Within 1-2 
days of receiving drug. 
Nausea, vomiting 
 
Diarrhea, hair loss, confusion, loss 
of muscle coordination, sleepiness, 
mouth sores, blindness caused by 
lack of function in an area of the 
brain responsible for vision 
Prompt: 
Within 
2-3 
weeks of receiving the 
drug. 
Low number of red and 
white 
blood 
cells 
and 
platelets in the blood. This 
often results in weakness, 
increased risk of infection 
and increased bleeding. 
Loss 
of 
appetite 
High level of liver enzymes in the 
blood 
Delayed: Anytime later 
during therapy excluding 
the above conditions. 
 
 
Lung damage, kidney damage, low 
number of white blood cells and 
platelets 
Late: 
Anytime 
after 
completion of treatment. 
 
 
Continued decrease in the number 
of white blood cells and platelets 
made in the bone marrow, which 
may become more of a problem 
after repeated doses. 
 
 
Cefaclor 
 
Adverse Effects 
Serious:  
• 
Dermatologic: Stevens-Johnson syndrome, Toxic epidermal necrolysis 
• 
Gastrointestinal: Pseudomembranous enterocolitis 
• 
Hematologic: Hemolytic anemia 
• 
Other: Serum sickness due to drug (0.024% to 0.5%) 
 
Common: 
• 
Gastrointestinal: Diarrhea (1.4%) 

 
 
 
 
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Cefadroxil 
 
Adverse Effects 
Serious:  
• 
Dermatologic: Erythema multiforme, Stevens-Johnson syndrome 
• 
Gastrointestinal: Clostridium difficile diarrhea 
• 
Hematologic: Thrombocytopenia 
• 
Hepatic: Liver failure 
• 
Immunologic: Anaphylaxis, Hypersensitivity reaction 
 
Common: 
• 
None indicated 
 
 
Cefazolin 
 
Adverse Effects 
Serious:  
• 
Dermatologic: Stevens-Johnson syndrome 
• 
Gastrointestinal: Clostridium difficile colitis, Pseudomembranous enterocolitis 
• 
Hematologic: LeukopeniaImmunologic: Anaphylaxis, Immune hypersensitivity reaction 
• 
Neurologic: Encephalopathy, Seizure 
• 
Renal: Renal failure 
 
Common: 
• 
Dermatologic: Pruritus 
• 
Gastrointestinal: Diarrhea 
• 
Hematologic: Drug-induced eosinophilia 
 
 
 
 
Cefepime 
 
Adverse Effects 
Serious:  
• 
Dermatologic: Stevens-Johnson syndrome, Toxic epidermal necrolysis 
• 
Gastrointestinal: Pseudomembranous enterocolitis 
• 
Immunologic: Anaphylaxis 
• 
Neurologic: Encephalopathy, Myoclonus, Seizure 

 
 
 
 
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Common: 
• 
Dermatologic: Rash (1.1% to 4%) , Pruritis (0.1-1%) 
• 
Endocrine metabolic: Hypophosphatemia (2.8%) 
• 
Gastrointestinal: Diarrhea (0.1% to 3%) 
• 
Hematologic: Direct Coombs test positive (16.2%) 
• 
Hepatic: ALT/SGPT level raised (2.8%), AST/SGOT level raised (2.4%) 
 
 
Cefotaxime 
 
Adverse Effects 
Serious:  
• 
Cardiovascular: Cardiac dysrhythmia 
• 
Dermatologic: Erythema multiforme, Stevens-Johnson syndrome, Toxic epidermal 
necrolysis 
• 
Hematologic: Agranulocytosis/Leukopenia/Thrombocytopenia (less than 1%), 
Granulocytopenic disorder 
• 
Immunologic: Hypersensitivity reaction (2.4%) 
 
Common: 
• 
Dermatologic: Injection site reactions,, Rash (2.2%),  
• 
Gastrointestinal: Diarrhea, Vomiting, Nausea 
 
 
 
Cefotetan 
 
Adverse Effects 
Serious:  
• 
Dermatologic: Stevens-Johnson syndrome, Toxic epidermal necrolysis, Erythema 
multiforme 
• 
Gastrointestinal: Pseudomembranous enterocolitis 
• 
Hematologic: Hemolytic anemia, Blood coagulation disorder (3.2%), Leukopenia (2%), 
Thrombocytopenia (3.5%) 
• 
Immunologic: Anaphylaxis 
• 
Neurologic: Seizure 
 
Common: 
• 
Dermatologic: Rash (0.6-1.5%) 
• 
Gastrointestinal: Diarrhea (0.6% to 1.25%), Nausea (0.14% to 1.25%) 

 
 
 
 
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Cefoxitin 
 
Adverse Effects 
Serious:  
• 
Dermatologic: Erythema multiforme, Stevens-Johnson syndrome 
• 
Gastrointestinal: Pseudomembranous enterocolitis 
• 
Immunologic: Anaphylaxis 
• 
Neurologic: Seizure 
Common: 
• 
Dermatologic: Injection site reaction 
• 
Hematologic: Thrombophlebitis 
 
 
Ceftazidime 
Adverse Effects 
Serious:  
• 
Dermatologic: Stevens-Johnson syndrome, Toxic epidermal necrolysis, Erythema 
multiforme 
• 
Gastrointestinal: Pseudomembranous enterocolitis 
• 
Hematologic: Increased prothrombin time (0.5%),  
• 
Immunologic: Anaphylaxis 
• 
Neurologic: Asterixis, Coma, Encephalopathy, Myoclonia, Seizure 
 
Common: 
• 
Gastrointestinal: Diarrhea 
 
Cefuroxime 
Adverse Effects 
Serious:  
• 
Dermatologic: Erythema multiforme (rare), Stevens-Johnson syndrome (rare), Toxic 
epidermal necrolysis (rare) 
• 
Hematologic: Thrombocytopenia (rare) 
• 
Immunologic: Anaphylaxis (rare), Hypersensitivity reaction 
• 
Renal: Interstitial nephritis (rare) 
 
Common: 
• 
Hematologic: Eosinophilia (14-32%),  

 
 
 
 
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Celecoxib Toxicity: 
 
 
Common 
Happens to 21-100 
children out of 
every 100 
Occasional 
Happens to 5-20 
children out of every 
100 
Rare 
Happens to < 5 children out of every 100 
Immediate: 
Within 1-2 days of 
receiving drug 
May mask fever in 
neutropenic 
patients (L) 
Dyspepsia, diarrhea 
Anaphylaxis (especially with history of 
sulfa or aspirin hypersensitivity, or asthma 
triad: asthma with nasal polyps, and 
urticaria), angioedema, flatulence, nausea, 
headache, dizziness, rashes (including 
Stevens-Johnson syndrome, erythema 
multiforme) 
Prompt: 
Within 2-3 weeks, 
prior to the next 
course 
 
Upper respiratory tract 
infection 
Fluid retention (L),  peripheral edema, GI 
bleed, or bleeding from peptic ulcer disease 
(L), sinusitis, pharyngitis, rhinitis  
Delayed: 
Any time later 
during therapy, 
excluding the 
above conditions 
 
 
 
Mild elevation of 
SGOT (AST)/SGPT 
(ALT) 
Severe hepatic reactions (jaundice, fatal 
fulminant hepatitis, liver necrosis, hepatic 
failure), decreased renal function, renal 
papillary necrosis, anemia, cardiovascular 
and thromboembolic complications 
(aggravated hypertension, coronary 
artery disorder, myocardial infarction, 
pulmonary embolism, deep venous 
thrombosis, unstable angina, transient 
ischemic attacks, ischemic cerebrovascular 
accidents) 
Unknown 
Frequency and 
Timing: 
 
Administration of celecoxib to animals early in pregnancy caused an increased incidence of 
ventricular septal defects, a rare event, and fetal alterations, such as ribs fused, sternebrae 
fused, sternebrae misshapen and diaphragmatic hernias.  Celecoxib is excreted in the milk 
of lactating rats at concentrations similar to those in plasma. Limited data from one subject 
indicate that celecoxib is also excreted in human milk 
(L) Toxicity may also occur later. 
 
 
 
Cetirizine 
Adverse Effects 
Serious:  
• 
None indicated 
 
Common: 
• 
Gastrointestinal: Xerostomia 
• 
Neurologic: Headache, Somnolence (13.7%), Asthenia (5.2%) 
• 
Other: Fatigue (5.9%) 
 

 
 
 
 
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CETUXIMAB 
Brand Name(s): Erbitux 
Adverse Effects 
Serious:  
• 
Cardiovascular: Cardiorespiratory arrest (squamous cell carcinoma of the head and 
neck, 2% to 3%), Myocardial infarction, Shock, Sudden cardiac death (squamous cell 
carcinoma of the head and neck, 2% to 3%) 
• 
Dermatologic: Abscess, Acneiform eruption, Grades 3 and 4 (1% to 17%), Radiation 
dermatitis, Grades 3 and 4 (squamous cell carcinoma of the head and neck (with 
radiation), 23%) 
• 
Endocrine metabolic: Hypomagnesemia, Grades 3 and 4 (5% to 17%) 
• 
Hematologic: Leukopenia, Grades 3 and 4 (colorectal cancer (with irinotecan), 17%) 
• 
Immunologic: Immune hypersensitivity reaction, Infection due to Staphylococcus 
aureus, Sepsis (1% to 4%) 
• 
Neurologic: Loss of consciousness 
• 
Renal: Renal failure (colorectal cancer, 1%) 
• 
Respiratory: Interstitial lung disease (less than 0.5%), Pulmonary embolism 
• 
Other: Complication of infusion, Grades 3 and 4 (2% to 5%) 
 
Common: 
• 
Dermatologic: Acneiform eruption, Any grade (70% to 88%), Application site reaction 
(squamous cell carcinoma of the head and neck (with radiation), 18%), Dry skin 
(squamous cell carcinoma of the head and neck (with platinum plus 5-FU), 14%; 
colorectal cancer (monotherapy), 49%), Nail changes (colorectal cancer (monotherapy), 
21%), Pruritus (squamous cell carcinoma of the head and neck (with radiation), 16%; 
colorectal cancer (monotherapy), 40%), Radiation dermatitis, Any grade (squamous cell 
carcinoma of the head and neck (with radiation), 86%), Rash (87% to 89%; squamous 
cell carcinoma of the head and neck (with platinum plus 5-FU), 28%) 
• 
Endocrine metabolic: Dehydration (squamous cell carcinoma of the head and neck 
(with radiation), 25%), Hypomagnesemia, Any grade (55%; squamous cell carcinoma of 
the head and neck (with platinum plus 5-FU), 11%), Weight loss (squamous cell 
carcinoma of the head and neck (with radiation), 84%) 
• 
Gastrointestinal: Abdominal pain (colorectal cancer (monotherapy), 59%), Constipation 
(colorectal cancer (monotherapy), 46%), Diarrhea (19% to 39%; colorectal cancer (with 
irinotecan), 72%), Loss of appetite (squamous cell carcinoma of the head and neck (with 
platinum plus 5-FU), 25%), Nausea (49% to 55%), Stomatitis (colorectal cancer 
(monotherapy), 25%), Vomiting (29% to 37%) 
• 
Immunologic: Infectious disease (35% to 44%; squamous cell carcinoma of the head 
and neck (with radiation), 13%) 
• 
Neurologic: Asthenia, Any grade (56% to 73%), Confusion (colorectal cancer, 15%), 
Headache (19% to 33%), Insomnia (colorectal cancer (monotherapy), 30%) 
• 
Psychiatric: Anxiety (colorectal cancer (monotherapy), 14%), Depression (colorectal 
cancer (monotherapy), 13%) 
• 
Respiratory: Cough (colorectal cancer (monotherapy), 29%), Dyspnea (colorectal 
cancer (monotherapy), 48%), Pharyngitis (squamous cell carcinoma of the head and 
neck (with radiation), 26%) 
 
 
Patient Information 

 
 
 
 
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• 
Drug causes sun-sensitivity and can exacerbate any skin reactions which may occur. 
Advise patient to wear sunscreen and hats and to avoid tanning beds. 
• 
This drug may cause hypomagnesemia, weight loss, abdominal pain, constipation, 
diarrhea, gastrointestinal mucositis, nausea, anemia, asthenia, headache, insomnia, 
depression, cough, dyspnea, pain, or fever. 
• 
Advise patient, especially those receiving concomitant radiation therapy, to report 
signs/symptoms of dermatologic toxicity. This may be characterized as a severe 
acneform rash (acne, rash, maculopapular rash, pustular rash, dry skin, exfoliative 
dermatitis). 
• 
Instruct patient to report signs/symptoms of acute or worsening pulmonary symptoms, as 
this may indicate pulmonary toxicity. 
• 
Advise patients with preexisting cardiac disease to report acute or worsening cardiac 
symptoms. 
 
Contraindications 
• 
specific contraindications have not been determined  
 
Precautions 
• 
cardiopulmonary arrest and/or sudden death have been reported in patients with 
squamous cell carcinoma of the head and neck treated with concomitant radiation 
therapy or platinum-based therapy with 5-fluorouracil; patients with a history of 
arrhythmias, congestive heart failure, or coronary artery disease may be at increased 
risk; monitoring of serum electrolytes recommended  
• 
infusion reactions, some serious (eg, bronchospasm, stridor, hypotension, shock, loss of 
consciousness, myocardial infarction, cardiac arrest) and fatal, have been reported; 
immediately and permanently discontinue for serious infusion reactions  
• 
concomitant use with radiation therapy and cisplatin (unapproved use); death and serious 
cardiotoxicity have been reported in patients with squamous cell carcinoma of the head 
and neck  
• 
dermatologic toxicities, including acneform rash, hypertrichosis, and infectious sequelae 
(eg, Staphylococcus aureus sepsis, abscess formation, cellulitis) have been reported; 
monitoring and dosage modifications recommended for severe acneform rash  
• 
electrolyte abnormalities (eg, hypomagnesemia, hypocalcemia, hypokalemia) have 
occurred; monitoring recommended  
• 
interstitial lung disease (ILD) has been reported; permanently discontinue for confirmed 
ILD  
• 
sun exposure; limit exposure for up to 2 months following the last cetuximab dose  
• 
report suspected adverse reactions to the FDA at 1-800-FDA-1088 or 
www.fda.gov/medwatch  
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Chlorambucil 
 
Adverse Effects 
Serious:  
• 
Dermatologic: Erythema multiforme (rare), Skin reaction - finding, Stevens-Johnson 
syndrome (rare), Toxic epidermal necrolysis (rare) 
• 
Hematologic: Acute leukemia, Leukopenia, Myelosuppression, Neutropenia, 
Pancytopenia 
• 
Hepatic: Hepatotoxicity 
• 
Immunologic: Drug fever, Immune hypersensitivity reaction 
• 
Neurologic: Peripheral neuropathy, Seizure 
• 
Psychiatric: Hallucinations 
• 
Reproductive: Infertility, Reversible or permanent 
• 
Respiratory: Pneumonitis, acute 
• 
Other: Secondary malignant neoplastic disease 
 
Common: 
• 
Hematologic: Anemia, Thrombocytopenia 
 
Chlorothiazide 
 
Common 
Serious 
Hypotension 
Alopecia 
Light sensitivity 
Phototoxicity 
Rash 
Urticaria 
Hyperglycemia 
Hyperuricemia 
Constipation 
Diarrhea 
Loss of appetite 
Nausea 
Vomiting 
Spasticity 
Dizziness 
Headache 
Blurred vision 
Xanthopsia 
Impotence 
Scaling eczema (rare) 
Stevens-Johnson syndrome (rare) 
Toxic epidermal necrolysis (rare) 
Abnormal electrolytes 
Disorder of hematopoietic structure (rare) 
Hepatotoxicity (rare) 
Systemic lupus erythematosus (rare) 
      
 
Patient should avoid activities requiring coordination until drug effects are realized, as this drug 
may cause dizziness or spasticity. 

 
 
 
 
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 
This drug may cause alopecia, hyperglycemia, constipation, diarrhea, loss of appetite, nausea, 
vomiting, headache, blurred vision, xanthopsia, or impotence. 
 
Instruct patient to report symptomatic hypotension. 
 
Patient should not drink alcohol while taking this drug. 
 
Avoid concomitant use of lithium. 
 
chlorproMAZINE  
 
 
Common 
Serious 
Hypotension 
Orthostatic hypotension 
Diminished sweating  
Light sensitivity 
Constipation 
Xerostomia 
Akathisia 
Dizziness 
Drug-induced tardive dystonia 
Dystonia 
Extrapyrmidal disease 
Parkinsonian  
Somnolence 
Tardive dyskinesia 
Blurred vision 
Epithelial keratopathy 
Eye/vision changes 
Retinitis pigmentosa 
Nasal congestion 
Prolonged QT interval (rare) 
Torsades de pointes (rare) 
Obstipation (rare) 
Paralytic ileus (rare) 
Agranulocytosis (rare) 
Hematopoietic structure disorder (rare) 
Leucopenia (rare) 
Thrombocytopenia (rare) 
Cholestatic jaundice syndrome (rare) 
Neuroleptic malignant syndrome (rare) 
Seizure (rare) 
Priapism (rare) 
Death 
      
 
Patient should avoid activities requiring mental alertness, coordination, or visual acuity until 
drug effects are realized. 
 
Drug can cause sun-sensitivity. Advise patient to use sunscreen and avoid tanning beds. 
 
Drug may impair heat regulation. Advise patient to use caution with activities leading to an 
increased core temperature, such as strenuous exercise, exposure to extreme heat, or 
dehydration. 
 
Advise patient to report any visual disturbances. Patients receiving moderate to high-dose 
therapy for long periods of time may need to have periodic eye exams. 
 
This drug may cause anticholinergic effects, hypotension, diminished sweating, akathisia, or 
somnolence. 
 
Instruct patient to report signs/symptoms of agranulocytosis (eg, sudden appearance of sore 
throat or other signs of infection), especially between the fourth and tenth weeks of therapy. 
 
Advise patient to report signs/symptoms of neuromuscular adverse effects such as parkinsonian 
extrapyramidal disease, tardive dyskinesia (jerky muscle movements, tongue thrusting, facial 
grimacing/ticks, random movements of extremities), or neuroleptic malignant syndrome 
(sweating, fever, stupor, unstable blood pressure, muscular rigidity, autonomic dysfunction). 
 
Patients on concurrent antipsychotic therapy should report signs/symptoms of encephalopathic 
syndrome (weakness, lethargy, fever, tremulousness, confusion). 
 
Advise patient against sudden discontinuation of drug. 

 
 
 
 
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 
Patient should not drink alcohol or use other CNS depressants while taking this drug. 
 
Patient should avoid exposure to organophosphorus insecticides during drug therapy. 
 
chlorproPAMIDE 
 
Common 
Serious 
Cutaneous hypersensitivity 
Hypoglycemia 
Nausea 
Vomiting 
Hematopoietic structure disorder 
Hypoglycemia (severe) 
 
This drug may cause cutaneous hypersensitivity, nausea, or vomiting. 
 
Advise diabetic patients to monitor for signs/symptoms hypoglycemia and to report difficulties 
with glycemic control. Elderly or debilitated patients may be at increased risk for severe 
hypoglycemia. 
 
Patient should take drug with breakfast. 
 
Patient should avoid alcohol while taking this drug. 
 
Chlorzoxazone 
 
Adverse Effects 
Serious:  
• 
Gastrointestinal: Gastrointestinal hemorrhage (rare) 
• 
Hepatic: Hepatotoxicity (rare) 
• 
Immunologic: Anaphylaxis (rare) 
 
Common: 
• 
Cardiovascular: Lightheadedness 
• 
Neurologic: Dizziness, Excitement, Paradoxical, Somnolence 
• 
Other: Malaise 
 
 
 
Ciclosporin 
 
Common 
Serious 
Hirsutism 
Pruritus 
Diarrhea 
Nausea 
Vomiting 
Headache (2% to 25%) 
Seizure (1% to 25%) 
Tremor (3% to 55%) 
Burning sensation in eye (with ophthalmic 
Hypertension (frequent) 
Hyperkalemia (rare) 
Hypomagnesemia 
Gingival enlargement 
Pancreatitis (rare) 
Hepatotoxicity 
Anaphylaxis (with IV use, rare) 
Post-transplant lymphoproliferative disorder (rare) 
Paresthesia (1-11%) 

 
 
 
 
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emulsion, 17%) 
Conjunctival hyperemia 
Eye discharge 
Excessive tear production  
Pain in eye (with ophthalmic emulsion, 1-5%) 
Visual disturbance (with ophthalmic emulsion, 1-
5%) 
Hemolytic uremic syndrome (rare) 
Nephrotoxicity (frequent) 
Infection 
      
 
Patient should not use ophthalmic preparation in an infected eye. 
 
Advise patient to avoid vaccines during therapy unless approved by a healthcare professional. 
 
To decrease the risk of skin malignancies, advise patient to avoid excessive exposure to 
ultraviolet light. 
 
Drug may cause hypertension, renal dysfunction, hirsutism, diarrhea, nausea, vomiting, 
headache, tremor, or gingival enlargement. 
 
The ophthalmic preparation may cause a foreign body or burning sensation in the eye. 
 
Instruct patient to report signs/symptoms of transplant rejection or infection. 
 
Advise patient to report signs/symptoms of hepatotoxicity or encephalopathy, especially 
patients receiving high-dose therapy. 
 
Instruct patients to report signs/symptoms of nephrotoxicity, especially when on concomitant 
nephrotoxic drugs. 
 
Patients using the ophthalmic preparation should report visual disturbances, conjunctival 
hyperemia, eye pain, or discharge from eye. 
 
Patient should allow at least 5 minutes between instillation of this drug and other ophthalmic 
products. 
 
Warn patient that rinsing the oral solution syringe with water either before or after use will 
cause a variation in dose and should be avoided. 
 
Tell patient to remove contact lenses prior to instilling ophthalmic formulation. Lenses may be 
reinserted 15 minutes following instillation. 
 
Patient should not eat grapefruit or drink grapefruit juice while taking this drug. 
 
Patient should avoid concomitant potassium-sparing drugs, potassium supplements, and 
foods/salt substitutes that are high in potassium. 
 
Tell patient that there are multiple significant drug-drug interactions for this drug. Consult 
healthcare professional prior to new drug use (including over-the-counter and herbal drugs). 
 
Ciprofloxacin 
 
Serious:  
• 
Cardiovascular: Cardiorespiratory arrest (less than 1%), Myocardial infarction (less than 
1%), Prolonged QT interval, Syncope (less than 1%), Torsades de pointes 
• 
Dermatologic: Stevens-Johnson syndrome, Toxic epidermal necrolysis 
• 
Gastrointestinal: Clostridium difficile infection, Gastrointestinal hemorrhage (less than 
1%), Pancreatitis (less than 1%), Pseudomembranous enterocolitis (less than 1%) 
• 
Hematologic: Agranulocytosis, Aplastic anemia, Bone marrow depression, Hemolytic 
anemia, Leukopenia, Pancytopenia, ThrombocytopeniaHepatic: Elevated liver function 
tests, Hepatotoxicity,  
• 
Immunologic: Immune hypersensitivity reaction, Serious (rare) 

 
 
 
 
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• 
Musculoskeletal: Myasthenia gravis, Exacerbation, Rupture of tendon, Tendinitis, 
Arthropathy 
• 
Neurologic: Raised intracranial pressure, Seizure (less than 1%) 
• 
Psychiatric: Depression (less than 1%), Psychotic disorder (less than 1%) 
• 
Renal: Acute renal failure (less than 1%), Hemorrhagic cystitis (less than 1%) 
 
Common: 
• 
Dermatologic: Rash (up to 1.8%), Pruritis (2-3%) 
• 
Gastrointestinal: Diarrhea (1.6% to 4.8%), Nausea (2.5% to 2.7%), Vomiting (1% to 
4.8%) 
• 
Musculoskeletal: Arthralgia (9.3-13.7%), Myalgia (9.3%) 
• 
Neurologic: Headache (2% to 3.9% .) 
• 
Ophthalmic: Burning sensation in eye, Pain in eye 
 
 
 
Cisplatin 
There is a risk of very uncommon or previously unknown side effects occurring.  Treatment may 
result in allergic reactions, the decreased ability of the body to fight infection, and abnormalities in 
growth or structure of the fetus.  Very rarely, one or a combination of these side effects may cause 
death.  These drugs may interact with other drugs to produce unexpected side-effects. 
 
Cisplatin  
 
Common 
Happens to 21-100 children out of 100 
Occasional 
Happens to 5-20 
children out of every 
100 
Rare 
Happens to <5 
children out of every 
100 
Immediate: 
Within 1-2 days of 
receiving drug 
Nausea (L), vomiting (L) 
Metallic Taste (L) 
Allergic reaction  
Prompt: 
Within 2-3 weeks, 
prior to the next course 
Loss of appetite (L), low level of 
magnesium salts in the blood (L), 
hearing loss (high sounds [L]), damage to 
kidney tissue (L), Decrease in the 
number of red and white blood cells and 
platelets made in the bone marrow 
Abnormal levels of 
certain salts in the body 
like sodium and 
potassium (L) 
Numbness, tingling, 
clumsiness (L), 
ringing in the ears 
(L), seizure (L), 
damage to the liver 
(L) 
Delayed: 
Any time later during 
therapy, excluding the 
above conditions 
 
 
Hearing Loss 
Late: 
Any time after 
completion of 
treatment 
 
 
Cancer caused by 
treatment for a previous 
cancer or leukemia 
(L) Toxicity may also occur later. 
 
 
 

 
 
 
 
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Citalopram 
Adverse Effects 
Serious:  
• 
Cardiovascular: Myocardial infarction (0.1% to 1%), Prolonged QT interval (0.5% to 
1.9%), Torsades de pointes, Tachycardia (0.5-1%) 
• 
Neurologic: Cerebrovascular accident (0.1% to 1%) 
• 
Psychiatric: Depression, worsening (rare), Suicidal thoughts, Suicide 
• 
Other: Serotonin syndrome 
 
Common: 
• 
Dermatologic: Diaphoresis (5% to 18%) 
• 
Gastrointestinal: Constipation (13%), Diarrhea (8%), Nausea (20% to 21%), Vomiting 
(4% to 20%), Xerostomia (17% to 20%) 
• 
Musculoskeletal: Arthralgia (2%), Myalgia (2%) 
• 
Neurologic: Dizziness (up to 14%), Headache (up to 18%), Insomnia (15%), Sedated 
(15%), Somnolence (18%), Tremor (8% to 16%) 
• 
Psychiatric: Agitation (3% to 10%) 
• 
Reproductive: Disorder of ejaculation (6.1%) 
Respiratory: Rhinitis (5%), Sinusitis (3%), Upper Respiratory Tract Infection (5%)Other: Fatigue 
(5%);  
 
 
Clemastine 
Adverse Effects 
Serious:  
• 
None indicated 
 
Common: 
• 
Gastrointestinal: Xerostomia 
• 
Neurologic: Sedated, Somnolence 
• 
Renal: Urinary retention 
 
Clindamycin 
Adverse Effects 
Serious:  
• 
Dermatologic: Erythema multiforme 
• 
Gastrointestinal: Pseudomembranous enterocolitis 
• 
Hematologic: Agranulocytosis 
• 
Hepatic: Increased liver function test, Jaundice 
 

 
 
 
 
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Common: 
• 
Dermatologic: Dry skin, Rash 
• 
Gastrointestinal: Abdominal pain, Diarrhea, Nausea 
• 
Reproductive: Candida vaginitis (14% vaginal cream ; 1.5% vaginal suppository), 
Vaginal pain (up to 2% vaginal suppository) 
 
Clofarabine 
 
Risks and side effects related to the clofarabine include: 
Likely 
Less Likely 
Rare but serious 
• 
A fast heartbeat which may 
cause pain in the chest 
• 
A feeling of extreme tiredness 
not relieved by sleep 
• 
A decrease in blood pressure  
• 
Pain in the abdomen (belly) 
• 
Diarrhea 
• 
Nausea and/or vomiting 
• 
Headache 
• 
Fever  
• 
Chills 
• 
Anxiety 
• 
Fever with a low white blood 
cell count which could mean 
that you have an infection and 
might require hospitalization 
and treatment with antibiotics 
• 
Loss of appetite 
• 
Elevation in the blood of 
certain enzymes found in the 
liver and bilirubin (a substance 
that comes from the liver 
breaking down waste products) 
which may mean the liver is 
not working as well as normal 
• 
Skin rash  
• 
Skin rash with inflammation 
• 
Itching 
• 
Red spots on the skin from low 
platelets 
• 
Bloody nose 
• 
Fewer white blood cells, red 
blood cells and platelets in the 
blood (may be prolonged) 
o a low number of white 
blood cells can make it 
easier to get infections 
o a low number of red blood 
cells can make you feel 
• 
The rapid death of large 
numbers of tumor cells which 
can cause the potassium and 
phosphate salts and the uric 
acid in the blood to rise quickly 
and this could lead to a life-
threatening irregular heart beat 
or damage to the kidneys. 
• 
Fluid build-up in the tissues 
• 
Sleepiness and weakness 
• 
Changes to your emotions such 
that you feel depressed, 
anxious, agitated, irritable or 
confused 
• 
Difficulty sleeping or falling 
asleep 
• 
High blood pressure 
• 
Cough or shortness of breath 
• 
Reddening of the face with 
feelings of warmth when the 
drug is infusing 
• 
A fast rate of respiration that 
may cause pain in the chest 
• 
A change in alertness, 
concentration, and memory 
• 
Allergic reaction 
• 
Constipation  
• 
Dizziness 
• 
Tremor (shakiness usually of 
the hands) 
• 
Shaking chills 
• 
Fainting  
• 
Low levels of oxygen in the 
blood which may make you feel 
short of breath  
• 
Inflammation and/or sores in 
the mouth that may make 
swallowing difficult and are 
painful (painful mouth sores) 
• 
Severe loss of water from the 
body (dehydration) which if 
untreated may cause low 
blood pressure and severe 
loss of salts such as sodium 
and potassium from the body 
and could lead to the kidneys 
failing which could be life-
threatening 
• 
Capillary leak syndrome: a 
condition in which fluid and 
proteins leak out of tiny blood 
vessels and flow into 
surrounding tissues, resulting 
in dangerously low blood 
pressure. Capillary leak 
syndrome may lead to 
multiple organ failure such as 
kidney, heart or liver failure 
and shock. 
• 
Inflammation of the pancreas 
(an organ in the abdomen 
which produces insulin and 
certain digestive chemicals) 
which may affect the function 
of the pancreas and which 
may cause pain in the 
abdomen (belly) which can be 
severe and may increase the 
blood sugar 
• 
Severe inflammation and 
damage to the large intestine 
wall which can be life 
threatening 
• 
Inflammation or damage to 
the liver which can be severe 
and life-threatening and 
which may lead to an 
enlarged liver and spleen, 
bleeding from the veins in the 

 
 
 
 
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tired and weak 
o a low number of platelets 
causes you to bruise and 
bleed more easily 
• 
Abnormal levels of potassium 
or magnesium in the body 
which may require that you 
take extra potassium by mouth 
or vein 
• 
An increase in an enzyme 
(called lipase) that helps break 
down fats in the body 
• 
Pain including back, bone, arm, 
or leg pain 
• 
The skin and the whites of the 
eyes appears yellow as a result 
of too much bilirubin (a 
substance that comes from the 
liver breaking down waste 
products) in the blood 
• 
Weight loss 
• 
Aches and pains in the muscles 
and joints 
• 
Bleeding from the bladder, gut, 
mouth, or gums 
• 
Vomiting or coughing blood 
• 
Fluid build-up in the lungs that 
can make you feel short of 
breath 
• 
A life threatening condition in 
which the level of oxygen in the 
blood becomes too low or the 
level of carbon dioxide in the 
blood becomes too high 
• 
Damage to the sac around the 
heart which can lead a build-up 
of fluid around the heart which 
may be painful and affect the 
ability of the heart to work 
normally but in most cases is 
only mild and temporary 
• 
Severe rash with redness and 
pain on the palms of the hand 
and soles of the feet 
• 
Bruising of the skin from low 
platelets 
• 
Rash with redness or red bumpy 
rash  
• 
Increased levels of a chemical 
(creatinine) in the blood which 
could mean kidney damage 
• 
Occasional sudden sharp pain 
in the rectal area 
• 
Infections including those 
caused by bacteria, virus, and 
fungus and can be found in the 
lung, the blood, the skin and 
other places in the body  
• 
A life-threatening form of 
severe blood infection that 
usually results from the 
presence of bacteria and their 
toxins in the bloodstream and is 
esophagus (the passage that 
leads from the throat to the 
stomach), a yellow 
appearance to the skin and 
fluid collection in the 
abdomen which makes it look 
larger 
• 
Abnormal clotting of the 
blood that can lead to 
formation of blood clots 
and/or bleeding with 
abnormal findings on 
neurologic exam 
• 
Severe kidney damage (which 
may be permanent) 
• 
Severe rashes which can 
result in loss of skin and 
damage to mucous 
membranes and which may 
be life-threatening (occurred 
in combination of other drugs 
known to cause this effect) 
• 
Failure of the bone marrow to 
produce blood cells and 
platelets which can be life 
threatening.  
• 
A change to the heart such 
that it does not pump the 
blood as well which may 
make you tired, weak, feel 
short of breath, and retain 
fluid 
 

 
 
 
 
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characterized especially by 
persistent hypotension with 
reduced blood flow to organs 
and tissues and often organ 
dysfunction 
• 
Abnormal high level of 
potassium in the blood which 
may cause irregular heart beat 
and require drug treatment to 
lower the level 
• 
An increase in an enzyme 
(called amylase) that helps 
break down starch and sugars in 
the body 
• 
Numbness and tingling in the 
fingers and toes 
• 
A problem in nerve function 
that may cause pain, numbness, 
tingling, and muscle weakness 
in various parts of the body and 
may affect the ability to 
perform tasks that require fine 
movements  
 
 
Clofibrate 
 
Common 
Serious 
Abdominal pain  
Constipation 
Diarrhea 
Nausea 
Headache 
Rash 
dry skin 
dry hair 
urticaria 
alopecia 
weight gain 
constipation (2%) 
epigastric pain (frequent) 
nausea (10%) 
vomiting (10%) 
diarrhea (10%) 
flatulence (10%) 
Fatigue 
Weakness 
Drowsiness 
dizziness  
headache 
Light intolerance 
Cardiac arrhythmias 
Cardiomyopathy (very rare) 
Peripheral vascular disease (rare) 
pulmonary embolism (rarae) 
thrombophlebitis (rare) 
angina pectoris (rare) 
cardiac arrhythmias (rare) 
cardiomyopathy 
cardiomegaly 
intermittent claudication  
Thrombophlebitis 
Pruritus 
erythema multiforme 
toxic epidermal necrolysis 
Stevens-Johnson Syndrome 
Fevers 
gallstones 
Pancreatitis (rare) 
Leukopenia (rare) 
Anemia (rare) 
Eosinophilia (rare) 
 Agranulocytosis (rare) 
increase in liver transaminases  

 
 
 
 
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Lethargy 
Somnolence 
tiredness 
Systemic lupus erythematosus 
Drug-induced myopathy 
flu-like symptoms (rare) 
myositis (rare) 
arthralgia (rare) 
rhadomyolysis (rare) 
mood disorders 
cognitive disorders 
sleep disorders 
perception disorders 
 
Impotence 
decreased libido 
dysuria 
hematuria 
proteinuria 
renal failure 
 
 
Clomipramine 
Adverse Effects 
Serious:  
• 
Cardiovascular: Cardiac arrest, Orthostatic hypotension (4% to 6%), Prolonged QT 
interval, Syncope (2%) 
• 
Endocrine metabolic: Hyperglycemia, Increased body temperature 
• 
Hematologic: Agranulocytosis, Leukopenia, Pancytopenia, Thrombocytopenia 
• 
Hepatic: Hepatotoxicity (1% to 3%) 
• 
Neurologic: Seizure (0.7%), Serotonin syndrome, Neuromuscular blockade 
• 
Psychiatric: Suicidal thoughts, Suicide 
 
Common: 
• 
Dermatologic: Diaphoresis (9% to 29%) 
• 
Endocrine metabolic: Weight increased (18%) 
• 
Gastrointestinal: Constipation (22% to 47%), Diarrhea (13%), Indigestion (13% to 22%), 
Loss of appetite (12% to 22%), Nausea (33%), Xerostomia (63%% to 84%) 
• 
Musculoskeletal: Myalgia (13%) 
• 
Neurologic: Dizziness (41% to 54%), Feeling nervous (2% to 18%), Headache (28% to 
52%), Insomnia (11% to 25%), Myoclonus (13%), Somnolence (46% to 54%), Tremor 
(33% to 54%) 
• 
Ophthalmic: Abnormal vision (7% to 18%) 
• 
Renal: Disorder of the urinary system (14%) 
• 
Reproductive: Disorder of ejaculation (6% to 42%), Impotence (20%), 
Respiratory: Pharyngitis (14%) 
• 
Other: Fatigue (35% to 39%) 
 
 

 
 
 
 
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Clonidine 
Adverse Effects 
Serious:  
• 
Cardiovascular: Atrioventricular block, Bradyarrythmia, Rebound Hypertension ,  
 
Common: 
• 
Dermatologic: Contact dermatitis (5% to 47%), Erythema (26%), Pruritus, 
Hyperpigmentation of skin (5%) 
• 
Gastrointestinal: Xerostomia (25%) 
• 
Neurologic: Dizziness (2%), Headache (5%), Sedated (3%), Somnolence (12%) 
• 
Other: Fatigue (6%) 
 
 
Clopidogrel 
 
Common 
Serious 
Chest pain 
Hypertension (4.3%) 
Pruritus (3.3%) 
Purpuric disorder (5.3%) 
Rash (4.2%) 
Hypercholesterolemia 
Abdominal pain  
Constipation  
Diarrhea 
Gastritis 
Indigestion 
Epistaxia (2.9%) 
Purpura (5.3%) 
Arthralgia 
Backache 
Headache (7.6%) 
 
Acute myocardial infarction, rebound effect 
Atrial fibrillation  (1% to 2.5%) 
Congestive heart failure (1% to 2.5%) 
coronary artery stent thrombosis  
erythema multiforme 
Stevens-Johnson syndrome 
Gastrointestinal hemorrhage (2%, 2.7% with aspirin) 
Gastrointestinal ulcer 
Agranulocytosis (<1%)pancytopenia (severe) 
Thrombotic thrombocytopenic purpura (rare) 
Drug-induced liver disorder 
Hepatitis (rare) 
Hepatotoxicity 
Abnormal liver function test (rare) 
Anaphylaxis (rare) 
Abnormal renal function (< 1%) 
Acute renal failure (< 1%) 
Non-cardiogenic pulmonary edema 
 
This drug may cause chest pain, edema, purpuric disorder, abdominal pain, constipation, 
diarrhea, dyspepsia, gastritis, gastrointestinal ulcer, arthralgia, back pain, dizziness, or 
headache. 
 
Instruct patient to report signs/symptoms of bleeding, especially if used concomitantly with 
anticoagulant therapy. 
 
Patient should avoid aspirin or aspirin-containing products during drug therapy unless approved 
by healthcare professional. 
 
 
 
 
 
 

 
 
 
 
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Clotrimazole 
 
Common 
Rare 
Diarrhea (frequent) 
Nausea (frequent) 
Vomiting (frequent) 
Pruritus 
Skin irritation (topical application) 
Abnormal liver enzymes 
Depression  
Drowsiness 
Disorientation 
Vision changes 
Erythema 
Stinging 
Burning  
Urticaria 
Edema  
Loss of appetite 
Urinary frequency 
Lower abdominal cramps 
Dyspareunia 
• 
Oral form may cause nausea or vomiting. 
• 
Advise patients using the intravaginal formulation to not use tampons during treatment. 
• 
Instruct patients using the topical formulation to not use occlusive dressings over the 
treated area. 
• 
Patient should avoid douches or other intravaginal products during drug therapy. 
Clozapine 
 
Common 
Serious 
Hypotension 
Tachyarrhythmia (25%) 
Rash (2%) 
Sweating symptom (6%) 
Excessive salivation (31%) 
Nausea (5%) 
Xerostomia (6%) 
Motor function behavior changes (4%) 
Muscle rigidity (3%) 
Akathisia (3%) 
Confusion (3%) 
Dizziness (19%) 
Headache (7%) 
Insomnia (2%) 
Somnolence (39%) 
Tremor (6%) 
Vertigo (19%) 
Visual disturbance (5%) 
Agitation (4%) 
Dyssomnia  
Nightmares (4%) 
Restlessness (4%) 
Urinary tract disorder (2%) 
Fatigue (2%) 
Fever (2%) 
Cardiac arrest (rare) 
Myocarditis 
Orthostatic hypotension 
Pericardial effusion (rare) 
Sudden cardiac death  
Syncope (5%) 
Hyperglycemia (rare) 
Bowel obstruction  
Colitis 
Necrotizing 
Fecal impaction 
Gastrointestinal hypomotility  
Ischemic bowel disease 
Pancreatitis 
Paralytic ileus 
Perforation of intestine 
Agranulocytosis (1.3%) 
Drug-induced eosinophilia (1%) 
leucopenia  
neutropenia (3%) 
thrombocytopenia (rare) 
decreased white blood cells 
hepatitis (rare) 
neuroleptic malignant syndrome 
seizure (5%) 
tardive dyskinesia (rare) 
pulmonary embolism (rare) 
respiratory arrest (rare) 

 
 
 
 
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death 
• 
Patient should avoid activities requiring mental alertness or coordination until drug 
effects are realized. 
• 
This drug may cause anticholinergic symptoms, hypotension, sweating, abdominal 
discomfort, excessive salivation, nausea, headache, tremor, vertigo, dyssomnia, fever, 
orthostatic hypotension, syncope, or seizure. 
• 
May cause hypotension, especially with first dose and with dose adjustments. 
• 
Drug may also cause neuroleptic malignant syndrome (sweating, fever, stupor, unstable 
blood pressure, muscular rigidity, autonomic dysfunction). 
• 
Instruct patient to report signs/symptoms of hyperglycemia. 
• 
Advise patient to report signs/symptoms of infection, as drug can cause leukopenia. 
• 
Instruct patient to report signs/symptoms of heart failure, myocarditis, or 
cardiomyopathy. 
• 
Patient should report signs/symptoms of extrapyramidal effects or tardive dyskinesia 
(jerky muscle movements, tongue thrusting, facial grimacing/ticks, random movements 
of extremities), especially when taking high doses or with prolonged treatment. 
• 
Advise patient against sudden discontinuation of drug. 
• 
Encourage patient to maintain adequate hydration during drug therapy. 
• 
If dose has been missed for more than two days, advise patient to consult healthcare 
professional for instructions as dose may not be the same. 
 
 
Colchicine 
Adverse Effects 
Serious:  
• 
Hematologic: Myelosuppression 
 
Common: 
• 
Gastrointestinal: Diarrhea (high dose, 77%; low-dose, 23%), Nausea (high dose, 17%; 
low-dose, 4%), Vomiting (17%) 
 
 
Cortisone 
 
Adverse Effects 
Serious:  
• 
Endocrine metabolic: Hyperglycemia, Primary adrenocortical insufficiency 
• 
Musculoskeletal: Osteoporosis 
• 
Ophthalmic: Cataract, Glaucoma 
 
Common: 

 
 
 
 
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• 
Cardiovascular: Hypertension 
• 
Dermatologic: Atrophic condition of skin, Finding of skin healing, Impaired 
• 
Endocrine metabolic: Cushing's syndrome, Decreased body growth 
• 
Gastrointestinal: Disorder of gastrointestinal tract 
• 
Immunologic: At risk for infection 
• 
Psychiatric: Depression, Euphoria 
 
Crizotinib 
 
Common  >10%: 
• 
Cardiovascular: Edema (28%) 
• 
Central nervous system: Fatigue (20%), dizziness (16%) 
• 
Gastrointestinal: Nausea (53%), diarrhea (43%), vomiting (40%), constipation (27%), 
appetite decreased (19%), taste alteration (12%), esophageal disorder (11%; includes 
dyspepsia, dysphagia, epigastric burning/discomfort/pain, esophageal 
obstruction/pain/spasm/ulcer, esophagitis, gastroesophageal reflux, odynophagia, reflux 
esophagitis) 
• 
Hematologic: Lymphopenia (grades 3/4: 11%) 
• 
Hepatic: ALT increased (13%; grades 3/4: 5%) 
• 
Neuromuscular & skeletal: Neuropathy (13%; grades 3/4: <1%) 
• 
Ocular: Vision disorder (62%; onset: <2 weeks; includes blurred vision, diplopia, 
photophobia, photopsia, visual acuity decreased, visual brightness, visual field defect, 
visual impairment, vitreous floaters) 
 
Rare/Occasional 1% to 10%: 
• 
Cardiovascular: Bradycardia (5%), chest pain (1%) 
• 
Central nervous system: Headache (4%), insomnia (3%) 
• 
Dermatologic: Rash (10%) 
• 
Gastrointestinal: Abdominal pain (8%), stomatitis (6%) 
• 
Hematologic: Neutropenia (grades 3/4: 5%) 
• 
Hepatic: AST increased (9%; grades 3/4: 2%) 
• 
Neuromuscular & skeletal: Arthralgia (2%) 
• 
Renal: Renal cysts (1%) 
• 
Respiratory: Cough (4%), dyspnea (2%), pneumonitis (2%), upper respiratory infection 
(2%) 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Cyanocobalamin 
 
 
Common 
 
Occasional 
 
Rare 
Immediate:  
Within 1-2 
days of 
receiving drug  
 
Injection site pain  
Skin rash, pruritis, urticaria, 
diarrhea, anaphylaxis, hypokalemia 
(secondary to erythrocyte production 
in severe megaloblastic anemia)  
Prompt:  
Within 2-3 
weeks, 
prior to 
next course  
 
 
Optic atrophy in Leber’s disease  
Delayed:  
Any time 
later during 
therapy, 
excluding the 
above 
conditions  
 
 
Pulmonary edema, congestive heart 
failure, peripheral vascular 
thrombosis, unmasking of 
polycytemia vera  
Unknown 
Frequency 
and Timing:  
 
Fetal and teratogenic toxicities: Vitamin B-12 crosses the placenta. Vitamin B12 is an essential 
vitamin and requirements are increased during pregnancy. Amounts of Vitamin B12 that are 
recommended by the Food and Nutrition Board, National Academy of Science-National  
Research Council for pregnant women (4 mcg daily) should be consumed during pregnancy.  
Vitamin B12 is distributed into breast milk. The American Academy of Pediatrics considers its use to be usually 
compatible with breast feeding.  
1The product may contain aluminum which can accumulate in patients with renal dysfunction and 
premature infants. The product may contain benzyl alcohol dependent upon the manufacturer and 
should be avoided in premature infants. 
 
CYCLOPHOSPHAMIDE:  
 
 
 
Common 
 
Occasional 
 
Rare 
Immediate: Loss of appetite (L), nausea (L), 
vomiting (L) 
Metallic taste (L), abnormal 
hormone function affecting 
levels of salt in the blood and 
urine, causing too much or too 
little urine1 
Temporary blurred vision1, heart 
damage with abnormal heart 
rhythms1, decay of muscle tissue 
in the heart2 
Within 2-3 
wks: 
Decrease in the number of red and 
white blood cells and platelets 
made in the bone marrow, hair 
loss 
Bleeding and inflammation of 
the urinary bladder (L) 
 
Delayed: 
decreased ability of the body to 
fight infection or disease, absence 
of sperm or stopped monthly 
periods, inability to have 
children(L) 
 
Damage/scarring of lung tissue 3 
(L) 
Late: 
 
 
Cancer caused by treatment for a 
previous cancer or leukemia, 
damage/scarring of bladder tissue 
Unknown Timing and Frequency:  Abnormalities in unborn and breast-fed children 
• 
 
• 
1 Less common with lower doses. 
• 
2Only with very high doses. 
• 
3 Risk increased in someone who has had chest radiation. 

 
 
 
 
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CYCLOSERINE 
Brand Name(s): Seromycin 
Adverse Effects 
Serious:  
• 
Neurologic: Seizure 
 
Common: 
• 
Neurologic: Confusion, Dizziness, Headache, Somnolence 
 
Patient Information 
• 
Patient should avoid activities requiring mental alertness or coordination until drug effects 
are realized. 
• 
This drug may cause confusion, dizziness, headache, somnolence, or seizure. 
• 
Instruct patient to report depression, suicidal ideation, or unusual changes in behavior. 
• 
Advise patients receiving daily doses greater than 500 mg to monitor for and report 
signs/symptoms of CNS toxicity. 
• 
Patient should not drink alcohol while taking this drug. 
 
Contraindications 
• 
hypersensitivity to cycloserine 
• 
epilepsy (current or history of) 
• 
depression, anxiety, psychosis (current or history of) 
• 
severe renal insufficiency (creatinine clearance less than 50 mL/min) 
• 
alcohol abuse 
 
Precautions 
• 
None indicated 
 
 
 

 
 
 
 
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CYCLOSPORIN 
Brand Name(s): Gengraf  ;  Neoral  ;  Restasis  ;  Sandimmune 
Adverse Effects 
Serious:  
• 
Endocrine metabolic: Hyperkalemia, Hypomagnesemia 
• 
Hepatic: Hepatotoxicity (7% or less) 
• 
Immunologic: Infectious disease 
• 
Neurologic: Coma, Encephalopathy, Leukoencephalopathy, Seizure (1% to 5%) 
• 
Renal: Hemolytic uremic syndrome, Nephrotoxicity (25% to 38%) 
 
Common: 
• 
Cardiovascular: Hypertension (13% to 53%) 
• 
Dermatologic: Hirsutism (21% to 45%) 
• 
Gastrointestinal: Drug-induced gingival hyperplasia (4% to 16%) 
• 
Neurologic: Headache (2% to 15%), Tremor (12% to 55%) 
• 
Ophthalmic: Burning sensation in eye (17%) 
 
Patient Information 
• 
Patient should not use ophthalmic preparation in an infected eye . 
• 
Advise patient to avoid vaccines during therapy unless approved by a healthcare 
professional . 
• 
To decrease the risk of skin malignancies, advise patient to avoid excessive exposure to 
ultraviolet light . 
• 
Drug may cause hypertension, renal dysfunction, hirsutism, diarrhea, nausea, vomiting, 
headache, tremor, or gingival enlargement . 
• 
The ophthalmic preparation may cause a foreign body or burning sensation in the eye . 
• 
Instruct patient to report signs/symptoms of transplant rejection or infection . 
• 
Advise patient to report signs/symptoms of hepatotoxicity or encephalopathy, especially 
patients receiving high-dose therapy . 
• 
Instruct patients to report signs/symptoms of nephrotoxicity, especially when on 
concomitant nephrotoxic drugs . 
• 
Patients using the ophthalmic preparation should report visual disturbances, conjunctival 
hyperemia, eye pain, or discharge from eye . 
• 
Patient should allow at least 5 minutes between instillation of this drug and other 
ophthalmic products . 
• 
Warn patient that rinsing the oral solution syringe with water either before or after use will 
cause a variation in dose and should be avoided . 
• 
Tell patient to remove contact lenses prior to instilling ophthalmic formulation. Lenses 
may be reinserted 15 minutes following instillation . 
• 
Patient should not eat grapefruit or drink grapefruit juice while taking this drug . 
• 
Patient should avoid concomitant potassium-sparing drugs, potassium supplements, and 
foods/salt substitutes that are high in potassium . 
• 
Tell patient that there are multiple significant drug-drug interactions for this drug. Consult 
healthcare professional prior to new drug use (including over-the-counter and herbal 
drugs) . 
Contraindications 
• 
hypersensitivity to cyclosporine or any of ingredient in the formulation of the product 
including polyoxyethylated castor oil (Cremophor(R) EL) in Sandimmune(R) injection  
• 
ocular infections, active (ophthalmic emulsion)  

 
 
 
 
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Precautions 
• 
multiple immunosuppressant treatment regimens; increased risk for lymphomas, 
malignancies, some fatal, and/or infections  
• 
bioequivalence, Sandimmune(R) and Neoral(R) are NOT bioequivalent; monitoring 
during conversion recommended  
• 
concomitant use with nephrotoxic drugs; increased risk of renal dysfunction  
• 
concomitant use with potassium sparing diuretics should be avoided  
• 
concomitant use with PUVA, UVB or other radiation therapy should be avoided  
• 
encephalopathy, (eg, impaired consciousness, convulsions, visual disturbances, motor 
function loss, movement disorders, psychiatric disturbances); has been reported; most 
cases reversible upon dose reduction or discontinuation  
• 
high dose cyclosporine; increased risk of hepatotoxicity and nephrotoxicity  
• 
hyperkalemia, significant, sometimes associated with hyperchloremic metabolic acidosis; 
has been reported  
• 
hyperuricemia, significant; has been reported  
• 
hypertension; common effect that may require antihypertensive therapy and/or dose 
reduction  
• 
malabsorption conditions; risk of inadequate therapeutic levels with cyclosporine 
capsules or oral suspension  
• 
nephrotoxicity, mild, severe, chronic progressive cyclosporine-associated; has been 
reported  
• 
opportunistic infections (eg, activation of latent viral infections); increased risk associated 
with immunosuppression; BK-virus associated nephropathy may lead to renal allograft 
loss; monitoring and dose adjustment recommended 
• 
optic disc edema, including papilloedema, with possible visual impairment secondary to 
intracranial hypertension; has been reported  
• 
radiation therapy; excessive immunosuppression possible and subsequent risk of 
malignancies  
• 
seizure, particularly with concomitant high-dose methylprednisolone; has been reported  
• 
serious infections; increased risk of; fatalities have been reported  
• 
vaccination; may be less effective; avoid use of live attenuated vaccines during 
cyclosporine therapy  
 
 
 
 

 
 
 
 
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CYPROHEPTADINE HYDROCHLORIDE 
Brand Name(s): Periactin 
Adverse Effects 
Serious:  
• 
Hepatic: Hepatitis 
 
Common: 
• 
Endocrine metabolic: Increased appetite, Weight gain 
• 
Gastrointestinal: Abdominal discomfort, Diarrhea, Nausea, Vomiting, Xerostomia 
• 
Neurologic: Central nervous system depression, Somnolence 
• 
Respiratory: Thick sputum, Bronchial 
 
Patient Information 
• 
Patient should avoid activities requiring mental alertness until drug effects are realized, 
as drug may cause somnolence. 
• 
This drug may cause increased appetite, weight gain, abdominal discomfort, nausea, 
xerostomia, diarrhea, vomiting, or thickened bronchial sputum. 
• 
Advise patient to take with food to minimize gastric irritation. 
• 
Patient should avoid concomitant use of alcohol or other CNS depressants during 
therapy. 
• 
Tell patient to not take concurrent MAO inhibitors, as this may intensify anticholinergic 
effects. 
 
Contraindications 
• 
angle-closure glaucoma 
• 
elderly, debilitated patients 
• 
hypersensitivity to cyproheptadine products 
• 
MAOI therapy 
• 
newborn or premature infants 
• 
nursing mothers 
• 
stenosing peptic ulcer, pyloroduodenal obstruction 
• 
symptomatic prostatic hypertrophy, bladder neck obstruction 
 
Precautions 
• 
avoid use during activities which require mental alertness 
• 
avoid use with alcohol and other central nervous system depressants 
• 
cardiovascular disease 
• 
elderly are more susceptible 
• 
history of bronchial asthma 
• 
hypertension 
• 
hyperthyroidism 
• 
increased intraocular pressure 
may cause drowsiness in adults and excitation in children 
 
 
 
 
 

 
 
 
 
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Cytarabine 
 
Risks and side effects related to cytarabine include those which are: 
Likely 
Less Likely 
Rare but serious 
• 
Nausea and 
vomiting  
• 
Hair loss 
• 
Mouth sores 
• 
Loss of desire to eat 
• 
Fewer red and white 
blood cells and 
platelets in the 
blood  
o 
a low number of 
red blood cells 
can make you 
feel tired and 
weak 
o 
a low number of 
white blood 
cells can make it 
easier to get 
infections 
o 
a low number of 
platelets causes 
you to bruise 
and bleed more 
easily 
o 
Redness, pain 
and 
inflammation of 
the eye with 
higher doses 
 
 
• 
Rash 
• 
Severe rash with redness 
and pain on the palms of 
the hand and soles of the 
feet  
• 
Flu type symptoms with 
fever, tiredness, aches 
and pains 
• 
Diarrhea 
• 
Low levels of certain salts 
in the body like 
potassium and calcium 
• 
Difficulty emptying the 
bladder 
• 
High levels of uric acid in 
the blood which could 
damage the kidneys 
• 
With higher doses of 
cytarabine fluid may 
accumulate in the lungs 
making it difficult to 
breathe  
 
• 
Allergic reactions (can be severe 
and life-threatening causing 
difficulty in breathing and or a drop 
in blood pressure) 
• 
A syndrome called Ara-C syndrome 
where there is fever, aches, pains, 
sometimes chest pain, a rash and 
inflammation of the eye 
• 
With higher doses of cytarabine 
there can be effects on the brain 
which can lead to headaches, 
incoordination of the muscles when 
walking, rapid jerky eye movements, 
difficulty with speech, sleepiness, 
personality changes, coma 
• 
With higher does of cytarabine there 
can be effects on the heart which 
can lead to chest pain and damage 
to the heart muscle 
• 
Inflammation or damage to the liver 
which can be severe and life-
threatening and which may lead to 
an enlarged liver and spleen, 
bleeding from the veins in the 
esophagus (the passage that leads 
from the throat to the stomach), a 
yellow appearing skin, and fluid 
collection in the abdomen which 
makes it look larger. 
• 
Kidney Damage 
• 
Muscle breakdown which can lead to 
injury to the kidneys and other 
organs 
 
 
 

 
 
 
 
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Dantrolene 
 
Common 
Serious 
Lightheadedness 
Constipation 
Diarrhea 
Asthenia 
Dizziness 
Headache 
Somnolence 
Diplopia 
Visual disturbance 
Fatigue 
Malaise 
Sun-sensitivity  
Abnormal blood pressure 
Heart failure (infrequent) 
Phlebitis 
Tachyarrhythmia 
Aplastic anemia 
Leukopenia 
Malignant lymphoma (small lymphocytic) 
Thrombocytopenia (infrequent) 
Disease of liver (fatal and non-fatal) 
• 
Drug causes sun-sensitivity. Advise patient to use sunscreen and avoid tanning beds. 
• 
Patient should avoid activities requiring mental alertness or coordination until drug 
effects are realized, as drug may cause light-headedness, dizziness, or somnolence. 
• 
This drug may cause constipation, diarrhea, asthenia, headache, diplopia, visual 
disturbance, fatigue, or malaise. 
• 
Instruct patient to report any difficulties with swallowing. 
 
 
 
Dasatinib 
Likely: 
• 
Low platelet count which may lead to bleeding or bruising 
 
• 
Diarrhea 
 
Less Likely: 
 
• 
Low Blood Counts: low red blood cell count may make you feel tired; low white 
blood cell count increases the risk of infection, fever or pneumonia. 
 
• 
Skin-related: reddening of the face with feelings of warmth; itching; rash with 
peeling of the skin. 
 
• 
Stomach/Intestine-related: loss of appetite; excessive gas in the intestines; 
nausea; vomiting; bloating; loss of water from the body; stomach pain 
 
• 
General: infection; headache; tingling, burning, or prickling sensation; fatigue; 
fever 
 
• 
Laboratory test-related: abnormal liver function; temporary increase in the 
blood of creatinine which may indicate kidney damage 

 
 
 
 
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• 
Risk of Bleeding: there is a risk of bleeding which may be life-threatening.  
Specifically, damage to the intestine may result in bleeding. 
 
• 
Fluid Retention: fluid buildup in the lungs that can make you feel short of breath 
 
 
Rare But Serious: 
 
• 
Damage to the sac around the heart which can lead to a build-up of fluid around 
the heart which may be painful and affect the ability of the heart to work 
normally. 
 
• 
Tumor Lysis Syndrome:  very rapid death of cancer cells releases chemicals 
which may lead to reduced kidney function.  Accumulation of these chemicals 
may harm muscle or nerve function. 
 
Side effects reported by patients, but it is not certain yet if they are related to taking the drug 
Dasatinib: 
 
• 
Low Blood Counts: decrease in the number of immune system cells; low numbers 
of white blood cells called lymphocytes that may last a long time and make it 
easier to get infections which may be life threatening. 
 
• 
Heart-related: a rapid heart rate of over 100 beats per minute; chest pain that 
may mean heart damage; irregular heartbeat; problems with the electrical system 
of the heart; high blood pressure 
 
• 
General: inability to sleep; rigors/chills; changes in your weight 
 
 
• 
Skin-related: an allergic reaction in the blood vessels of the skin which turn the 
skin red, inflamed and bumpy and which may lead to skin breakdown; acne; 
changes in your nails; open sores on the skin; hives; puffiness or swelling around 
the eyes 
 
• 
Stomach/Intestine-related: constipation; dry mouth; inflammation of the small 
intestine; difficulty or discomfort in swallowing; ulcer in the small intestine; 
heartburn; painful mouth sores 
 
• 
Fluid Retention: excess buildup of fluids in body tissues; usually the tissues of 
the head, neck, buttocks, and genital areas 
 
• 
Laboratory test-related: high levels of enzymes in the blood which could affect 
liver, kidney, and heart functions; decrease in the level of magnesium in the 
blood. 
 
• 
Muscle/Joint-related: stiffness of the neck, pain in the muscles and bones; pain 
throughout the body; back pain; pain in the arms and legs.  
 

 
 
 
 
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• 
Nervous system-related: anxiety; depression; dizziness; seizure; damage to a 
nerve of the brain which may affect hearing and balance; a feeling of sleepiness, 
an inability to stay awake or aware or be aroused by someone else. 
 
• 
Breathing-related: shortness of breath; buildup of fluid in the lungs which can 
also make you feel short of breath. 
 
• 
Kidney-related: damage to the kidney that may be serious and life-threatening; 
increased need to urinate 
 
• 
Vein-related: inflammation of a vein; problems with blood clotting which may be 
life-threatening. 
 
 
Daunorubicin 
 
Risks and side effects related to the daunorubicin include: 
 
Common 
Happens to 21-100 
children out of every 
100 
Occasional 
Happens to 5-20 
children out of every 
100 
Rare 
Happens to < 5 children out of 
every 100 
Immediate: 
Within 1-2 days of 
receiving drug 
Nausea, vomiting, pink 
or 
red color to urine, 
sweat, 
tears, and saliva 
Hyperuricemia, sclerosis 
of the vein 
Diarrhea, anorexia, abdominal 
pain, extravasation (rare) but if 
occurs = local ulceration, 
anaphylaxis, fever, chills, rash, 
urticaria, acute  arrhythmias 
Prompt: 
Within 2-3 weeks, 
prior to the next course 
Myelosuppression 
(leukopenia, 
thrombocytopenia, 
anemia), alopecia 
Mucositis (stomatitis 
and 
esophagitis),hepatotoxici
ty 
Radiation recall reactions, 
myocarditis-pericarditis 
syndrome, conjunctivitis and 
lacrimation 
Delayed: 
Any time later during 
therapy 
 
 
Cardiomyopathy1 (uncommon 
at cumulative doses ≤ 550 
mg/m², 400 mg/m² with 
mediastinal radiation, 300 
mg/m² in children, or 10 
mg/kg in children < 2 yrs or 
0.5 m²) (L), hyper-
pigmentation of nail beds 
Late: 
Any time after 
completion of 
treatment 
 
Subclinical cardiac 
dysfunction 
CHF (on long term follow up 
in 
pediatric patients), secondary 
malignancy (in combination 
regimens) 
Unknown 
Frequency and 
Timing: 
Fetal toxicities and teratogenic effects of daunorubicin have been noted in animals. It 
is unknown whether the drug is excreted in breast milk. 
 
 
 
 
 

 
 
 
 
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Decitabine 
While on the study, you are at risk for side effects (see table below). You should discuss these 
with your child’s doctor. If you experience any side effects you may be given other medications 
to make them less serious or uncomfortable. We believe that most side effects will go away 
shortly after treatment with decitabine is stopped, but in some cases side effects may be serious, 
long lasting or permanent. There may also be other side effects that we cannot predict.  There is 
also a small, but real possibility that life-threatening complications, death, or a second cancer may 
occur. 
 
 
Known risks and side effects related to the decitabine include: 
 
Common 
(21-100% Frequency) 
Occasional 
(5-20% Frequency) 
Rare 
(< 5% Frequency) 
Immediate:  Within 1-2 
days of receiving drug 
 
 
Fever with a low white 
blood 
cell 
count 
making 
you 
more 
susceptible to infection 
(potentially 
life-
threatening), 
nausea, 
and vomiting.  
 
Allergic reactions, which 
appear as a rash and bumps. 
Tiredness, peritonitis 
(inflammation in the lining 
of your abdomen, poor 
appetite, difficulty staying 
awake, increased chance of 
liver damage, stomach pain 
or cramping, and diarrhea. 
Prompt:  Within 2-3 
weeks, prior to next 
course. 
Anemia* (making 
you weak and tired), 
low white blood cell 
count which increases 
your risk for infection 
and low platelet 
count* which may 
cause bruising or 
bleeding 
Soreness, and sores in 
mouth or throat. 
Kidney or liver damage 
Delayed:  Anytime after 
above. 
Anemia* (making 
you weak and tired), 
low white blood cell 
count which increases 
your risk for infection 
and low platelet 
count* which may 
cause bruising or 
bleeding  
 
Hair loss. 
 
Late:  Anytime after 
completion of treatment 
 
 
 
Unknown Timing and 
Frequency 
 
 
 
*Patients who develop anemia or low platelet counts may require red blood cell or platelet 
transfusions and as a result transfusion of blood and/or blood components may be necessary. 
Transfusions may be accompanied or followed by fever and/or reactions that can cause kidney 
failure, heart failure, anemia, hepatitis, A.I.D.S. (acquired immune deficiency syndrome) and 
other infections. 
 
Other toxicities that may or may not be related to decitabine have been reported in adult patients.  

 
 
 
 
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These include: allergy, irregular heart beats, blood clots, swelling of veins, decreased blood flow 
to heart, face swelling, low blood pressure, heart attacks, veno-occlusive disease (blood vessels 
that carry blood through the liver become swollen or clogged), build up of fluid in the stomach, 
heart failure, fever, chills,  weight loss, skin rash, itching, inability to taste, constipation, 
inflammation of the gallbladder, blood in the urine, liver failure, increased alkaline phosphatase, 
reactivation of an  
infection caused by the herpes virus,  low levels of salts in the blood, weakness or pain due to 
nerve injury, depression, dizziness, headache, lightheadedness, restlessness, sleep disorder, 
seizures, paralysis of arm/leg on the same side of the body, muscle pain, bone pain, shortness of 
breath, hiccups, fluid in the lungs, difficulty in breathing caused by a collapse of a lung, cough, 
painful urination, kidney failure, and decreased blood flow to brain,  or flow of blood to the 
lungs.    
 
If a person gets pregnant while receiving decitabine, it could be dangerous for the baby.  You 
should not become pregnant or father a baby while on this study.  You should not nurse (breast 
feed) a baby while on this study.  Ask about counseling and more information about preventing 
pregnancy. 
 
 
 
DEFEROXAMINE MESYLATE 
Brand Name(s): Desferal 
Adverse Effects 
Serious:  
• 
Cardiovascular: Cardiac complication, Hypotension, Shock, Tachyarrhythmia 
• 
Immunologic: Immune hypersensitivity reaction (frequent) 
• 
Neurologic: Ototoxicity (frequent) 
• 
Ophthalmic: Eye / vision finding (frequent) 
• 
Other: Mucormycosis (rare) 
 
Common: 
• 
Dermatologic: Injection site pain 
 
Patient Information 
• 
Warn patient that drug may cause a reddish discoloration of the urine. 
• 
If dizziness or vision or hearing impairment are experienced, advise patient to avoid 
driving or performing other hazardous tasks. 
• 
Instruct patient to report signs/symptoms of hypotension or tachyarrhythmia. 
• 
Patient should not use vitamin C concurrently, unless approved by healthcare 
professional. 
 
Contraindications 
• 
anuria  
• 
hypersensitivity to deferoxamine mesylate  
• 
renal disease, severe  
 
Precautions 
• 
aluminum overload, comorbid; may result in decreased serum calcium and aggravation of 
hyperparathyroidism  

 
 
 
 
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• 
dialysis and comorbid aluminum-related encephalopathy; may cause neurological 
dysfunction (seizures) or dialysis dementia  
• 
ferritin levels, low; ocular disturbances (blurry vision; cataracts in chronic iron overload; 
decreased visual acuity; impaired peripheral, color, and night vision; optic neuritis, 
cataracts, corneal opacities, and retinal pigmentary abnormalities) and auditory 
disturbances (tinnitus and hearing loss including high frequency sensorineural hearing 
loss), reversible in most cases, have been reported; monitoring recommended  
• 
geriatric patients; may have an increased risk of ocular and auditory disturbances, 
including deafness and hearing loss; dose adjustment recommended  
• 
high-dose therapy; ocular (blurry vision; cataracts in chronic iron overload; decreased 
visual acuity; impaired peripheral, color, and night vision; optic neuritis, cataracts, corneal 
opacities, and retinal pigmentary abnormalities) and auditory disturbances (tinnitus and 
hearing loss including high frequency sensorineural hearing loss), reversible in most 
cases, have been reported; monitoring recommended  
• 
increased susceptibility to Yersinia enterocolitica, Yersinia pseudotuberculosis; drug 
discontinuation recommended  
• 
IV administration; excessively high doses has resulted in respiratory distress syndrome; 
rapid injection has resulted in urticaria, hypotension, and shock; use proper 
administration  
• 
mucormycosis, including fatalities have been reported; if suspected discontinue therapy 
and institute medical management  
• 
pediatric patients; high doses and concomitant low ferritin levels have been associated 
with growth retardation; monitoring recommended  
• 
prolonged use; ocular (blurry vision; cataracts in chronic iron overload; decreased visual 
acuity; impaired peripheral, color, and night vision; optic neuritis, cataracts, corneal 
opacities, and retinal pigmentary abnormalities) and auditory disturbances (tinnitus and 
hearing loss including high frequency sensorineural hearing loss), reversible in most 
cases, have been reported; monitoring recommended  
• 
renal toxicity, including increases in serum creatinine (possibly dose-related), acute renal 
failure, and renal tubular disorders, has been reported; monitoring recommended  
• 
scintigraphy with gallium-67; imaging may be distorted; discontinue deferoxamine 48 
hours prior to procedure is recommended  
 
Deferoxamine 
 
Common 
Serious 
Injection site pain 
Abdominal discomfort 
Vomiting 
diarrhea 
Cardiac complication 
Hypotension 
Shock 
Tachyarrhythmia 
Immune hypersensitivity reaction (frequent) 
Ototoxicity (frequent) 
Eye/vision changes (frequent) 
Mucormycosis (rare) 
Rash (rare) 
Seizure (rare 
Renal failure (rare) 
Acute respiratory distress (rare) 
• 
Warn patient that drug may cause a reddish discoloration of the urine. 
• 
If dizziness or vision or hearing impairment are experienced, advise patient to avoid 
driving or performing other hazardous tasks. 

 
 
 
 
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• 
Instruct patient to report signs/symptoms of hypotension or tachyarrhythmia. 
• 
Patient should not use vitamin C concurrently, unless approved by healthcare 
professional. 
Demecolcine Sodium 
 
Common 
Serious 
Application site reaction (gel: all reactions, 7%; 
dermatitis, 4% to 11%) 
Blood coagulation disorder (1% to 10%) 
Burning sensation in eye (15%) 
Keratitis (up to 28%) 
Lacrimation and lacrimal drainage – finding ( up 
to 30%) 
Raised intraocular pressure (up to 15%) 
 
Congestive heart failure 
Hypertension 
Myocardial infarction (rare) 
Thrombotic tendency observations  
Erythema multiforme (rare) 
Generalized exfoliative dermatitis (rare) 
Stevens-Johnson syndrome (rare) 
Toxic epidermal necrolysis (rare) 
Gastrointestinal hemorrhage 
Gastrointestinal perforation 
Gastrointestinal ulcer (1% to 10%) 
Inflammatory disorder of digestive tract 
Melena pancreatitis (rare) 
Agranulocytosis (rare) 
Aplastic anemia (rare) 
Hemolytic anemia (rare) 
Hepatic necrosis 
Liver failure (rare) 
Anaphylactoid reaction (rare) 
Cerebrovascular accident 
Meningitis (rare) 
Seizure (rare) 
Acute renal failure 
Papillary necrosis 
Angioedema (rare) 
• 
Advise patient to avoid use in late pregnancy as drug may cause premature closure of 
ductus arteriosus. 
• 
The topical formulation of this drug can cause sun-sensitivity. Advise patient to avoid 
exposure to sunlight and tanning beds. 
• 
This drug may cause edema, abdominal pain, constipation, diarrhea, dyspepsia, 
flatulence, nausea, dizziness, headache, bronchospasm, or tinnitus. The ophthalmic 
formulation may also cause a burning sensation, conjunctivitis, corneal 
deposit/opacity/edema, or discharge from eye. The topical formulation may also cause 
application site skin reactions. 
• 
Advise patient to report signs/symptoms of serious cardiovascular thrombotic events such 
as myocardial infarction or stroke. 
• 
Instruct patient to report signs/symptoms of serious gastrointestinal adverse events such 
as bleeding, ulceration, and perforation of stomach or intestines. 
• 
Instruct patient to report signs/symptoms of hepatotoxicity (nausea, fatigue, lethargy, 
pruritus, jaundice, right upper quadrant tenderness, and flu-like symptoms). 
• 
Patient should promptly report skin rash, blistering, or any symptoms of a serious skin 
reaction. 

 
 
 
 
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• 
Patient should take tablet with a full glass of water, food, or milk to minimize gastric 
irritation. 
• 
Instruct patient on proper instillation technique of ophthalmic formulation. 
• 
Tell patient using ophthalmic form to avoid wearing soft contact lenses during drug 
therapy. 
• 
Instruct patient using topical form to avoid applying this drug to open wounds, infections, 
or inflamed areas and to avoid contact of this drug with eyes and mucous membranes  
• 
Patient should avoid showering, bathing or washing any area where drug is applied, 
including treated hands, for at least one hour after topical application of this drug. 
• 
Patient should not use occlusive dressing or external heat over areas treated with the 
topical formulation. 
• 
Patient should not drink alcohol while taking oral form of this drug. 
• 
Tell patient to avoid use of additional NSAIDs during therapy, unless approved by 
healthcare professional. 
• 
Patient using ophthalmic form should not use other ophthalmic medications, unless 
approved by healthcare professional. 
• 
Advise patient to avoid concomitant use of the topical form of this drug with other topical 
products, including sunscreens, cosmetics, lotions, moisturizers and insect repellants. 
 
DEXTROMETHORPHAN HYDROBROMIDE 
Brand Name(s): Delsym 
Adverse Effects 
Serious:  
• 
None indicated 
 
Common: 
• 
Neurologic: Dizziness (mild), Somnolence (mild) 
• 
Other: Fatigue (mild) 
 
Patient Information 
• 
Instruct patient to report use of a MAO inhibitor within the last 14 days prior to initiating 
therapy. 
• 
Patient should avoid activities requiring mental alertness or coordination until drug effects 
are realized. 
• 
This drug may cause dizziness, somnolence, or fatigue. 
 
Contraindications 
• 
hypersensitivity to dextromethorphan or levorphanol 
• 
Coadministration with monoamine oxidase inhibitors 
 
Precautions 
• 
Not to be used for chronic, persistent cough accompanying a disease state or for cough 
associated with excessive secretions 
• 
Cough accompanied by other symptoms (fever, rash, headache, nausea, vomiting) to be 
treated with DEXTROMETHORPHAN only under medical supervision 
 
 
 
 

 
 
 
 
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DIAZOXIDE 
Brand Name(s): Hyperstat ; Proglycem 
Adverse Effects 
Serious:  
• 
Cardiovascular: Cardiac arrest, Congestive heart failure 
• 
Endocrine metabolic: Diabetic ketoacidosis 
• 
Gastrointestinal: Bowel obstruction, Pancreatitis 
• 
Hematologic: Thrombocytopenia 
• 
Ophthalmic: Optic nerve infarction 
 
Common: 
• 
Cardiovascular: Hypotension (7%) 
• 
Endocrine metabolic: Hyperglycemia 
• 
Gastrointestinal: Nausea and vomiting (4%) 
• 
Neurologic: Asthenia, Dizziness (2%) 
 
Patient Information 
• 
Instruct patient to rise slowly from a sitting/supine position, especially if patient is taking 
concurrent diuretics. 
• 
This drug may cause angina, palpitations, tachyarrhythmia, hirsutism, abdominal pain, 
constipation, diarrhea, loss of appetite, loss of taste, nausea, vomiting, and dizziness. 
• 
Drug may also cause serious adverse effects such as congestive heart failure, bowel 
obstruction, or extrapyramidal disease. 
• 
Tell patient to report signs/symptoms of hyperglycemia, infection, unusual 
bleeding/bruising, or fluid retention. 
• 
Advise diabetic patients to regularly monitor urine for sugar and ketones and to 
immediately report abnormal findings. 
• 
If injectable formulation is used, advise patient to report signs/symptoms of extravasation 
immediately. 
• 
Patient should remain supine for at least 1 h after IV injection, as drug may cause 
hypotension. 
 
Contraindications 
• 
functional hypoglycemia  
• 
hypersensitivity to diazoxide or to other thiazides  
 
Precautions 
• 
cardiac reserve, compromised; risk of congestive heart failure  
• 
concomitant use of coumarin (or its derivatives), diphenylhydantoin, or thiazides (or other 
diuretics); use with caution  
• 
gout, history  
• 
hyperuricemia  
• 
ketoacidosis and nonketotic hyperosmolar coma have been reported  
• 
newborns with increased bilirubinemia; diazoxide may displace bilirubin from albumin  
• 
prolonged treatment; regular monitoring of urine for sugar and ketones is required  
• 
renal function, impaired; risk of drug toxicity  
 
 

 
 
 
 
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Dexamethasone 
 
Risks and side effects related to dexamethasone include those which are: 
Likely 
Less Likely 
Rare But Serious 
• Overeating 
• Difficulty sleeping or 
falling asleep 
• Decreased ability of 
the body to fight 
infection  
• Personality changes 
with mood swings 
• Changes in hormone 
production that cause 
weight gain 
especially around the 
abdomen and 
shoulders, puffy 
cheeks, muscle 
weakness and make 
your body less able 
to deal with stress 
• Pimples 
• Damage to the joints which can result in 
pain and loss of motion usually involving 
the joints of the hip and knee* 
• Red face 
• Fluid retention 
• Wounds don’t heal as well 
• Slowed growth 
• Upset and irritated stomach with heartburn 
• Stomach ulcers 
• High blood sugar which may require 
treatment 
• Stretch marks and easy bruising of the skin 
• Abnormal amounts of uric acid in the blood 
• Increased pressure in the eyes 
• High blood pressure 
• Lessening of calcium in the bones making 
them more susceptible to fracture 
• Cataracts which are usually more reversible 
in children 
• Headache 
• Dizziness 
• Kidney stones that may cause back, 
stomach or pelvic pain and /or may lead to 
the appearance of blood in the urine 
• Inflammation of the 
pancreas 
• Stomach and intestinal 
tract bleeding from 
ulcers 
• Infections 
• Increased pressure in 
the brain which can 
lead to difficulty 
seeing, pressure in the 
eyes and headache  
• Bone fractures 
• Serious changes in 
mood, personality 
and/or severe 
depression 
* This effect happens less often in patients less than 10 years of age. 
 
Steroid drugs, such as dexamethasone (and less frequently prednisone), are known causes of a 
disease called “osteonecrosis” (ON). Osteonecrosis results from the temporary or permanent loss 
of the blood supply to the bones. Without blood, the bone tissue dies and causes the bone to 
breakdown. ON is most commonly seen in the hip joint. If the bones near a joint breakdown it can 
cause the joint to collapse. ON can cause pain and if severe, the patient may need to have surgery. 
The exact reason why corticosteroids cause ON is not known. 
 
 
 
DICLOXACILLIN SODIUM 
Brand Name(s): Dycill ; Dynapen ; Pathocil 
Adverse Effects 
Serious:  
• 
Gastrointestinal: Hemorrhagic colitis 
• 
Hepatic: Hepatotoxicity 
• 
Immunologic: Anaphylaxis (0.015% to 0.04%) 
• 
Renal: Nephrotoxicity 
 
Common: 

 
 
 
 
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• 
Gastrointestinal: Diarrhea, Nausea, Vomiting 
 
Patient Information 
• 
Drug may cause nausea, vomiting, diarrhea, stomatitis, or black tongue. 
• 
Patient should take drug 1 h before or 2 h after meals. 
 
Contraindications 
• 
hypersensitivity to penicillins 
 
Precautions 
• 
hypersensitivity to cephalosporins 
 
 
 
 
DILTIAZEM HYDROCHLORIDE 
Brand Name(s): Cardizem ; Cartia ; Dilacor ; Tiazac ; Taztia 
Adverse Effects 
Serious:  
• 
Cardiovascular: Congestive heart failure (less than 2%), Heart block, Myocardial 
infarction 
• 
Hepatic: Hepatotoxicity 
 
Common: 
• 
Cardiovascular: Bradyarrhythmia (1.7% to 3.6%), Peripheral edema (4.6% to 8%) 
• 
Neurologic: Dizziness (3.5% to 6.4%), Headache (4.6%) 
• 
Respiratory: Cough (2%) 
• 
Other: Fatigue (4.8%) 
 
Patient Information 
• 
Patient should avoid activities requiring coordination until drug effects are realized, as 
drug may cause dizziness. 
• 
This drug may cause gingival hyperplasia, headache, or dermatologic reactions such as 
exfoliative dermatitis (reddened skin, skin peeling/flaking) or erythema multiforme (flu-like 
symptoms, spreading red rash, may progress to more severe form with blistering). 
• 
Instruct patient to report symptomatic hypotension, bradyarrhythmia, peripheral edema, 
or syncope. 
• 
Advise patient against sudden discontinuation of drug. 
• 
This drug is available in multiple brand names with varying properties by brand. Instruct 
patient to follow administration instructions specific to the prescribed brand with regards 
to meals and timing. 
• 
Patient should avoid concomitant use of beta-blockers or digitalis during drug therapy, 
unless otherwise directed by healthcare professional. 
• 
Patient should not drink alcohol while taking this drug. 
 
Contraindications 
• 
acute MI with pulmonary congestion on x-ray (Oral only)  
• 
administration of IV beta-blockers within a few hours of IV diltiazem  

 
 
 
 
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• 
atrial fibrillation or flutter associated with an accessory bypass tract (Wolff-Parkinson-
White or short PR syndromes); risk of potentially fatal heart rate fluctuations (IV only)  
• 
cardiogenic shock (IV only)  
• 
heart block, second or third-degree atrioventricular without a functioning ventricular 
pacemaker  
• 
hypersensitivity to diltiazem  
• 
hypotension, symptomatic (90 mmHg or less systolic)  
• 
newborns; some injections contain benzyl alcohol (IV only)  
• 
sick sinus syndrome without a functioning ventricular pacemaker  
• 
ventricular tachycardia; may lead to hemodynamic deterioration and ventricular fibrillation 
(IV only)  
 
Precautions 
• 
coadministration with other drugs known to decrease peripheral resistance, intravascular 
volume, or myocardial contractility or conduction (IV only)  
• 
concomitant use of beta blockers or digitalis; additive effect on heart rate (Oral only)  
• 
dermatologic reactions leading to erythema multiforme and/or exfoliative dermatitis have 
been reported  
• 
hepatic impairment; increased risk of toxicity  
• 
hypotension  
• 
renal impairment; increased risk of toxicity  
• 
supraventricular arrhythmias with hemodynamic compromise (IV only)  
• 
ventricular function, impaired; worsening congestive heart failure has been reported  
 
 
DIPHENHYDRAMINE HYDROCHLORIDE 
Brand Name(s): Antitussive ; Beldin ; Belix ; Benadryl ; Benylin ; Dibenil ; Diphen ; 
Hydramine ; Silphen ; Vicks Formula 44 
Adverse Effects 
Serious:  
• 
Immunologic: Anaphylaxis 
 
Common: 
• 
Gastrointestinal: Xerostomia 
• 
Neurologic: Dizziness, Dyskinesia, Sedated 
• 
Psychiatric: Somnolence 
• 
Respiratory: Nasal mucosa dry, Pharyngeal dryness, Thick sputum, Bronchial 
 
Patient Information 
• 
Young children may experience a paradoxical excitation effect. 
• 
Patient should avoid activities requiring mental alertness or coordination until drug effects 
are realized, as drug may cause drowsiness. 
• 
This drug may cause anticholinergic effects. Elderly patients may be more susceptible to 
these effects. 
• 
Patient should not use topical form on eyes or eyelid. 
• 
Instruct patient to avoid applying occlusive dressings, cosmetics, or other skin products 
over areas treated with topical formulation. 
• 
Patient should avoid concomitant use of MAO inhibitors or CNS depressants. 

 
 
 
 
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• 
Patient should not drink alcohol while taking this drug. 
 
Contraindications 
• 
hypersensitivity to diphenhydramine 
• 
newborns or premature infants 
• 
nursing mothers 
 
Precautions 
• 
bladder neck obstruction 
• 
concurrent MAOI therapy 
• 
concurrent use of central nervous system depressants 
• 
decreases mental alertness and psychomotor performance 
• 
do not use topical form on eyes or eye lids 
• 
elderly are more susceptible to the side effects of diphenhydramine 
• 
history of bronchial asthma, increased intraocular pressure, hyperthyroidism, 
cardiovascular disease or hypertension 
• 
may cause excitation in young children 
• 
narrow angle glaucoma 
• 
pyloroduodenal obstruction 
• 
stenosing peptic ulcer 
• 
symptomatic prostatic hypertrophy 
• 
use of the topical form on patients with chicken pox, measles, blisters, or large areas of 
skin unless directed by a physician 
 
 
 
 

 
 
 
 
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DIPYRIDAMOLE 
Brand Name(s): Persantine 
Adverse Effects 
Serious:  
• 
Cardiovascular: Angina, Exacerbation with IV (19.7%), Myocardial infarction (rare), 
Ventricular arrhythmia (rare) 
• 
Respiratory: Bronchospasm (rare) 
 
Common: 
• 
Cardiovascular: Electrocardiogram abnormal (15.9%), Hypotension, IV (4.6%) 
• 
Gastrointestinal: Abdominal discomfort, Oral (6.1%), Nausea, IV (4.6%) 
• 
Neurologic: Dizziness (12%), Headache, IV (12.2%), Headache, Oral (2.3%) 
 
Patient Information 
• 
Patient should avoid activities requiring mental alertness or coordination until drug effects 
are realized. 
• 
This drug may cause abdominal discomfort or dizziness. The IV formulation may also 
cause headache or an exacerbation of angina. 
• 
Advise patient to take oral formulation on an empty stomach 1 h before or 2 h after 
meals. If gastric irritation occurs, tell patient to take drug with food or milk. 
• 
Patient should avoid caffeine prior to cardiac stress testing. 
 
Contraindications 
• 
hypersensitivity to dipyridamole  or any other product component  
 
Precautions 
• 
anaphylactoid reactions have been reported (IV)  
• 
asthma, history; may be at increased risk for bronchospasm; IV aminophylline may be 
administered (IV)  
• 
cardiac impulse abnormalities; may be at increased risk for asystole, sinus node arrest, 
sinus node depression, and conduction block (IV)  
• 
asystole, sinus node arrest, sinus node depression, and conduction block have been 
reported; risk may be increased with cardiac impulse formation/conduction abnormalities 
or severe coronary artery disease (IV)  
• 
bronchospasm has been reported (IV)  
• 
cardiovascular events, serious and some fatal (including cardiac death, myocardial 
infarction, ventricular fibrillation, symptomatic ventricular tachycardia, stroke, transient 
cerebral ischemia), have been reported (IV)  
• 
chest pain, severe; monitoring recommended; IV aminophylline and SL nitroglycerin may 
be needed (IV)  
• 
coronary artery disease (unstable angina or recently sustained myocardial infarction), 
severe; chest pain may be aggravated due to vasodilatory effect of dipyridamole (oral) ; 
may also be at increased risk for asystole, sinus node arrest, sinus node depression, and 
conduction block (IV)  
• 
hepatic insufficiency; hepatic enzyme elevations and hepatic failure have been reported 
(oral)  
• 
hypotension; may produce peripheral vasodilation (oral)  
• 
seizures have been reported (IV)  
• 
unstable angina, history; may be at greater risk for severe myocardial ischemia (IV)  
 
 

 
 
 
 
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DISOPYRAMIDE PHOSPHATE 
Brand Name(s): Norpace 
Adverse Effects 
Serious:  
• 
Cardiovascular: Congestive heart failure, Heart block, Hypotension, Prolonged QT 
interval, Torsades de pointes 
• 
Endocrine metabolic: Hypoglycemia (rare) 
• 
Hematologic: Agranulocytosis (rare), Thrombocytopenia (rare) 
• 
Hepatic: Hepatotoxicity (rare) 
 
Common: 
• 
Cardiovascular: Negative inotropic effect on myocardium 
• 
Gastrointestinal: Constipation (11%), Nausea (3% to 9%), Xerostomia (32%) 
• 
Musculoskeletal: Muscle weakness 
• 
Ophthalmic: Blurred vision (3% to 9%) 
• 
Renal: Delay when starting to pass urine (14% to 23%), Urinary retention (3% to 9%) 
• 
Other: Generalized aches and pains (3% to 9%), Malaise and fatigue (3% to 9%) 
 
Patient Information 
• 
Patient should avoid activities requiring coordination until drug effects are realized. 
• 
Instruct patient to rise slowly from a sitting/supine position to minimize dizziness. 
• 
This drug may cause anticholinergic effects, especially xerostomia, urinary hesitancy, 
and constipation. 
• 
Instruct patient to report signs/symptoms of cardiac failure or dysrhythmia. 
• 
Tell patient to report worsening depression, hallucinations, or unusual changes in 
behavior. 
• 
Advise patient against sudden discontinuation of drug. 
• 
Tell patient to not drink alcohol while taking this drug. 
• 
Patient should not take this drug within 48 h before or 24 h after verapamil administration. 
 
Contraindications 
• 
cardiogenic shock 
• 
congenital QT prolongation 
• 
hypersensitivity to disopyramide 
• 
second or third degree AV block 
 
Precautions 
• 
congestive heart failure 
• 
digitalization to be used in patients with atrial fibrillation or flutter prior to disopyramide 
• 
dosage reductions or withdrawal if heart block develops 
• 
ECG abnormalities (ie, QRS widening /QT/QTc prolongation) 
• 
electrolyte abnormalities (ie, hypokalemia/hyperkalemia) 
• 
geriatrics 
• 
glaucoma 
• 
hypoglycemia 
• 
liver disease 
• 
myasthenia gravis 

 
 
 
 
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• 
renal impairment 
• 
sick sinus syndrome/ Wolff-Parkinson-White syndrome/bundle branch block 
• 
urinary retention (including benign prostatic hypertrophy) 
 
DOCETAXEL 
Brand Name(s): Taxotere 
Adverse Effects 
Serious:  
• 
Cardiovascular: Edema (Severe) (6.5% to 8.9%) 
• 
Dermatologic: Stevens-Johnson syndrome, Toxic epidermal necrolysis 
• 
Gastrointestinal: Colitis 
• 
Hematologic: Anemia, less than 8 g/dL (4.3% to 9.2%), Febrile neutropenia (5.2% to 
24.7%), Leukopenia, less than 1000 cells/mm(3) (31.6% to 43.7%), Neutropenia, less 
than 500 cells/mm(3) (65.5% to 85.9%), Thrombocytopenia (8% to 9.2%) 
• 
Hepatic: Hepatotoxicity 
• 
Immunologic: Anaphylaxis (rare) 
• 
Renal: Renal failure 
• 
Respiratory: Interstitial pneumonia, Pulmonary embolism 
• 
Other: Infectious disease (21.6% to 39.4%) 
 
Common: 
• 
Cardiovascular: Edema (47% to 64.1%), Vasodilatation (27%) 
• 
Dermatologic: Alopecia (56.3% to 97.8%), Disorder of nail (11.4% to 18.5%), Disorder of 
skin AND/OR subcutaneous tissue, Nail changes (8.1% to 30.6%), Pruritus, Rash 
• 
Gastrointestinal: Diarrhea (32.8% to 42.6%), Nausea (38.8% to 80.5%), Stomatitis 
(41.7% to 69.4%), Vomiting (22.3% to 44.5%) 
• 
Hematologic: Anemia (89.1% to 93.6%), Leukopenia (95.6% to 98.6%), Neutropenia 
(71.4% to 99.5%) 
• 
Neurologic: Asthenia (61.8% to 80.8%), Neuropathy 
• 
Reproductive: Amenorrhea (61.7%) 
• 
Other: Fever of unknown origin (31.2% to 46.5%) 
 
Patient Information 
• 
Advise patient to avoid vaccines during therapy due to drug-induced immunosuppression. 
• 
This drug may cause edema, alopecia, diarrhea, nausea, stomatitis, vomiting, asthenia, 
fever, or colitis. 
• 
Elderly patients have an increased risk of adverse events. 
• 
Instruct patient to report severe edema or signs/symptoms of myelosuppression, 
hepatotoxicity, or neuropathy (paresthesia, dysesthesia, pain). 
• 
Advise patient to report signs/symptoms of cutaneous toxicity such as Stevens-Johnson 
syndrome (flu-like symptoms, spreading red rash, or skin/mucous membrane blistering) 
or toxic epidermal necrolysis (widespread peeling/blistering of skin). 
 
Contraindications 
• 
neutrophil count less than 1500 cells/mm(3)  
• 
severe hypersensitivity to docetaxel or any other drugs formulated with polysorbate 80  
 
 

 
 
 
 
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Precautions 
• 
fluid retention (eg, peripheral edema, generalized edema, pleural effusion, ascites) has 
occurred; pretreatment with oral corticosteroids recommended prior to each dose  
• 
hepatic impairment; increased risk of severe or life-threatening toxicities; do not use in 
patients in patients with a bilirubin level greater than the ULN or SGOT and/or SGPT 
levels greater than 1.5 x ULN concomitant with an alkaline phosphatase (AP) level 
greater than 2.5 x ULN; monitor LFTs prior to each treatment cycle; dosage adjustment 
recommended for LFT elevations during treatment; discontinue treatment in patients who 
develop AST/ALT levels greater than 5 x ULN and/or AP level greater than 5 x ULN  
• 
hypersensitivity reactions, some cases severe (eg, generalized rash/erythema, 
hypotension, bronchospasm, fatal anaphylaxis), have been reported despite the 
recommended 3 days of corticosteroids premedication  
• 
severe (grade 4) neutropenia has been reported, with some cases associated with 
infection; monitor blood cell counts frequently and for signs of febrile neutropenia or 
neutropenic infections; dose reduction or therapy discontinuation may be warranted; do 
not retreat with subsequent cycles until the neutrophil count is greater than 1500 
cells/mm(3)  
• 
treatment-related mortality has been reported; increased risk in patients with abnormal 
liver function, receiving higher doses, and with non-small cell lung carcinoma and a 
history of prior treatment with platinum-based chemotherapy who receive docetaxel as a 
single agent at a dose of 100 mg/m(2)  
• 
acute myeloid leukemia has been reported rarely in patients with breast cancer who 
received adjuvant therapy with docetaxel, doxorubicin, and cyclophosphamide; 
hematological follow-up recommended in this patient population  
• 
concomitant use with CYP3A4 inhibitors should be avoided; if coadministration with a 
potent CYP3A4 inhibitor is necessary, closely monitor patients for toxicity and consider a 
docetaxel dosage adjustment  
• 
cutaneous toxicity (eg, localized erythema of the extremities with edema followed by 
desquamation) has occurred; dose reduction or therapy discontinuation may be 
warranted if severe skin toxicity develops  
• 
elderly patients (aged 65 yr or older); higher incidence of serious adverse events 
compared with younger patients  
• 
severe neurosensory symptoms (eg, paresthesia, dysesthesia, pain) have been reported; 
dose reduction or therapy discontinuation may be warranted  
• 
severe thrombocytopenia has occurred; monitor blood cell counts frequently; do not 
retreat with subsequent cycles until the platelet count is greater than 100,000 
cells/mm(3)  
• 
report suspected adverse events to Sanofi-Aventis US LLC at 1-800-633-1610 or the US 
Food and Drug Administration at 1-800-FDA-1088 or www.fda.gov/medwatch  
 
 
 
Donepezil Hydrochloride 
 
Common 
Serious 
Hypertension (3%) 
Diarrhea 
Loss of appetite 
Nausea 
Vomiting 
Muscle cramps 
Insomnia 
Atrioventricular block 
Torsades de pointes 

 
 
 
 
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Fatigue 
• 
This drug may cause diarrhea, loss of appetite, nausea, vomiting, muscle cramps, 
insomnia, or fatigue. 
• 
Advise patient that adverse effects may be more frequent at dose escalation and tend to 
resolve with continued use. 
• 
Instruct patient to report signs/symptoms of gastrointestinal bleeding, especially with 
concomitant NSAID use. 
• 
Patient should take in the evening at bedtime. 
Doxorubicin 
 
Risks and side effects related to Doxorubicin include those which are:  
Likely 
Less Likely 
Rare But Serious 
• 
Nausea 
• 
Vomiting 
• 
Temporary hair loss 
• 
Pink or red color to urine, 
sweat, tears, saliva 
• 
Fewer white blood cells, 
red blood cells and 
platelets in the blood. 
○ A low number of red 
blood cells can make 
you feel tired and 
weak 
○ A low number of 
white blood cells can 
make it easier to get 
infections 
○ A low number of 
platelets causes you to 
bruise and bleed more 
easily 
• 
Slight damage to the heart 
muscle that is unlikely to 
have any noticeable 
effects on your heart 
function 
 
• Inflammation and/or sores 
in the mouth (and/or throat 
and /or esophagus, the tube 
that leads from the mouth 
to the stomach) that may 
make swallowing difficult 
and are painful (painful 
mouth sores) 
• Damage to the heart muscle 
which may make you tired, 
weak, feel short of breath, 
and retain fluid 
• Facial Flushing 
• Fever/chills 
• Hives 
• High levels of uric acid in 
the blood which could 
damage the kidneys 
• Dark discoloration of the 
hands, feet and under the 
fingernails with possible 
separation of the nail from 
the nail bed. 
• Damage to the skin if the 
medication leaks from a 
vein 
• Thickening and hardening 
of the veins through which 
the medication is given 
• Reddening reaction of the 
vein through which the 
drug is given. 
• Elevation in the blood of 
certain enzymes found in 
the liver which may 
• 
Severe allergic reaction 
which can be life 
threatening with shortness 
of breath, low blood 
pressure and a rapid heart 
rate  
• 
Ulceration of the lower 
intestinal tract 
• 
An irregular heart beat 
which can be life-
threatening 
• 
Severe damage to the 
heart muscle which may 
lead to severe heart failure 
• 
A new cancer or leukemia 
resulting from this 
treatment. 
 

 
 
 
 
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indicate liver irritation or 
damage. 
• Tearing and inflammation 
of the eyes 
• Loss of appetite 
• Redness and burning at 
sites which have received 
radiation in the past  
• Diarrhea 
The risk of heart damage may be greater in very young children than in older ones.  
 
Doxycycline 
 
Common 
Serious 
Light sensitivity 
Drug-induced gastrointestinal disturbance 
Serum blood urea nitrogen raised 
Loss of appetite 
Nausea 
Vomiting 
Diarrhea 
Esophagitis 
Glossitis 
Dysphagia 
enterocoliti 
Bulding fontanelle (rare) 
• 
Instruct patient to report severe diarrhea and consult healthcare professional prior to 
taking anti-diarrhea medicine. 
• 
Drug causes sun-sensitivity. Advise patient to use sunscreen and avoid tanning beds. 
• 
Drug may decrease effectiveness of oral contraceptives with concurrent use. Recommend 
additional form of birth control. 
• 
This drug may cause a gastrointestinal disturbance. 
• 
Advise patient to take drug with adequate fluid to prevent esophageal irritation or 
ulceration. 
• 
Patient may take tablet and suspension with food, milk, or a carbonated beverage if 
gastric irritation occurs. 
DROPERIDOL 
Brand Name(s): Inapsine 
Adverse Effects 
Serious:  
• 
Cardiovascular: Cardiac arrest, Prolonged QT interval, Torsades de pointes, Ventricular 
tachycardia 
• 
Immunologic: Anaphylaxis 
• 
Neurologic: Neuroleptic malignant syndrome (very rare) 
 
Common: 
• 
Cardiovascular: Hypotension, Tachycardia 
• 
Neurologic: Somnolence, Postoperative 
• 
Psychiatric: Anxiety, Dysphoric mood, Hyperactive behavior, Restlessness 

 
 
 
 
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Patient Information 
• 
his drug may cause extrapyramidal effects, somnolence, anxiety, or dysphoric mood. 
• 
Patient should report signs/symptoms of arrhythmias, hypotension, or respiratory 
depression. 
 
Contraindications 
• 
any use other than for the treatment of perioperative nausea and vomiting in patients for 
whom other treatments are ineffective or inappropriate  
• 
hypersensitivity to droperidol  
• 
QT interval prolongation (greater than 440 msec, males; greater than 450 msec, 
females), known or suspected, including patients with congenital long QT syndrome; 
serious or life-threatening arrhythmias may occur  
 
Precautions 
• 
QT prolongation, dose-dependent, and serious arrhythmias (eg, torsade de pointes, 
ventricular arrhythmias, cardiac arrest, and death) have been reported; risk factors 
include bradycardia (less than 50 beats/min), clinically significant cardiac disease, 
treatment with Class I and Class III antiarrhythmics, treatment with MAOIs, concomitant 
treatment with other drugs known to prolong the QT interval, and electrolyte imbalance 
(especially hypokalemia or hypomagnesemia) or concomitant treatment with drugs (eg, 
diuretics) that may cause electrolyte imbalance; monitoring recommended  
• 
anesthesia, conduction (eg, spinal and some peridural); altered respiration or circulation 
or hypotension may occur  
• 
concomitant use with potentially arrhythmogenic agents (eg, class I or III antiarrhythmics, 
antihistamines that prolong the QT interval, antimalarials, calcium channel blockers, 
neuroleptics that prolong the QT interval, and antidepressants); avoid use  
• 
elderly, debilitated, or poor-risk patients, dose adjustment recommended  
• 
electroencephalogram, patterns may be slow to return to normal  
• 
hepatic impairment; risk of drug toxicity  
• 
neuroleptic malignant syndrome (altered consciousness, muscle rigidity, and autonomic 
instability) has occurred rarely and may be difficult to differentiate from malignant 
hyperpyrexia; consider treating with dantrolene  
• 
pheochromocytoma, diagnosed or suspected, severe hypertension and tachycardia have 
been reported  
• 
pulmonary arterial pressure may decrease; use caution when interpreting results  
• 
renal impairment; kidney is important in metabolizing and excreting drugs 
 
 
ENALAPRIL MALEATE 
Brand Name(s): Vasotec 
Adverse Effects 
Serious:  
• 
Gastrointestinal: Intestinal angioedema 
• 
Hematologic: Agranulocytosis 
• 
Hepatic: Hepatotoxicity, Liver failure (rare) 
• 
Renal: Acute renal failure (0.5% to 1%), Renal impairment 
• 
Other: Angioedema (0.1% to 1%) 
 
Common: 

 
 
 
 
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• 
Cardiovascular: Hypotension (0.9% to 6.7%) 
• 
Endocrine metabolic: Hyperkalemia (1% to 3.8%) 
• 
Neurologic: Dizziness (4.3% to 7.9%) 
• 
Renal: Serum blood urea nitrogen raised (0.2% to 11%), Serum creatinine raised (0.2% 
to 11%) 
• 
Respiratory: Cough (1% to 15%) 
• 
Other: Fatigue (3%) 
 
Patient Information 
• 
Patient should avoid activities requiring coordination until drug effects are realized, as 
drug may cause dizziness. 
• 
Instruct patient to rise slowly from a sitting/supine position. 
• 
This drug may cause nausea, vomiting, or asthenia. 
• 
Instruct patient to report signs/symptoms of hypotension or persistent cough. 
• 
Tell patient to report signs/symptoms of angioedema (deep swelling around eyes and lips 
and sometimes hands and feet) or intestinal angioedema (abdominal pain). 
• 
Advise patient to maintain adequate hydration during therapy. 
• 
Patient should avoid use of potassium-sparing diuretics or potassium-containing 
supplements or salt substitutes, as this may cause increased potassium levels 
 
Contraindications 
• 
angioedema, hereditary or idiopathic  
• 
angioedema related to prior therapy with an ACE inhibitor (history of)  
• 
hypersensitivity to enalapril  or enalaprilat, an active metabolite of enalapril 
 
Precautions 
• 
pregnancy, second and third trimesters; can cause fetal and neonatal morbidity and 
death; discontinue enalapril therapy  
• 
anaphylaxis during lipid apheresis with dextran sulfate membranes and hemodialysis with 
high flux membranes has been reported  
• 
angioedema, head and neck; has occurred; discontinue therapy  
• 
angioedema (intestinal) has been reported; increased risk in patients with history of 
intestinal angioedema  
• 
aortic stenosis/hypertrophic cardiomyopathy, history of; vasodilation  
• 
cerebrovascular disease; history of; excessive hypotension may result in cerebrovascular 
accident  
• 
CHF, history of; risk for excessive hypotension sometimes associated with oliguria and/or 
progressive azotemia, and rarely with acute renal failure and/or death 
• 
concomitant diuretic therapy, high dose; risk for excessive hypotension sometimes 
associated with oliguria and/or progressive azotemia, and rarely with acute renal failure 
and/or death  
• 
hepatic failure has occurred; discontinue therapy in patients who develop jaundice or 
have marked elevations in hepatic enzymes  
• 
hyperkalemia has been reported; increased risk with renal disease, diabetes, and 
concomitant use of potassium supplements, potassium containing salt substitutes, and 
potassium-sparing diuretics  
• 
hyponatremia, presence of; risk for excessive hypotension sometimes associated with 
oliguria and/or progressive azotemia, and rarely with acute renal failure and/or death  

 
 
 
 
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• 
insect venom allergy, hymenoptera venom immunotherapy; may exacerbate the allergic 
response  
• 
ischemic heart disease, history of; excessive hypotension may result in myocardial 
infarction  
• 
renal dialysis therapy; risk for excessive hypotension sometimes associated with oliguria 
and/or progressive azotemia, and rarely with acute renal failure and/or death  
• 
renal impairment; risk for excessive hypotension sometimes associated with oliguria 
and/or progressive azotemia, and rarely with acute renal failure and/or death  
• 
renal impairment, especially in the presence of collagen vascular disease; 
agranulocytosis and neutropenia have occurred  
• 
surgery/anesthesia; excessive hypotension has been reported  
• 
volume and/or salt depletion (severe), presence of; risk for excessive hypotension 
sometimes associated with oliguria and/or progressive azotemia, and rarely with acute 
renal failure and/or death 
 
 
Epirubicin 
 
Common 
Serious 
Alopecia 
Rash 
Abnormal skin appearance  
Hot sweats 
Diarrhea 
Inflammatory disease of mucous membrane 
Nausea 
Vomiting  
Lethargy 
Amenorrhea 
Fever 
Infection 
Radiation recall syndrome 
Abnormal ECT 
Cardiotoxicity 
Possibly fatal CHF 
Tissue necrosis (skin, local) 
Hyperuricemia 
Tumor lysis syndrome 
Acute myeloid leukemia (secondary) 
Myelosupperssion (possibly severe) 
Anaphylaxis 
Immune hypersensitivity reaction 
• 
Advise patient to avoid vaccines during therapy due to drug-induced immunosuppression. 
• 
Warn patient that urine may have red-discoloration for 1 to 2 days after treatment. 
• 
Patients with prior radiation therapy may experience an inflammatory recall reaction 
(inflamed skin at the old radiation sites when a new chemotherapy drug is administered). 
• 
This drug may cause alopecia, hot flashes, diarrhea, inflamed mucous membranes, 
nausea, vomiting, lethargy, amenorrhea, or fever. 
• 
Instruct patient to report signs/symptoms of extravasation immediately, as drug is caustic. 
• 
Advise patient to report signs/symptoms of congestive heart failure, which may indicate 
cardiac toxicity. 
• 
Patient should report signs/symptoms of myelosuppression, hepatic dysfunction, or renal 
dysfunction. 
• 
Tell patient to maintain adequate hydration during drug therapy. 
 
 
 
 
 

 
 
 
 
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ERGOCALCIFEROL 
Brand Name(s): Drisdol 
Adverse Effects 
Serious:  
• 
Endocrine metabolic: Hypercalcemia, Hypervitaminosis D, Renal impairment, 
calcification of soft tissues, bone demineralization, growth retardation, nausea, 
constipation, mild acidosis, weight loss 
 
Common: 
 
• 
None indicated 
 
Patient Information 
• 
Patient should report signs/symptoms of hypercalcemia (nausea, vomiting, muscle 
weakness or tetany, increased thirst, confusion, abdominal pain). 
• 
Maintain adequate dietary intake of calcium as instructed by healthcare professional. 
• 
Patient should avoid additional supplemental sources of vitamin D, unless approved by 
healthcare professional. 
 
Contraindications 
• 
abnormal sensitivity to the toxic effects of vitamin D  
• 
hypercalcemia  
• 
hypervitaminosis D  
• 
malabsorption syndrome 
 
Precautions 
• 
adequate dietary calcium; necessary for clinical response to vitamin D therapy  
• 
evaluate vitamin D intake from fortified foods, dietary supplements, and self-administered 
and prescription drug sources  
• 
hyperphosphatemia may occur; must maintain normal serum phosphorus levels by 
aluminum gel administration and/or dietary phosphate restriction to prevent metastatic 
calcification  
• 
hypersensitivity to vitamin D, particularly in infants with idiopathic hypercalcemia  
• 
hypoparathyroidism; dihydrotachysterol, intravenous calcium, and/or parathyroid 
hormone may be required during treatment  
• 
tartrazine (FD&C Yellow No. 5) sensitivity; increased risk of allergic reactions including 
bronchial asthma in susceptible patients, especially in patients with concomitant aspirin 
sensitivity (Drisdol(R))  
• 
vitamin D-resistant rickets; the range between therapeutic and toxic doses is narrow 
 
 
 
Erlotinib (Tarceva/OSI-774) 
 
We know about the following side effects of OSI-774: 
 
Common 
(happens in 21-100 
patients out of 100) 
Occasional 
(happens in 5-20 
patients out of 100) 
Rare 
(happens in less than 5 patients out 
of 100) 
The timing of 
these side effects 
Acne-like skin rash, 
diarrhea, nausea, 
Dry skin, dry 
mouth, decreased 
Peeling of the skin, hives and itching, 
elevation in liver function tests, 

 
 
 
 
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(how soon they 
happen after 
taking OSI-774) is 
not known. 
vomiting, tiredness, 
weariness, ill feeling 
appetite, mouth 
sores, heartburn 
redness/inflammation of the 
eye/damage to the cornea, dry eye, 
inward growth of eyelashes, tearing, 
kidney damage, headache, 
inflammation of the lungs, lung 
tissue changes and damage and 
scarring of lung tissues, blurry 
vision, allergic reaction, changes to 
taste, increase in bilirubin 
Allergic reactions may occur with any medicine. 
 
Also reported on OSI-774 trials but with the relationship to OSI-774 unknown: low levels of 
red blood cells, low levels of white blood cells, increased numbers of white blood cells in the 
blood, low number of platelets in the blood which may increase the risk of bleeding, poor 
blood supply to an area of bone causing bone death, blockage of the pulmonary artery (1 
case), a clot blocking a vein, shaking chills, fever, hair loss, sore throat, burning or painful 
sensation in the tongue, inflammation and cracking of the skin of the lips, constipation, 
abdominal pain or cramping, sores in the stomach, too much gas produced in the intestines, 
difficulty swallowing, decreased blood flow to the intestines, inflammation of the pancreas, 
blood in the urine, nose bleed, dark, bloody bowel movement, blood in sputum or spit, 
bleeding in the intestines, elevated liver enzyme levels, inflammation of the lungs, urinary 
tract infection, infection with or without decrease in a type of white blood cell called a 
neutrophil, low levels of potassium and sodium in the blood, dryness in the nose, runny 
nose, depression, anxiety, sleeplessness, a skin sensation, such as burning, prickling, itching, 
or tingling, with no apparent cause, dizziness, blockage of the blood vessels of the brain (1 
case), back pain, cough, difficulty breathing, too much protein in the urine, kidney failure, 
inflammation of the lining of the uterus, confusion, dehydration and increased levels of urea 
in the blood which is likely directly related to diarrhea, changes in blood clotting in patients 
also taking Coumadin, inflammation of the cornea causing watery painful eyes and blurred 
vision, inflammation of the eye, inflammation of the pancreas, the presence of air or gas in 
abnormal places in the body, and secondary skin infection from rash. 
 
If a person gets pregnant while receiving OSI-774, it could be dangerous for the baby. You 
should not become pregnant or father a baby while on this study. You should not nurse 
(breast feed) a baby while on this study. Ask about counseling and more information about 
preventing pregnancy. Women of child-bearing potential and males must agree to use an 
adequate form of birth control while on this protocol. 
 
ERYTHROMYCIN 
Brand Name(s): Ak-mycin ; Akne-Mycin ; Eryc ; Erymax ; Erythrocin ; Robimycin ; Sansac ; 
Staticin ; T-Stat 
Adverse Effects 
Serious:  
• 
Cardiovascular: Cardiac dysrhythmia, Prolonged QT interval, Torsades de pointes, 
Ventricular tachycardia 
• 
Dermatologic: Stevens-Johnson syndrome, Toxic epidermal necrolysis due to drug 
• 
Gastrointestinal: Clostridium difficile colitis, Pancreatitis 
• 
Hepatic: Cholestatic hepatitis, Hepatitis 
• 
Immunologic: Anaphylaxis 
• 
Neurologic: Seizure 
• 
Otic: Ototoxicity 

 
 
 
 
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• 
Renal: Interstitial nephritis 
 
Common: 
• 
Gastrointestinal: Diarrhea, Loss of appetite, Nausea, Stomach cramps, Vomiting 
 
Patient Information 
• 
This drug may cause loss of appetite, nausea, stomach cramps, or vomiting. 
• 
Elderly patients are more susceptible to development of dysrhythmia and torsade de 
pointes. 
• 
Elderly patients with renal or hepatic dysfunction are at increased risk of ototoxicity. 
• 
Instruct patient to report severe diarrhea and consult healthcare professional prior to 
taking anti-diarrhea medicine. 
• 
Elderly patients on concomitant anticoagulant therapy should monitor for signs/symptoms 
of bleeding, as drug may have additive effects. 
• 
Patients with a history of myasthenia gravis should report signs/symptoms of disease 
exacerbation during therapy. 
• 
Patients using the topical gel should avoid contact with eyes and all mucous membranes. 
• 
Do not use with astemizole, cisapride, pimozide, terfenadine, or lovastatin 
 
Contraindications 
• 
concomitant therapy with astemizole, cisapride, dihydroergotamine, ergotamine, 
pimozide, or terfenadine  
• 
hypersensitivity to erythromycin or any component of the product 
 
Precautions 
• 
concomitant therapy with colchicine; colchicine toxicity has been reported; potential to be 
life-threatening and may occur at recommended doses  
• 
concomitant therapy with lovastatin; rhabdomyolysis, with or without renal impairment, 
has been reported in seriously ill patients; monitoring recommended  
• 
early syphilis in pregnancy; oral erythromycin may not prevent congenital syphilis; 
administer appropriate penicillin regimen to infant born to woman treated with oral 
erythromycin for early syphilis  
• 
elderly patients, especially with renal or hepatic dysfunction; increased risk of 
erythromycin-associated hearing loss  
• 
elderly patients; increased susceptibility to torsades de pointes arrhythmias  
• 
hepatotoxicity (eg, increased liver enzymes, and hepatocellular and/or cholestatic 
hepatitis, with or without jaundice) has been reported with use of oral erythromycin 
products  
• 
impaired hepatic function; erythromycin primarily excreted by the liver  
• 
infantile hypertrophic pyloric stenosis has been reported  
• 
myasthenia gravis, exacerbation or new onset, has occurred  
• 
superinfection; may occur as a result of overgrowth of nonsusceptible organisms; 
discontinue if superinfection occurs 
 
 
 
 
 
 

 
 
 
 
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Estradiol 
 
Common 
Serious 
Edema (transdermal system, 0.5% to 13%) 
Application site irritation (transdermal spray, 
1.3%; transdermal system, 5.7% to 56.7%) 
Chloasma 
Hirsutism 
Persistent erythema of skin (transdermal patch, 
17%) 
Pruritus (topical emulsion, 4%; topical gel, 4.8%) 
Weight change 
Bloating symptom 
Nausea 
Vomiting 
Migraine 
Depression (transderamal system, 1% to 8%) 
Mood disturbance  
Breast tenderness (topical gel, 2.5% to 8.8%; 
transdermal spray, 5% to 7%; transdermal system, 
6.5% to 17%) 
Menstruation disorder 
Leucorrhea 
Breast swelling 
Vaginal discomfort (vaginal cream, 5%; vaginal 
ring, 5%) 
Withdrawal bleeding 
Heart disease 
Hypertension 
Myocardial infarction 
Body fluid retention 
Breast cancer 
Diabetes mellitus 
Hypercalcemia 
Gallbladder disorder 
Venous thromboembolism 
Anaphylaxis 
Cerebrovascular accident 
Dementia 
Impaired cognition 
Thrombosis of retinal vein 
Malignant neoplasm of endometrium of corpus 
uteri 
Ovarian cancer 
Pulmonary embolism 
 
• 
This drug may cause edema, chloasma, change in weight, nausea, vomiting, headache, 
depression, amenorrhea, break-through bleeding, breast tenderness, swollen breast, breast 
cancer, or endometrial cancer. The vaginal insert formulation may also cause vaginal 
discomfort. 
• 
Instruct patient to report abnormal vaginal bleeding or signs/symptoms of a 
thromboembolic disorder. 
• 
Advise patients using the vaginal insert, tablet, or cream to report signs/symptoms of a 
vaginal infection. 
• 
Instruct patient on proper administration technique depending on form. 
• 
If the vaginal insert falls out after insertion, patient may rinse it in lukewarm water and 
reinsert. 
• 
Advise patient that the transdermal patch should never be placed on the breast or the 
waistline. At least 1 week should be allowed between applications to a particular site. 
• 
Patients should not smoke during therapy, as this increases the risk of thromboembolic 
events. 
• 
Advise patients using the topical emulsion to not use sunscreen over the application site, 
as this may increase the estrogen absorption. 
• 
Avoid eating grapefruit or drinking grapefruit juice while taking oral preparations this 
drug. 
 
 

 
 
 
 
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Ethacrynic acid 
 
Common 
Serious 
Injection site reaction (irritation, pain) 
Rash 
Abnormal electrolytes 
Diarrhea 
Dyphagia 
Loss of appetite 
Nausea 
Vomiting 
Gout 
Confusion  
Headache 
Vertigo 
Blurred vision 
Fatigue 
Pancreatitis (rare) 
Agranulocytosis 
Neutropenia 
Thrombocytopenia 
Hepatotoxicity (rare) 
Jaundice (rare) 
Ototoxicity 
Deafness 
Tinnitus 
Hematuria 
 
      
 
This drug may cause hyper- or hypoglycemia, abdominal pain, diarrhea, dysphagia, loss of 
appetite, nausea, vomiting, gout, confusion, headache, vertigo, blurred vision, fatigue, 
pancytopenia, or hematuria. 
 
Instruct patient to report severe, watery diarrhea or signs/symptoms of ototoxicity. 
 
Patient should avoid lithium during drug therapy. 
 
ETHAMBUTOL HYDROCHLORIDE 
Brand Name(s): Myambutol 
Adverse Effects 
Serious:  
• 
Hematologic: Neutropenia, Thrombocytopenia 
• 
Immunologic: Anaphylactoid reaction 
• 
Neurologic: Peripheral neuropathy 
• 
Ophthalmic: Blindness AND/OR vision impairment level, Optic neuritis (1-6%) 
 
Common: 
• 
Endocrine metabolic: Hyperuricemia 
• 
Gastrointestinal: Nausea and vomiting 
• 
Psychiatric: Mania 
 
Patient Information 
• 
This drug may cause nausea, vomiting, hyperuricemia, or mania. 
• 
Drug may cause vision impairment or loss. Instruct patient to promptly report any visual 
changes. 
• 
Patient should report signs/symptoms of neutropenia, thrombocytopenia, or peripheral 
neuropathy 
 
Contraindications 
• 
hypersensitivity to ethambutol hydrochloride  
• 
inability to appreciate and report visual side effects or changes in vision (eg, young 
children or unconscious patients)  

 
 
 
 
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• 
optic neuritis, unless clinical judgment determines that it may be used 
 
Precautions 
• 
blindness, irreversible, has been reported  
• 
concomitant use of antacids that contain aluminum hydroxide should be avoided for 4 
hours following administration  
• 
liver toxicities, including fatalities, have been reported; monitoring recommended  
• 
renal impairment; dose adjustment recommended  
• 
visual acuity has been reduced, possibly due to optic neuritis and related to dose and 
treatment duration  
• 
visual defects (eg, cataracts, recurrent inflammatory conditions of the eye, optic neuritis, 
and diabetic retinopathy); monitoring recommended  
 
 
 

 
 
 
 
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ETHIONAMIDE 
Brand Name(s): Trecator 
Adverse Effects 
Serious:  
• 
Hepatic: Hepatitis 
• 
Neurologic: Encephalopathy 
• 
Ophthalmic: Optic neuritis (rare .) 
• 
Psychiatric: Psychiatric sign or symptom 
 
Common: 
• 
Gastrointestinal: Abdominal pain, Diarrhea, Metallic taste, Nausea, Stomatitis, Vomiting 
 
Patient Information 
• 
Patient should avoid activities requiring mental alertness or coordination until drug effects 
are realized, as drug may cause drowsiness or dizziness. 
• 
This drug may cause gynecomastia, nausea, vomiting, diarrhea, metallic taste, postural 
hypotension, or impotence. 
• 
Patient should report visual changes or signs/symptoms of optic neuritis. 
• 
Advise diabetic patients to monitor for signs/symptoms of hypoglycemia and to report 
difficulties with glycemic control. 
• 
Patient should take drug with a meal to minimize gastric irritation. 
• 
Advise patient against excessive alcohol consumption during therapy. 
 
Contraindications 
• 
hypersensitivity to ethionamide or components 
• 
severe hepatic damage 
 
Precautions 
• 
drug malabsorption may be a problem in patients with concomittant AIDS infection 
• 
diabetes control may be disrupted by ethionamide 
• 
pregnancy 
 
 
ETHOSUXIMIDE 
Brand Name(s): Zarontin 
Adverse Effects 
Serious:  
• 
Dermatologic: Stevens-Johnson syndrome 
• 
Hematologic: Agranulocytosis, Aplastic anemia, Drug-induced eosinophilia, Leukopenia, 
Pancytopenia 
• 
Immunologic: Systemic lupus erythematosus 
• 
Neurologic: Seizure 
 
Common: 
• 
Gastrointestinal: Loss of appetite, Nausea, Stomach cramps, Vomiting 
• 
Neurologic: Ataxia, Dizziness, Headache, Somnolence 
• 
Other: Hiccoughs 
 

 
 
 
 
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Patient Information 
• 
Patient should avoid activities requiring mental alertness or coordination until drug effects 
are realized as drug may cause dizziness, drowsiness, and fatigue.  
• 
This drug may cause anorexia, nausea, stomach cramps, abdominal pain, diarrhea, 
vomiting, ataxia, and headaches.  
• 
Advise patient or caregiver to report worsening depression, suicidal ideation, or unusual 
changes in behavior.  
• 
Patient should report signs/symptoms of systemic lupus erythematosus (arthralgia, 
myalgia, fatigue, skin rash) or a severe skin reaction such as Stevens-Johnson syndrome 
(flu-like symptoms, spreading red rash, or skin/mucous membrane blistering).  
• 
Instruct patient to report signs/symptoms of blood dyscrasias (eg, sore throat, fever, 
malaise, bruising, petechiae, skin rash, or epistaxis) or hepatic dysfunction.  
• 
Advise patient against sudden discontinuation of drug, as this may precipitate petit mal 
seizures.  
 
Contraindications 
• 
hypersensitivity to succinimides 
 
Precautions 
• 
abrupt withdrawal should be avoided due to the potential for status epilepticus  
• 
blood dyscrasias, some fatal, have been reported; monitoring recommended  
• 
grand mal seizures may occur more frequently when used as monotherapy for mixed 
types of epilepsy  
• 
liver disease, preexisting; liver function abnormalities have been reported; monitoring 
recommended  
• 
pregnancy; may increase risk for birth defects in newborns; assess risk/benefit  
• 
renal disease, preexisting; renal function abnormalities have been reported; monitoring 
recommended  
• 
suicidality, increased risk of; monitoring recommended  
• 
systemic lupus erythematosus has been reported  
 
 
Etodolac 
 
Common 
Serious 
Edema 
Abdominal pain 
Diarrhea 
Flatulence 
Indigestion 
Nausea 
Dizziness 
Malaise 
Congestive heartfailure (<1%) 
Myocardial infarction 
Thrombotic tendency observations 
Scaling eczema 
Stevens-Johnson syndrome (<.0.1%) 
Toxic epidermal necrolysis (<0.1%) 
Gastrointestinal hemorrhage (<1%) 
Gastrointestinal perfoatin (<1%) 
Inflammatory disorder of digestive tract 
Melena (<3%) 
Agranulocytosis (rare) 
Anemia (<1%) 
Neutropenia (rare) 
Thrombocytopenia (<1%) 
Hepatitis (<1%) 

 
 
 
 
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Increased liver function test (up to 15%) 
Jaundice (<1%) 
Liver failure (<0.1%) 
Anaphylactoid reaction 
Immune hypersensitivity reaction (rare) 
Cerebrovascular accident 
Papillary necrosis (rare) 
Renal failure (rare) 
Bronchospasm (<2%) 
 
 
Avoid use in late pregnancy as drug may cause premature closure of ductus arteriosus. 
 
This drug may cause edema, abdominal pain, diarrhea, dyspepsia, flatulence, nausea, dizziness, 
or malaise. 
 
Instruct patients to report signs/symptoms of serious gastrointestinal adverse events such as 
bleeding, ulceration, perforation of stomach or intestines. Elderly and debilitated patients are at 
a higher risk for these effects. 
 
Patients should report signs/symptoms of serious cardiovascular thrombotic events, such as 
myocardial infarction and stroke. Patients with a cardiovascular disease history or on 
prolonged therapy are at a higher risk of these events. 
 
May be taken with food or milk to minimize stomach upset. 
 
Patient should avoid all other NSAIDs during therapy, unless approved by a healthcare 
professional. 
 
Patient should not drink alcohol while taking this drug. 
 
 
 
 
 
 
 
 
Etoposide (Vepesid) 
 
 
Common 
Happens to 21-100 children out 
of every 100 
Occasional 
Happens to 5-20 children 
out of every 100 
Rare 
Happens to <5 children out of 
every 100 
Immediate: 
Within 1-2 days 
of receiving drug 
Nausea, vomiting 
Decreased or loss of 
appetite, drop in blood 
pressure while receiving 
this drug 
Allergic reaction 
Prompt: 
Within 2-3 
weeks, prior to 
next course 
Decrease in the number of red 
and white blood cells and 
platelets made in the bone 
marrow 
Hair loss (L), worsens 
side effects due to 
radiation treatments, 
diarrhea 
Numbness, tingling, 
clumsiness, mouth sores, 
damage to the liver 
Delayed: 
Any time later 
during therapy 
 
 
 
Late: 
Any time after 
completion of 
 
 
A new cancer or leukemia 
resulting from this treatment, 
inability of the ovaries to 

 
 
 
 
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treatment 
produce eggs and/or hormones 
resulting in inability to have 
children and/or hormonal 
problems 
(L) Toxicity may also occur later. 
 
 
Everolimus 
 
Adverse Effects 
Serious:  
• 
Hematologic: Decreased hemoglobin, Grade 4 (advanced renal cancer, 1% ; advanced 
pancreatic neuroendocrine tumor, 15%), Decreased lymphocyte count, Grade 4 
(advanced renal cancer, 2% ; advanced pancreatic neuroendocrine tumor, 16%), 
Hemorrhage (3%), Leukopenia (kidney transplant recipients, 3% ; subependymal giant 
cell astrocytoma, 54% ; advanced pancreatic neuroendocrine tumor, 43%), Thrombosis, 
Thrombotic microangiopathy, Thrombotic thrombocytopenic purpura 
• 
Immunologic: Infectious disease (advanced renal cancer, 37% ; kidney transplant 
recipients, 62%) 
• 
Neurologic: Seizure (29%) 
• 
Renal: Hemolytic uremic syndrome, Renal failure (3%), Thrombosis of renal artery (1% 
to less than 10%) 
• 
Respiratory: Non-infectious pneumonia (14% to 17%), Pleural effusion (7%), 
Pneumonia, Pulmonary embolism 
 
Common: 
• 
Cardiovascular: Hypertension (kidney transplant recipients, 30% ; advanced renal 
cancer, 4%; subependymal giant cell astrocytoma, 4%), Peripheral edema (kidney 
transplant recipients, 45% ; advanced renal cancer, 25%; subependymal giant cell 
astrocytoma, 4%) 
• 
Dermatologic: Infection of skin AND/OR subcutaneous tissue (18%), Rash (advanced 
renal cancer, 29%; subependymal giant cell astrocytoma, 18%; advanced pancreatic 
neuroendocrine tumor, 59%) 
• 
Endocrine metabolic: Decreased phosphate level (37% to 40%), Dyslipidemia (15%), 
Hyperlipidemia (21%), Increased glucose level, All grades (advanced pancreatic 
neuroendocrine tumor, 75%; advanced renal cell cancer, 57%; subependymal giant cell 
astrocytoma, 25%), Serum cholesterol raised (advanced renal cancer, 77%; 
subependymal giant cell astrocytoma, 68% ; advanced pancreatic neuroendocrine tumor, 
66%), Serum triglycerides raised (advanced renal cell cancer, 73%; subependymal giant 
cell astrocytoma, 43% ; advanced pancreatic neuroendocrine tumor, 39%) 
• 
Gastrointestinal: Constipation (kidney transplant recipients, 38% ; subependymal giant 
cell astrocytoma, 11%), Diarrhea (kidney transplant recipients, 19% ; advanced renal 
cancer, 30%; subependymal giant cell astrocytoma, 25%; advanced pancreatic 
neuroendocrine tumor, 50%), Loss of appetite (25% to 30%), Nausea (26% to 29%), 
Oropharyngeal mucositis, Stomatitis (kidney transplant recipients, 8% ; advanced renal 
cancer, 44%; advanced pancreatic neuroendocrine tumor, 70%; subependymal giant cell 

 
 
 
 
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astrocytoma, 86%), Ulcer of mouth, Vomiting (advanced renal cancer, 20%; 
subependymal giant cell astrocytoma, 21%; advanced pancreatic neuroendocrine tumor, 
29% ; kidney transplant recipients, 15%) 
• 
Hematologic: Anemia (kidney transplant recipients, 26% ; renal cell cancer, 50% or 
higher), Decreased hemoglobin, All grades (advanced renal cancer, 92%; subependymal 
giant cell astrocytoma, 39% ; advanced pancreatic neuroendocrine tumor, 86%), 
Decreased lymphocyte count, All grades (45% to 51%), Decreased platelet count, All 
grades (21% to 45%) 
• 
Hepatic: ALT/SGPT level raised (advanced renal cell cancer, 21%; subependymal giant 
cell astrocytoma, 46%; advanced pancreatic neuroendocrine tumor, 48%), AST/SGOT 
level raised (advanced renal cancer, 25%; advanced pancreatic neuroendocrine tumor, 
56%; subependymal giant cell astrocytoma, 89%) 
• 
Immunologic: Surgical wound finding (35%) 
• 
Neurologic: Asthenia (33%) 
• 
Otic: Otitis media (36%) 
• 
Renal: Serum creatinine raised (advanced renal cancer, 50%; advanced pancreatic 
neuroendocrine tumor, 19%; subependymal giant cell astrocytoma, 11% ; kidney 
transplant recipients, 18%), Urinary tract infectious disease (advanced pancreatic 
neuroendocrine tumor, 16% ; kidney transplant recipients, 22%) 
• 
Respiratory: Cough (advanced renal cancer, 30%; advanced pancreatic neuroendocrine 
tumor, 25%; subependymal giant cell astrocytoma, 21% ; kidney transplant recipients, 
7%), Dyspnea (20% to 24%), Sinusitis (39%), Upper respiratory infection (kidney 
transplant recipients, 16% ; subependymal giant cell astrocytoma, 82%) 
Other: Fatigue (advanced pancreatic neuroendocrine tumor, 45% advanced renal cancer, 31%; 
subependymal giant cell astrocytoma, 7% kidney transplant recipients, 9%), Fever (advanced 
renal cancer, 20%; advanced pancreatic neuroendocrine tumor, 31%; subependymal giant cell 
astrocytoma, 32% ; kidney transplant recipients, 19%) 
 
FAMOTIDINE 
Brand Name(s): Fluxid ; Pepcid 
Adverse Effects 
Serious:  
• 
Dermatologic: Stevens-Johnson syndrome (very rare), Toxic epidermal necrolysis (very 
rare) 
• 
Gastrointestinal: Necrotizing enterocolitis in fetus OR newborn 
• 
Immunologic: Anaphylaxis (infrequent), Angioedema (infrequent) 
• 
Neurologic: Seizure (rare) 
• 
Respiratory: Interstitial pneumonia (infrequent), Nosocomial pneumonia 
 
Common: 
• 
Gastrointestinal: Constipation (1.2% to 1.4%), Diarrhea (1.7%) 
• 
Neurologic: Dizziness (1.3%), Headache (1.3% to 4.7%) 
 
Patient Information 
• 
This drug may cause constipation, diarrhea, or dizziness. 
• 
Advise patient to take at bedtime. 
• 
Patient may take with antacids, if needed. 
 

 
 
 
 
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Contraindications 
• 
hypersensitivity to famotidine or any component  
• 
hypersensitivity to other H2-receptor antagonists, history  
 
Precautions 
• 
neonates, very low birth weight (401 to 1,500 g); increased risk of developing necrotizing 
enterocolitis  
• 
renal insufficiency, moderate or severe; risk of prolonged QT interval  and CNS adverse 
effects; dose adjustment recommended  
• 
symptomatic response does not rule out gastric malignancy  
 
 
Felbamate 
 
Common 
Serious 
Photosensitivity 
Weight loss 
 Abdominal pain 
Constipation  
Indigestion 
Loss of appetite 
Nausea 
Taste sense altered 
Vomiting 
Purpuric disorder 
Adnormal gait 
Dizziness 
Headache 
Insomnia 
Fever 
Stevens-Johnson syndrome 
Agrnulocytosis 
Aplastic anemia 
Bone marrow depression  
Drug-induced eosinophilia 
Leukopenia 
Pancytopenia 
Thrombocytopenia 
Hepatic failure (acute) 
Anaphylactoid reaction  
Seizure  
      
 
Patient should avoid activities requiring mental alertness or coordination until drug effects are 
realized. 
 
This drug may cause weight loss, abdominal pain, constipation, dyspepsia, loss of appetite, 
nausea, altered sense of taste, vomiting, purpuric disorder, abnormal gait, dizziness, headache, 
or insomnia. 
 
Instruct patient to report signs/symptoms of pancytopenia, hepatic failure, or Stevens-Johnson 
syndrome (flu-like symptoms, spreading red rash, or skin/mucous membrane blistering). 
 
Advise patient against sudden discontinuation of drug. 
 
Instruct patient to call healthcare provider for instructions if 2 or more doses are missed. 
 
Felodipine 
 
Common 
Serious 
Peripheral edema (2% to 17.4%) 
Flushing (1.6%) 
Drug-induced gingival hyperplasia (<0.5%) 
Dizziness (4.4%) 
Headache (10.3%) 
Angina (<0.5%) 
Hypotension (rare) 
Myocardial infarction (<0.5%) 
Tachyarrhythmia (0.4% to 2.5%) 

 
 
 
 
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 
Patient should avoid activities requiring coordination until drug effects are realized, as drug 
may cause dizziness. 
 
Warn patient that hypotension may occur, especially with the first dose and dosage changes. 
 
This drug may cause peripheral edema, flushing, headache, myocardial infarction, or 
tachyarrhythmia. 
 
Inform patient that mild gingival hyperplasia may occur. Incidence and severity can be 
minimized with good dental hygiene. 
 
Patient should report exacerbation in angina. This may occur more frequently with initial dose, 
dose changes, or during drug withdrawal. 
 
Patient may take drug without food or with a light meal. 
 
Advise patient against sudden discontinuation of drug. 
 
Patient should avoid eating grapefruit or drinking grapefruit juice while taking this drug. 
 
Patient should not drink alcohol while taking this drug. 
 
Fenoprofen 
 
Common 
Serious 
Edema 
Anemia 
Increased liver function test (up to 15%) 
 
Hypertension 
Myocardial infarction (<2%) 
Thrombotic tendency observations 
Scaling eczema 
Stevens-Johnson syndrome (<0.1%) 
Gastrointestinal perforation (<2%) 
Inflammatory disorder of digestive tract 
Hepatitis (<2%) 
Jaundice 
Liver failure(<0.1%) 
Anajphylactoid reaction 
Cerebrovascular accident 
Acute renal failure 
Bronchospasm (<2%) 
 
This drug may cause edema. 
 
Tell patient to report signs/symptoms of liver dysfunction or anemia. 
 
Patients with a history of cardiac disease or on long-term therapy may be at an increased risk 
for adverse cardiovascular thrombotic events. Advise patient to report signs/symptoms of 
myocardial infarction or stroke. 
 
Instruct patients to report signs/symptoms of serious gastrointestinal events such as bleeding, 
ulceration, or perforation of stomach or intestines. Elderly and debilitated patients may be at an 
increased risk for this adverse effect. 
 
Patient may take drug with meals or milk to lessen or prevent gastric upset. 
 
Fexofenadine 
 
Common 
rare 

 
 
 
 
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Nausea (1.6%) 
Dyspepsia (1.3%) 
Headache (31.2%) 
Drowsiness (1.3%) 
Fatigue (1.3%) 
Dizziness 
Otitis media 
Dysmenorrhea (1.5%) 
Decreased bilirubin 
Flu-like symptoms 
Upper respiratory infection 
 
Patient should avoid activities requiring mental alertness or coordination until drug effects are 
realized. 
 
This drug may cause dyspepsia, dizziness, headache, somnolence, dysmenorrhea, or fatigue. 
 
Take drug with water. Do not take with fruit juices (grapefruit, orange, apple). 
 
Patient should avoid administration of aluminum- or magnesium-containing antacids within 30 
min before or after taking drug. 
 
FLUCYTOSINE 
Brand Name(s): Ancobon 
Adverse Effects 
Serious:  
• 
Cardiovascular: Cardiotoxicity 
• 
Hematologic: Leukopenia, Myelosuppression, Thrombocytopenia 
• 
Renal: Renal failure 
 
Common: 
• 
Gastrointestinal: Abdominal pain, Diarrhea, Nausea, Vomiting 
• 
Neurologic: Confusion, Headache 
• 
Psychiatric: Hallucinations 
 
Patient Information 
• 
Patient should avoid activities requiring mental alertness or coordination until drug effects 
are realized. 
• 
This drug may cause diarrhea, nausea, vomiting, confusion, headache, somnolence, or 
hallucinations. 
• 
Instruct patient to report signs/symptoms of infection or bleeding. 
• 
Patient may administer a few capsules at a time over 15 min to minimize nausea and 
vomiting. 
 
Contraindications 
• 
hypersensitivity to flucytosine 
 
Precautions 
• 
bone marrow depression 
• 
renal impairment 
 
 
 
 
 
 

 
 
 
 
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FLUDARABINE PHOSPHATE 
Brand Name(s): Fludara ;  Oforta 
Adverse Effects 
Serious:  
• 
Hematologic: Decreased hemoglobin (14% to 60%), Hemolytic anemia, Neutropenia 
(37% to 59%), Pancytopenia, Thrombocytopenia (17% to 55%) 
• 
Neurologic: Neurotoxicity, Progressive multifocal leukoencephalopathy 
• 
Respiratory: Pulmonary toxicity 
• 
Other: Graft versus host disease, Tumor lysis syndrome (0.33% to 1%) 
 
Common: 
• 
Gastrointestinal: Loss of appetite (0% to 34%), Nausea (1% to 5%), Vomiting 
• 
Neurologic: Asthenia (9% to 65%), Paresthesia (4% to 12%) 
• 
Respiratory: Cough (6% to 44%) 
• 
Other: Fatigue (10% to 38%), Fever (11% to 69%), Infectious disease (12% to 44% .), 
Pain (5% to 22%), Shivering (11% to 19%) 
 
Patient Information 
• 
Instruct patient to avoid driving and other activities requiring mental alertness or 
coordination until drug effects are realized, as drug causes fatigue, weakness, visual 
disturbances, confusion, agitation, and seizures (rare).  
• 
Advise patient to avoid live vaccines during therapy due to drug-induced 
immunosuppression.  
• 
Counsel patient to avoid pregnancy during and for at least 6 months after completion of 
therapy.  
• 
Drug may cause chills, loss of appetite, nausea, vomiting, diarrhea, cough, malaise, 
pneumonia, or fever.  
• 
Instruct patient to report signs/symptoms of myelosuppression, neurotoxicity, or 
infections.  
• 
Tell patient not to crush oral tablets and to avoid direct contact with skin and mucous 
membranes or inhalation.  
• 
Fludarabine (Intravenous route, Powder for Solution, Solution) 
• 
Fludarabine (Oral route, Tablet) 
 
Contraindications 
• 
hypersensitivity to fludarabine or to any product ingredient  
 
Precautions 
• 
autoimmune hemolytic anemia (fatal) has occurred; monitor for hemolysis; discontinue if 
hemolysis occurs  
• 
autoimmune thrombocytopenia/thrombocytopenic purpura (ITP), Evan's syndrome, and 
acquired hemophilia has occurred; monitor for hemolysis (intravenous); discontinue if 
hemolysis occurs  
• 
neurotoxicity, severe; dose-dependent , delay or discontinue treatment if neurotoxicity 
occurs  
• 
concomitant pentostatin; use not recommended  
• 
bone marrow suppression, severe (anemia, thrombocytopenia and neutropenia), 
preexisting exacerbation or new onset; monitor blood counts before and during treatment  
• 
infection (fatal), has occurred, monitor for signs and symptoms of infection  
• 
impaired performance; risk of compromising ability to drive or operate machinery  

 
 
 
 
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• 
pregnancy, avoid during treatment and for 6 months after cessation of treatment due to 
the potential for fetal harm (fertile male patients must take contraceptive measures)  
• 
mild to moderate renal impairment, creatinine clearance 30 to 70 mL/min/1.73 m(2) or 
less; dose reduction and monitoring required  
• 
severe renal impairment, creatinine clearance less than 30 mL/min/1.73 m(2); use not 
recommended (intravenous); dose reduction and monitoring required (oral) 
• 
transfusion-associated graft-versus-host disease, has occurred after transfusion with 
non-irrradiated blood; recommend use of irradiated blood products  
• 
tumor lysis syndrome (may present as flank pain and hematuria); increased risk in 
patients with chronic lymphocytic leukemia (CLL) with large tumor burdens 
• 
vaccination with live vaccines, during and after treatment, should be avoided  
• 
adverse event reporting; Antisoma 1-866-949-7420 or Food and drug Administration 1-
800-FDA-1088, or www.fda.gov/medwatch (oral)  
 
 
 
 
Fludrocortisones 
 
Common 
Serious 
Edema 
Bruising symptom 
Impaired would healing 
Petechiae 
Rash 
Urticaria 
Decreased body growth (children) 
Abnormal electrolytes 
Hypokalemia 
Hyperglycemia 
Abdominal distension 
Peptic ulcer disease 
Drug-induced myopath 
Muscle weakness 
Headache 
Vertigo 
Glycosuria 
Irregular periods 
Cardiomegaly 
Congestive heart failure 
Hypertension 
Thrombophlebitis 
Secondary hypocortisolism 
Raised intracranial pressure 
seizure 
 
Advise patient to avoid vaccines during therapy unless approved by healthcare professional. 
 
Instruct patient to avoid exposure to chickenpox or measles. If exposure occurs, patient should 
notify healthcare professional. 
 
This drug may cause edema, bruising, impaired wound healing, petechiae, decreased body 
growth in children, abdominal distension, myopathy, muscle weakness, headache, vertigo, or 
irregular periods. 
 
Patient should report seizure activity or signs/symptoms of congestive heart failure. 
 
Advise patient against sudden discontinuation of drug. 
 
 
 
 

 
 
 
 
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FLUOXETINE HYDROCHLORIDE 
Brand Name(s): Prozac ; Sarafem ; Symbyax 
Adverse Effects 
Serious:  
• 
Cardiovascular: Prolonged QT interval 
• 
Endocrine metabolic: Hyponatremia 
• 
Hematologic: Bleeding (up to 1%) 
• 
Neurologic: Seizure 
• 
Psychiatric: Depression, worsening (rare), Mania (rare), Suicidal thoughts, Suicide 
• 
Other: Serotonin syndrome 
 
Common: 
• 
Dermatologic: Diaphoresis, Rash (7%) 
• 
Gastrointestinal: Loss of appetite (3.5% to 15%), Nausea (20% to 30% .), Xerostomia 
• 
Neurologic: Asthenia (9% to 21%), Dizziness (2% to 11%), Insomnia (9% to 26%), 
Somnolence (13%), Tremor (12%) 
• 
Psychiatric: Anxiety (3% to 9%), Feeling nervous (3% to 14%) 
• 
Respiratory: Pharyngitis (6% to 10%), Rhinitis (16% to 23%) 
 
Patient Information 
• 
Instruct patient to report use of a MAO inhibitor within the last 14 days prior to starting 
therapy. Notify patient that at least 5 weeks should be allowed between discontinuation of 
fluoxetine and initiation of MAO inhibitor therapy. 
• 
Patient should avoid activities requiring mental alertness or coordination until drug effects 
are realized. 
• 
This drug may cause anticholinergic effects, sweating, weight loss, dyspepsia, loss of 
appetite, nausea, asthenia, insomnia, tremor, abnormal ejaculation, or impotence. 
• 
Advise patient that symptomatic improvement may not be seen for a few weeks. 
• 
Instruct patient to report worsening depression, suicidal ideation, or unusual changes in 
behavior, especially at initiation of therapy or with dose changes. Children and 
adolescents are at higher risk for these effects during the first few months of therapy. 
• 
Advise patient to report abnormal bleeding. 
• 
Patient should report skin rash with or without systemic symptoms (fever, edema, 
pulmonary effects), as drug may cause serious cutaneous systemic illness. 
• 
Instruct diabetic patients to monitor for signs/symptoms of hyper- or hypoglycemia and 
report any changes in glycemic control. 
• 
Advise patient against sudden discontinuation of drug. 
• 
Advise patient not to use thioridazine with fluoxetine or within 5 weeks of discontinuation. 
Pimozide should not be used with fluoxetine. 
• 
Avoid NSAID or aspirin use during therapy. 
• 
Patient should not drink alcohol while taking this drug. 
• 
Instruct patients on a weekly dose to take a missed dose as soon as possible. Patient 
should then go back to regular schedule for the next week. 
Contraindications 
• 
concomitant use of monoamine oxidase inhibitors (MAOIs), pimozide, or thioridazine  
• 
hypersensitivity to fluoxetine or any components of the product  
• 
use of thioridazine or MAOIs within 5 weeks after fluoxetine discontinuation  
• 
use of fluoxetine within 14 days of MAOI discontinuation  

 
 
 
 
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Precautions 
• 
suicidal ideation and behavior or worsening depression; increased risk, particularly in 
children, adolescents, and young adults with major depressive and other psychiatric 
disorders during the first few months of therapy or following changes in dosage  
• 
abrupt withdrawal; serious discontinuation symptoms have been reported; gradual 
reduction in dose recommended  
• 
acute narrow angle glaucoma or increased intraocular pressure; mydriasis has been 
reported  
• 
allergic reactions, including anaphylaxis, angioedema, and urticaria have been reported; 
in the case of rash, or other possibly allergic symptoms for which an alternative etiology 
cannot be identified, discontinue therapy  
• 
bipolar disorder; increased risk of precipitation of a mixed/manic episode with 
antidepressant treatment only  
• 
concomitant use of NSAIDs, aspirin, warfarin, or other drugs that affect coagulation; 
abnormal bleeding, particularly the gastrointestinal tract, may occur; monitoring 
recommended  
• 
concomitant serotonergic drug use (serotonin precursors (tryptophan), SSRIs, serotonin-
norepinephrine reuptake inhibitors); risk of serotonin syndrome, use is not recommended 
• 
diabetes, history of; increased risk of hypoglycemia  
• 
pulmonary events, including fibrosis, have been rarely reported  
• 
seizures, history of  
• 
serotonin syndrome and neuroleptic malignant syndrome-like reactions (serotonin 
syndrome in its most severe form), have been reported with fluoxetine therapy alone or in 
combination with other serotonergic drugs; monitoring recommended  
• 
skin reactions, including serious cutaneous systemic illnesses (eg leukocytoclastic 
vasculitis, erythema multiforme, and lupus-like syndrome) with fatalities have been 
reported rarely; in the case of rash, or other possibly allergic symptoms for which an 
alternative etiology cannot be identified, discontinue therapy 
• 
volume-depleted, elderly, or concurrent diuretic therapy; hyponatremia and syndrome of 
inappropriate antidiuretic hormone secretion (SIADH) has occurred with fluoxetine  
 
 
Fluvastatin 
 
Common 
Serious 
Abdominal pain (3.7% to 4.9%)  
Diarrhea (3.3% to 7.9%) 
Nausea (2.5% to 3.2%) 
Headache 
Pancreatitis (rare) 
Increased liver enzymes (1.1%) 
Disorder of muscle 
Rhabdomyolysis (rare) 
Tendon rupture 
 
This drug may cause abdominal pain, diarrhea, dyspepsia, nausea, or headache. 
 
Instruct patient to report signs/symptoms of renal failure or myopathy. 
 
Advise patients to administer capsule at least 2 h after taking a bile-acid resin (cholestyramine) 
if using concomitantly. 
 
Patient should not drink alcohol while taking this drug. 
 
Patient should avoid concomitant use of fibrates, niacin, cyclosporine, macrolides, or azole 
antifungals (eg, fluconazole, itraconazole), as combination may increase risk of myopathy. 
 
 

 
 
 
 
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FLUVOXAMINE MALEATE 
Brand Name(s): Luvox 
Adverse Effects 
Serious:  
• 
Dermatologic: Stevens-Johnson syndrome, Toxic epidermal necrolysis 
• 
Endocrine metabolic: Hyponatremia 
• 
Hematologic: Agranulocytosis, Bleeding, Abnormal 
• 
Immunologic: Anaphylaxis 
• 
Neurologic: Seizure (0.2%) 
• 
Psychiatric: Depression, worsening, Suicidal thoughts, Suicide 
• 
Other: Neuroleptic malignant syndrome, Serotonin syndrome 
 
Common: 
• 
Dermatologic: Sweating (immediate-release, 7%; extended-release, 7%) 
• 
Gastrointestinal: Diarrhea (immediate-release, 11%; extended-release, 18%), 
Indigestion (immediate-release, 10%; extended-release, 8%), Loss of appetite 
(immediate-release, 6%; extended-release, 13%), Nausea (immediate-release, 40%; 
extended-release, 34%), Xerostomia (immediate-release, 14%; extended-release, 10%) 
• 
Neurologic: Asthenia (immediate-release, 14%; extended-release, 26%), Dizziness 
(immediate-release, 11%; extended-release, 12%), Insomnia (immediate-release, 21%; 
extended-release, 35%), Somnolence (immediate-release, 22%; extended-release, 27%), 
Tremor (immediate-release, 5%; extended-release, 6%) 
• 
Psychiatric: Anxiety (immediate-release, 5%; extended-release, 6%), Feeling nervous 
(immediate-release, 12%) 
• 
Reproductive: Abnormal ejaculation (immediate-release, 8%; extended-release, 10%), 
Orgasm incapacity (immediate-release, 2%; extended-release, 5%) 
 
Patient Information 
• 
Instruct patient to report use of a MAO inhibitor within the last 14 days prior to initiation of 
drug therapy. 
• 
Patient should avoid activities requiring mental alertness or coordination until drug effects 
are realized, as drug may cause dizziness or somnolence. 
• 
This drug may cause anticholinergic effects, weight loss, diarrhea, dyspepsia, nausea, 
vomiting, asthenia, headache, insomnia, agitation, anxiety, nervousness, or abnormal 
ejaculation. 
• 
Instruct patient to report worsening depression, suicidal ideation, or unusual changes in 
behavior, especially at initiation of therapy or with dose changes. Children and 
adolescents are at higher risk for these effects during the first few months of therapy. 
• 
Advise patient against sudden discontinuation of drug. 
• 
Advise patient there are multiple significant drug-drug interactions for this drug. Consult 
healthcare professional prior to new drug use (including over-the-counter and herbal 
drugs). 
• 
Patient should not drink alcohol while taking this drug. 
 
 
 
Contraindications 
• 
concomitant use with alosetron, pimozide, thioridazine, tizanidine , or ramelteon  
• 
concomitant use of an MAOI or within 14 days (before or after) fluvoxamine therapy  
 

 
 
 
 
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Precautions 
• 
suicidal ideation and behavior or worsening depression has been reported, particularly in 
children, adolescents, and young adults during the first few months of therapy or 
following changes in dosage; monitoring recommended  
• 
abnormal bleeding, including potentially life-threatening hemorrhages; has been reported  
• 
abrupt withdrawal; increased risk of serious discontinuation symptoms; monitoring and 
gradual dose reduction recommended  
• 
bipolar disorder; increased risk of precipitation of a mixed/manic episode with 
antidepressant monotherapy; rule out disorder prior to initiating therapy  
• 
concomitant use with alcohol should be avoided  
• 
concomitant use with serotonergic drugs (eg, SSRIs, serotonin-norepinephrine reuptake 
inhibitors), diazepam, or serotonin precursors (eg, tryptophan) is not recommended  
• 
hepatic impairment; decreased fluvoxamine clearance; lower initial doses and monitoring 
recommended  
• 
hyponatremia, primarily due to SIADH, has been reported, including serious cases 
(serum sodium less than 110 mmol/L); increased risk in elderly, volume-depleted 
patients, or with concomitant use of diuretics; discontinue if symptomatic hyponatremia 
occurs  
• 
mania, history of; risk of activation of mania/hypomania  
• 
seizure disorder, history of; seizures have been reported; avoid use in unstable epilepsy; 
monitoring recommended if controlled epilepsy  
• 
serotonin syndrome has been reported, including cases that are life-threatening or that 
resemble neuroleptic malignant syndrome; monitoring recommended 
• 
report suspected adverse reactions to the US Food and Drug Administration at 1-800-
FDA-1088 or www.fda.gov/Medwatch  
 
FOLIC ACID 
Brand Name(s): Folacin-800 
Adverse Effects 
Serious:  
• 
Immunologic: Allergy 
 
Common: 
• 
Gastrointestinal: Bad taste in mouth, Large doses, Loss of appetite, Nausea 
• 
Neurologic: Confusion 
• 
Psychiatric: Irritability, Sleep pattern disturbance 
 
Patient Information 
• 
his drug may cause loss of appetite, nausea, confusion, irritability, or sleep-pattern 
disturbance. Large doses of drug may cause bad taste in mouth. 
• 
Patient should not drink alcohol while taking this drug. 
 
Contraindications 
• 
hypersensitivity to folic acid products 
 
Precautions 
• 
folic acid doses above 0.1 mg/day may obscure pernicious anemia (hematologic 
remission while neurological manifestations progress) 
• 
pernicious anemia and other megaloblastic anemias caused by vitamin B12 deficiency 

 
 
 
 
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FUROSEMIDE 
Brand Name(s): Lasix 
Adverse Effects 
Serious:  
• 
Cardiovascular: Orthostatic hypotension 
• 
Dermatologic: Erythema multiforme, Erythroderma, Stevens-Johnson syndrome, Toxic 
epidermal necrolysis due to drug 
• 
Gastrointestinal: Pancreatitis 
• 
Hematologic: Agranulocytosis, Aplastic anemia, Thrombocytopenia 
• 
Immunologic: Anaphylaxis 
 
Common: 
• 
Endocrine metabolic: Hyperuricemia (40%), Hypomagnesemia 
• 
Gastrointestinal: Loss of appetite 
• 
Renal: Spasm of bladder 
 
Patient Information 
• 
Drug causes sun-sensitivity. Advise patient to use sunscreen and avoid tanning beds. 
• 
Patient should avoid activities requiring coordination until drug effects are realized, as 
drug may cause dizziness, vertigo, or blurred vision. 
• 
This drug may cause hyperglycemia, hyperuricemia, constipation, diarrhea, loss of 
appetite, nausea, vomiting, purpuric disorder, cramps, spasticity, asthenia, headache, 
paresthesia, or scaling eczema. 
• 
Instruct patient to report unusual bleeding/bruising or signs/symptoms of hypotension, 
infection, pancreatitis, or ototoxicity (tinnitus, hearing impairment). 
• 
Advise patient to report signs/symptoms of severe skin reactions (flu-like symptoms, 
spreading red rash, or skin/mucous membrane blistering) or erythema multiforme. 
• 
Instruct patient to eat high-potassium foods during drug therapy, as directed by 
healthcare professional. 
• 
Patient should not drink alcohol while taking this drug 
 
Contraindications 
• 
anuria  
• 
history of hypersensitivity to furosemide  
 
Precautions 
• 
diuresis, profound; may cause water and electrolyte depletion, dehydration, and blood 
volume reduction; monitoring recommended  
• 
blood dyscrasias may occur; monitoring recommended  
• 
blood glucose increases, alterations in glucose tolerance tests, or precipitation of 
diabetes have been reported  
• 
concomitant use of aminoglycosides should be avoided  
• 
concomitant use of ethacrynic acid not recommended  
• 
elderly patients; increased risk of dehydration  
• 
electrolyte depletion, preexisting; should be corrected prior to treatment  
• 
electrolyte imbalance (eg, hyponatremia, hypochloremic alkalosis, hypokalemia, 
hypomagnesemia, hypocalcemia) may occur, especially in patients receiving higher 
doses and a restricted salt intake; monitoring recommended  

 
 
 
 
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• 
hepatic cirrhosis and ascites, preexisting; may precipitate hepatic coma with sudden fluid 
or electrolyte alteration; monitoring recommended  
• 
hepatic coma, preexisting; use not recommended until basic condition improved  
• 
hepatic damage may occur; monitoring recommended allergy to sulfonamides; may also 
be allergic to furosemide  
• 
hyperuricemia, asymptomatic or gout; may occur  
• 
hypokalemia has been reported; especially with brisk diuresis, inadequate electrolyte 
intake, cirrhosis, or concomitant use with corticosteroids, ACTH, large amounts of 
licorice, or prolonged use of laxatives  
• 
hypoproteinemia; reduced efficacy and increased risk of ototoxicity  
• 
nephrocalcinosis/nephrolithiasis; increased risk in premature infants and children under 4 
years without prematurity receiving chronic therapy  
• 
ototoxicity (eg, tinnitus, reversible/irreversible hearing impairment, deafness) has been 
reported; especially with rapid injection (infusion rate not to exceed 4 mg/min in adults), 
severe renal impairment, higher than recommended doses, hypoproteinemia, or 
concomitant ototoxic drugs (eg, aminoglycosides, ethacrynic acid)  
• 
patent ductus arteriosis, persistent; increased risk with administration to premature 
infants during first week of life  
• 
radiocontrast nephropathy, high-risk; increased risk of renal deterioration  
• 
renal damage may occur; monitoring recommended  
• 
severe progressive renal disease, preexisting; discontinue use if increase in azotemia 
and oliguria occur  
• 
sulfonamide allergy; increased risk of furosemide allergy  
• 
systemic lupus erythematosus, preexisting; risk of exacerbation or activation  
• 
urinary retention, severe; increased risk of acute urinary retention particularly during initial 
stages of treatment; monitoring recommended  
 
 
 

 
 
 
 
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GABAPENTIN 
Brand Name(s): Neurontin 
Adverse Effects 
Serious:  
• 
Dermatologic: Stevens-Johnson syndrome 
• 
Immunologic: Drug hypersensitivity syndrome 
• 
Neurologic: Drug-induced coma, Seizure (0.6%) 
• 
Psychiatric: Suicidal thoughts 
 
Common: 
• 
Cardiovascular: Peripheral edema (1.7% to 8.3%) 
• 
Gastrointestinal: Nausea (greater than 1%), Vomiting (3.3%) 
• 
Immunologic: Viral disease (10.9%) 
• 
Neurologic: Ataxia (3.3% to 12.5%), Dizziness (adults, 10.9% to 28%; pediatrics, 2.5%), 
Nystagmus (0.1% to 8.3%), Somnolence (4.5% to 21.4%) 
• 
Psychiatric: Hostile behavior (1% to 7.6%) 
• 
Other: Fatigue (3.4% to 11%), Fever (greater than 1%) 
 
Patient Information 
• 
Patient should avoid activities requiring mental alertness or coordination until drug effects 
are realized, as drug may cause dizziness and somnolence.  
• 
Drug may cause peripheral edema, myalgia, ataxia, nystagmus, tremor, or fatigue.  
• 
Advise patient to immediately report a rash or other signs/symptoms of hypersensitivity 
(eg, fever, lymphadenopathy).  
• 
Instruct patient or caregiver to report new or worsening depression, suicidal ideation, or 
unusual changes in behavior.  
• 
Advise patient against sudden discontinuation of drug, as this may increase seizure 
frequency or precipitate status epilepticus.  
• 
Gralise(R) should be taken with the evening meal . 
• 
Counsel patient using an antacid containing aluminum hydroxide and magnesium 
hydroxide to wait 2 hours before taking gabapentin.  
• 
This drug is available in multiple brand names with varying properties by brand. Instruct 
patients to follow dosing instructions specific to each brand. Gralise(R) specifically is not 
interchangeable with other gabapentin products.  
• 
Patient should avoid alcohol and other CNS depressants while taking this drug. 
 
Contraindications 
• 
hypersensitivity to gabapentin or any component of the product 
 
 
 
Precautions 
• 
abrupt discontinuation; may increase seizure frequency or precipitate status epilepticus; 
discontinue gradually over a minimum of 1 week  
• 
drug reaction with eosinophilia and systemic symptoms (DRESS)/multiorgan 
hypersensitivity, including fatal cases, has been reported; evaluate early signs/symptoms 
and discontinue Neurontin(R) if confirmed  
• 
gabapentin products are not interchangeable; differing pharmacokinetic profiles affect 
dosing frequency  

 
 
 
 
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• 
pediatric patients (age 3 to 12 years); neuropsychiatric adverse events, including 
emotional lability, hostility, thought disorder, and hyperkinesia, have been reported with 
Neurontin(R)  
• 
renal impairment or hemodialysis; dose adjustment of Neurontin(R) is necessary  
• 
renal impairment; dose adjustment may be required in mild to moderate impairment; do 
not administer Gralise(R) in patients with severe renal impairment (CrCl 15 to 30 mL/min) 
or on hemodialysis  
• 
suicidality, worsening depression, and/or any unusual behavioral or mood changes (eg, 
anxiety, agitation, hostility, mania, and hypomania); monitoring recommended  
• 
report suspected adverse reactions to the US Food and Drug Administration at 1-800-
FDA-1088 or www.fda.gov/medwatch 
 
 
 
Gefitinib 
 
Common 
Serious 
Ance (25% to 33%) 
Dry skin (13% to 26%) 
Pruritus (8% to 9%) 
Rash (43% to 54%) 
Weight loss (3% to 5%) 
Diarrhea (48% to 67%) 
Loss of appetite (7% to 10%) 
Nausea (13% to 18%) 
Vomiting (9% to 12%) 
Asthenia (4% to 6%) 
Tumor hemorrhage 
Hepatotoxicity 
Eye disorder 
New onset eye pain 
Aberrant eyelash 
Corneal erosion/ulcer 
Interstitial lung disease 
Interstitial pneumonia 
Pneumonitis (1%) 
Alveolitis (1%) 
 
This drug may cause acne, dry skin, loss of appetite, nausea, vomiting, or asthenia. 
 
Instruct patient to report diarrhea, skin rash, or signs/symptoms of hepatotoxicity or ocular 
toxicity (new onset eye pain, aberrant eyelash, corneal erosion/ulcer). 
 
Patient should also report signs/symptoms of myelosuppression. 
 
Advise patient to report respiratory issues such as signs/symptoms of interstitial pneumonia, 
pneumonitis, or pulmonary fibrosis. 
 
If patient vomits after taking drug, instruct patient to contact healthcare professional for 
instructions. 
 
Gemcitabine 
 
Gemcitabine 
 
Common 
Happens to 21-100 
children out of every 
100 
Occasional 
Happens to 5-20 children out 
of every 100 
Rare 
Happens to <5 children out of 
every 100 
Immediate: 
Within 1-2 
days of 
receiving drug 
Nausea, vomiting, 
fever, pain at the 
injection site, fluid build 
up in tissues causing 
swelling, flu-like 
symptoms, rash (L), 
mild diarrhea or 
Unnatural drowsiness (L), 
difficulty breathing 
Decreased blood pressure; a 
group of side effects: fever, 
decreased kidney function, low 
hemoglobin and platelets - 
which may result in death 

 
 
 
 
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constipation 
Prompt: 
Within 2-3 
weeks, prior to 
the next course 
Decrease in the number 
of red and white blood 
cells and platelets made 
in the bone marrow, 
decreased liver 
function, protein in the 
urine, blood in the urine 
Mouth sores, weakness (L) 
Kidney toxicity, confusion, 
seizure (L), coma (L), fluid 
buildup in the lungs, - unrelated 
to heart function, which occurs 
very rarely but may be fatal 
Delayed: 
Any time later 
during therapy, 
excluding the 
above 
conditions 
 
Hair loss, numbness or 
tingling, itching 
 
Late: 
Any time after 
completion of 
treatment 
 
 
 
(L) Toxicity may also occur later. 
 
 
GENTAMICIN SULFATE 
Brand Name(s): Gentak ; Gentasol 
Adverse Effects 
Serious:  
• 
Neurologic: Neuromuscular blockade finding 
• 
Otic: Ototoxicity 
• 
Renal: Nephrotoxicity 
• 
Respiratory: Respiratory tract paralysis, Concomitant anesthesia, muscle relaxants 
 
Common: 
• 
None indicated 
 
Patient Information 
• 
Instruct patient to maintain adequate fluid intake and avoid dehydration during drug 
therapy, as this may increase risk for toxicity. 
• 
Instruct patient to report signs/symptoms of ototoxicity or nephrotoxicity. 
• 
Instruct patient on proper instillation technique for ophthalmic preparation. 
 
Contraindications 
• 
hypersensitivity to gentamicin/aminoglycosides 
 
Precautions 
• 
pre-existing renal, vestibular, or auditory impairment 
• 
concomitant anesthesia or neuromuscular blockers; risk for neuromuscular blockade, 
respiratory paralysis 
• 
concomitant neurotoxic, ototoxic, or nephrotoxic drugs, age (very young/very old), and 
dehydration; risk factor for toxicity 
 
 

 
 
 
 
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GRISEOFULVIN 
Brand Name(s): Grifulvin ; Gris-PEG 
Adverse Effects 
Serious:  
• 
Neurologic: Acroparesthesia (rare) 
 
Common: 
• 
Dermatologic: Photosensitivity, Rash, Urticaria 
• 
Gastrointestinal: Diarrhea, Nausea, Vomiting 
• 
Neurologic: Headache 
 
Patient Information 
• 
Drug may cause sun-sensitivity. Advise patient to use sunscreen and avoid tanning beds. 
• 
Adverse effects to a fetus may be caused by either male or female patients receiving 
treatment with this drug. Emphasize the use of reliable contraception to patient. This 
applies during treatment and up to 1 month post therapy for women and 6 months post 
therapy for men. 
• 
This drug may cause rash, urticaria, diarrhea, nausea, vomiting, or headache. 
 
Contraindications 
• 
hepatocellular failure  
• 
hypersensitivity to griseofulvin  
• 
porphyria  
• 
pregnancy  
 
Precautions 
• 
alcohol use; griseofulvin may potentiate effects (eg, tachycardia, flush)  
• 
hepatotoxicity (jaundice and elevation in ALT, AST, and bilirubin), including serious and 
fatal cases, has been reported; monitoring recommended; discontinuation may be 
necessary  
• 
lupus erythematosus or lupus-like syndromes have been reported  
• 
penicillin allergy; potential for cross-sensitivity with penicillin  
• 
photosensitivity may occur; avoid excessive exposure to sunlight  
• 
serious skin reactions (eg, Stevens-Johnson syndrome and toxic epidermal necrolysis) 
and erythema, including serious and fatal cases, have been reported; discontinuation if 
severe skin reactions occur  
 
 
 
 

 
 
 
 
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GUAIFENESIN 
Brand Name(s): Mucinex 
Adverse Effects 
Serious:  
• 
None indicated 
Common: 
• 
Gastrointestinal: Nausea, Vomiting 
 
Patient Information 
• 
This drug may cause nausea or vomiting. 
• 
Patient should take drug with a full glass of water and maintain adequate hydration during 
drug therapy. 
• 
Instruct patient that guaifenesin in combination with dextromethorphan should not be 
used in patients taking MAO inhibitors. 
• 
Advise patients with history of cardiac disorder, diabetes, peripheral vascular disease, 
prostatic hypertrophy, or glaucoma to avoid guaifenesin in combination with 
phenylpropanolamine.  
 
Contraindications 
• 
hypersensitivity to guaifenesin products 
 
Precautions 
• 
cough accompanied by too much mucus 
• 
guaifenesin in combination with dextromethorphan should not be used in patients taking 
MAOI's 
• 
guaifenesin in combination with phenylpropanolamine should be used with caution in 
patients with hypertension, cardiac disorders, diabetes or peripheral vascular disease, 
prostatic hypertrophy and glaucoma 
• 
persistent or chronic cough such as that which occurs with smoking, asthma, chronic 
bronchitis, or emphysema 
 
 
GUANETHIDINE MONOSULFATE 
Brand Name(s): Intuniv ; Tenex 
Adverse Effects 
Serious:  
• 
Cardiovascular: Bradyarrhythmia (ADHD, 2% ; hypertension, 3% or less .), Hypotension 
(ADHD, 3% to 7%), Syncope (ADHD, 1% ; hypertension, less than 1%) 
• 
Dermatologic: Peeling of skin 
• 
Neurologic: Seizure 
 
Common: 
• 
Cardiovascular: Orthostatic hypotension (ADHD, 1% ; hypertension, 15%) 
• 
Gastrointestinal: Abdominal pain (ADHD, 10% to 11%), Constipation (ADHD, 2% to 3%; 
hypertension, up to 15%), Xerostomia (ADHD, 2% to 4%; hypertension 5% to 54%) 
• 
Neurologic: Dizziness (ADHD, 6% to 8% ; hypertension, 1% to 15%), Headache (ADHD, 
21% to 24% ; hypertension, 1% to 13%), Insomnia (ADHD, 12% ; hypertension, 4%), 
Somnolence (ADHD, 18% to 38% ; hypertension, up to 39%) 
• 
Reproductive: Impotence (hypertension, up to 7%) 
• 
Other: Fatigue (ADHD, 10% to 14% ; hypertension 2% to 10%) 
 

 
 
 
 
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Patient Information 
• 
Patient should avoid activities requiring mental alertness or coordination until drug effects 
are realized, as drug may cause dizziness or somnolence.  
• 
Advise patient to use caution with activities leading to an increased core temperature to 
avoid dehydration, orthostatic hypotension, and syncope.  
• 
Drug may cause sedation, hypotension, dry mouth, headache, fatigue, constipation, or 
abdominal pain.  
• 
Advise patient against sudden discontinuation of drug, as this may cause rebound 
hypertension.  
• 
Patient should not drink alcohol or take CNS depressants with this drug.  
• 
Tell patient to contact healthcare professional for instructions if more than 2 successive 
doses are missed as titration may be necessary.  
 
Contraindications 
• 
hypersensitivity to guanfacine or to any component of the product  
 
Precautions 
• 
abrupt withdrawal; risk of rebound hypertension  
• 
blood pressure decreases have been reported; monitoring recommended  
• 
bradycardia, history; risk of decreased blood pressure and heart rate  
• 
cardiovascular disease, history; risk of decreased blood pressure and heart rate  
• 
concomitant use of alcohol; should be avoided  
• 
concomitant use of other guanfacine-containing products (eg, Tenex(R)); do not use  
• 
dehydration or becoming overheated; risk of decreased blood pressure and heart rate  
• 
heart block, history; risk of decreased blood pressure and heart rate  
• 
heart rate decreases have been reported; monitoring recommended  
• 
hypotension, history; risk of decreased blood pressure and heart rate  
• 
sedation and somnolence have been reported; consider potential for additive effects 
before coadministering centrally active depressants (eg, phenothiazine, barbiturates, or 
benzodiazepines)  
• 
syncope has been reported; increased risk in patients with history or predisposition (eg, 
hypotension, orthostatic hypotension, bradycardia, or dehydration)  
• 
report suspected adverse reactions to Shire US Inc. at 1-800-828-2088 or to the US Food 
and Drug Administration at 1-800-FDA-1088 or www.fda.gov/medwatch  
 
HYDROXYUREA 
Brand Name(s): Droxia  ;  Hydrea  ;  Mylocel 
Adverse Effects 
Serious:  
• 
Dermatologic: Gangrenous disorder, Skin cancer, Skin ulcer 
• 
Hematologic: Genetic mutation, Long-term use, Secondary leukemia, Long-term use 
 
Common: 
• 
Hematologic: Myelosuppression 
 
Patient Information 
• 
Adverse effects to a fetus may be caused by either male or female patients receiving 
treatment with this drug. Emphasize the use of reliable contraception to patient. This 
applies during treatment and up to 6 months post-therapy. 

 
 
 
 
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• 
Instruct patient to avoid vaccines during therapy due to drug-induced 
immunosuppression. 
• 
Advise patient on the proper handling and disposal of chemotherapy drugs. 
• 
This drug may cause skin ulcers. 
• 
Counsel patient to report signs/symptoms of myelosuppression, especially in patients 
receiving radiotherapy or cancer chemotherapy. 
• 
Advise HIV-infected patients receiving concomitant didanosine and/or stavudine to report 
signs/symptoms of pancreatitis and hepatotoxicity. 
 
Contraindications 
• 
hypersensitivity to hydroxyurea or any component of the product  
• 
significant bone marrow depression, such as leukopenia, thrombocytopenia or severe 
anemia (Hydrea(R))  
 
Precautions 
• 
causes macrocytosis which may mask development of folic acid deficiency (prophylactic 
folic acid recommended with Droxia(R) therapy)  
• 
correct severe anemia prior to initiating hydroxyurea therapy  
• 
cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene; reported in 
patients with myeloproliferative disorders and receiving interferon therapy  
• 
elderly patients; increased sensitivity to effects  
• 
exacerbation of postirradiation erythema  
• 
HIV-infected patients; hepatotoxicity, hepatic failure, pancreatitis, some fatal, and severe 
peripheral neuropathy have been reported; avoid combination of hydroxyurea, didanosine 
and stavudine  
• 
hydroxyurea is mutagenic and clastogenic; secondary leukemias have occurred with 
long-term therapy for myeloproliferative disorders  
• 
myelosuppression; especially in patients previously receiving radiotherapy or cancer 
chemotherapy  
• 
renal impairment; initial dose reduction required  
 
Ibuprofen 
 
Common 
Serious 
Hypotension (intravenous, up to 10%) 
Rash (oral, 3% to 9%) 
Hypernatremia (intravenous, up to 10%) 
Hypoalbuminemia (intravenous, 3% to 10%) 
 Hypoproteinemia (intravenous, up to 13%) 
Serum lactate dehydrogenase level elevated 
(intravenous, 3% to 10%) 
Flatulence (injection, 7% to 16%) 
 Heartburn (oral, 3% to 9%) 
 Nausea (oral, 3% to 9%; intravenous, 53% to 
57%) 
Vomiting (oral, 1% to 3%; intravenous, 15% to 
22%) 
Congestive heart failure (oral, less than 1%),  
Hypertension (oral, less than 1%; intravenous, up 
to 10%),  
Myocardial infarction,  
Thrombotic tendency observations 
Erythema multiforme (oral, less than 1%.),  
Erythroderma, 
 Stevens-Johnson syndrome (oral, less than 1%), 
Toxic epidermal necrolysis 
Gastrointestinal hemorrhage (oral, less than 1%),  
Gastrointestinal perforation (oral, less than 1%),  
Gastrointestinal ulcer,  
Inflammatory disorder of digestive tract,  

 
 
 
 
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Thrombocytosis (intravenous, 3% to 10%) 
Bacteremia (injection, 13%) 
Dizziness (oral, 3% to 9%; intravenous 4% to 6%) 
Headache (oral, 1% to 3%; intravenous, 9% to 
11%) 
Serum blood urea nitrogen raised (intravenous, up 
to 10%)  
Urinary retention (intravenous, 3% to 5%) 
Bacterial pneumonia (intravenous, 3% to 10%) 
 
Melena (oral, less than 1%),  
Pancreatitis (oral, less than 1%) 
Agranulocytosis (oral, less than 1%),  
Anemia (intravenous, 2% to 36%),  
Aplastic anemia (oral, less than 1%),  
Bleeding (intravenous, 4% to 10%),  
Hemolytic anemia (oral, less than 1%),  
Neutropenia (intravenous, 7% to 13%; oral, less 
than 1%),  
Thrombocytopenia (less than 1%),  
Wound hemorrhage (intravenous, 1% to 3%) 
Fulminant hepatitis (rare),  
Hepatic necrosis (rare),  
Hepatitis (oral, less than 1%),  
Hepatotoxicity (rare),  
Jaundice (oral, less than 1%),  
Liver failure (rare),  
Vanishing bile duct syndrome 
Anaphylactoid reaction (oral, less than 1%),  
Immune hypersensitivity reaction (oral, less than 
1%) 
Aseptic meningitis (oral, less than 1%),  
Cerebrovascular accident 
Amblyopia (oral, less than 1%) 
Hearing loss (oral, less than 1%) 
Depression (oral, less than 1%) 
Acute renal failure (oral, less than 1%),  
Hematuria (oral, less than 1%),  
Renal azotemia (oral, less than 1%) 
Reye's syndrome 
 
 
Advise patient to avoid use of additional NSAIDs or aspirin during therapy, unless approved 
by doctor.  
 
Advise patient to avoid use in late pregnancy as drug may cause premature closure of ductus 
arteriosus.  
 
Drug may cause fluid retention, abdominal pain, constipation, diarrhea, dyspepsia, heartburn, 
nausea, vomiting, dizziness, headache and hemorrhage.  
 
Advise patient with previous cardiac history to report signs/symptoms of myocardial infarction 
or stroke, especially with long-term use.  
 
Instruct patient to report signs/symptoms of serious gastrointestinal events, such as bleeding, 
ulceration, or perforation. Elderly and debilitated patients may be at increased risk.  
 
Instruct patient to report signs/symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, 
jaundice, right upper quadrant tenderness, and flu-like symptoms).  
 
Patient should promptly report skin rash, blistering, or any symptoms of a serious skin reaction.  
 
Tell patient to take oral form with food or milk to minimize GI irritation.  

 
 
 
 
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 
Patient should not drink alcohol or smoke while using this drug to reduce risk of GI bleeds.  
 
 
Imatinib 
 
Risks and side effects related to  Gleevec (imatinib mesylate include): 
 
Common 
Happens to 21-100 
children out of every 
100 
Occasional 
Happens to 5-20 
children out of every 
100 
Rare 
Happens to <5 children out of every 
100 
Immediate: 
Within 1-2 days of 
receiving drug 
Heartburn, 
nausea/vomiting, 
headache, fluid buildup 
in the arms, legs, face, 
or around the eyes (L), 
weight gain 
Fever,), increase in liver 
enzymes 
(SGOT, 
SGPT, 
alkaline 
phosphatase) 
and 
bilirubin 
indicating 
possible liver damage 
(L),, 
abdominal 
pain/cramping, muscle 
and joint pain (L) 
Swelling of the brain, breakdown of 
bone (L), inflammation of the lung 
and/or damage to the lungs (L) 
Prompt: 
Within 2-3 weeks, 
prior to the next 
course 
Decrease in numbers 
of red and white blood 
cells and platelets 
made in bone marrow 
(L), fatigue 
Decreased number of 
bone marrow cells (L), 
scaly and/or itchy rash, 
rash, muscle pain and 
cramping, 
loss 
of 
appetite 
Dark, bloody bowel movements, 
diarrhea, difficulty swallowing, 
inflammation of the passage 
between the throat and stomach,  
pain during swallowing,widespread 
red itching rash , bleeding, vomiting 
blood 
Delayed: 
Any time later 
during therapy, 
excluding the above 
condition 
 
Skin color changes, 
usually lighter patches 
Liver Damage (L)* 
Late: 
Any time after the 
completion of 
treatment 
 
 
 
(L) Side effect may also occur later 
*  
One patient with no known history of liver problems died on study due to liver failure. 
This patient was also taking acetaminophen (Tylenol®), also known as paracetamol in 
European countries. It is recommended you adhere carefully to the instructions and 
warnings on the acetaminophen package label.  Additionally, it is recommended that 
over-the-counter medications be carefully reviewed, as these may possibly contain 
combinations of drugs, including acetaminophen or paracetamol. 
 
 
Since there is an increased risk of bleeding when taking imatinib mesylate 
(Gleevec), the blood anticoagulant warfarin sodium must not be taken. Your doctor will discuss 
alternatives with you. However, even when alternative anti clotting drugs are used it will be 
necessary to closely watch for bleeding and to maintain platelet counts at a safe level with 
transfusion if necessary.  Bleeding may occur into a tumor or a space near the tumor and may be 
dangerous. 
 
 
 

 
 
 
 
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Indomethacin 
 
Common 
Serious 
Abdominal pain (1% to 3%), 
Constipation (1% to 3%),  
Diarrhea (1% to 3%),  
ndigestion (3% to 9%),  
Nausea (3% to 9%) 
Dizziness,  
Headache,  
Somnolence 
Tinnitus 
Depression 
Fatigue 
 
Cardiac dysrhythmia (less than 1%),  
Chest pain (less than 1%),  
Congestive heart failure (less than 1%),  
Edema (less than 1%),  
Hypertension (less than 1%),  
Myocardial infarction 
Erythema multiforme (less than 1%),  
Rash (less than 1%),  
Scaling eczema,  
Stevens-Johnson syndrome (less than 1%),  
Toxic epidermal necrolysis (less than 1%) 
Hyponatremia,  
Transitory neonatal hyperkalemia (3-9%) 
Gastrointestinal hemorrhage (less than 1%),  
Gastrointestinal perforation (less than 1%),  
Gastrointestinal ulcer (less than 1%),  
Inflammatory disorder of digestive tract (less than 
1%) 
Agranulocytosis (less than 1%),  
Anemia (less than 1%),  
Aplastic anemia,  
Leukopenia (less than 1%),  
Neutropenia,  
Thrombocytopenic purpura (less than 1%) 
Hepatitis (less than 1%),  
Jaundice (less than 1%),  
Liver failure 
IAnaphylactoid reaction (less than 1%) 
Cerebrovascular accident,  
Epilepsy,  
Aggravation,  
Parkinsonism,  
Aggravation (less than 1%), 
Peripheral neuropathy (less than 1%),  
Seizure (less than 1%) 
Blurred vision (less than 1%),  
Corneal deposit (less than 1%),  
Retinal disorder (less than 1%) 
Hearing loss (less than 1%) 
Psychic disease (less than 1%) 

 
 
 
 
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Hematuria (less than 1%),  
Interstitial nephritis (less than 1%), 
Nephrotic syndrome (less than 1%),  
Newborn renal dysfunction (41%),  
Renal failure (less than 1%) 
Asthma (less than 1%),  
Bronchospasm (less than 1%),  
Dyspnea (less than 1%),  
Persistent pulmonary hypertension of the newborn 
(<3%),  
Pulmonary edema (less than 1%) 
 
Patient should avoid activities requiring mental alertness until drug effects are realized, as drug 
may cause somnolence. 
 
This drug may cause abdominal pain, anal irritation, constipation, diarrhea, dyspepsia, nausea, 
tenesmus, vomiting, dizziness, headache, tinnitus, depression, scaling eczema, or fatigue. 
 
Instruct patient to report signs/symptoms of a serious cardiovascular thrombotic event, such as 
myocardial infarction or stroke. Patients with cardiovascular disease or on prolonged therapy 
may be at increased risk for this adverse effect. 
 
Advise patients to report signs/symptoms of a serious gastrointestinal adverse event, such as 
bleeding, ulceration, or perforation of the stomach or intestines. Elderly or debilitated patients 
may be at increased risk for this adverse effect. 
 
Patient should take the oral formulations with food, immediately after meals, or with antacids. 
 
Patient should not use other NSAIDs concomitantly without approval by healthcare 
professional. 
 
IRINOTECAN HYDROCHLORIDE 
Brand Name(s): Camptosar 
Adverse Effects 
Serious:  
• 
Cardiovascular: Disorder of cardiovascular system 
• 
Gastrointestinal: Diarrhea, Grade 3 and 4 (4.9% to 31%), Gastrointestinal perforation 
• 
Hematologic: Anemia, Grade 3 and 4 (2.1% to 8.4%), Febrile neutropenia (adults, 2% to 
7.1%; pediatrics, 8.8%), Hemorrhage (1% to 5%), Infectious disease, Neutropenic (1% to 
2.2%), Leukopenia, Grade 3 and 4 (17.4% to 37.8%), Neutropenia, Grade 3 or 4 (adults, 
26% to 53.8%; pediatrics, 31.8%), Thrombocytopenia, Grade 3 and 4 (up to 4%), 
Thromboembolic disorder (5.4% to 11.7%) 
• 
Immunologic: Hypersensitivity reaction 
• 
Respiratory: Interstitial lung disease 
 
Common: 
• 
Dermatologic: Alopecia (43.1% to 60%) 
• 
Endocrine metabolic: Weight decreased (30%) 
• 
Gastrointestinal: Abdominal pain (all grade, 17.2% to 67.7%; grade 3 and 4, 2.1% to 
14%), Constipation (all grade, 30% to 43.9%; grade 3 and 4, 0.4% to 10%), Diarrhea, All 
grade (early-onset, 43% to 51%; late-onset, 72.4% to 88%), Loss of appetite (all grade, 
34.2% to 55%; grade 3 and 4, 2.1% to 7.2%), Nausea (all grade, 66.9% to 86%; grade 3 
and 4, 2.1% to 17%), Vomiting (all grade, 44.8% to 67%; grade 3 and 4, 3.5% to 14%) 

 
 
 
 
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• 
Hematologic: Anemia, All grade (60% to 97.2%), Drug-induced eosinophilia, 
Leukopenia, All grade (63% to 96.9%), Neutropenia, All grade (54% to 96.9%), 
Thrombocytopenia, All grade (32.6% to 96%) 
• 
Hepatic: Increased bilirubin level (19.1% to 87.6%) 
• 
Neurologic: Asthenia (all grade, 57.9% to 76%; grade 3 and 4, 9% to 19.5%), Dizziness 
(15% to 23.1%) 
• 
Respiratory: Cough (17% to 26.7%), Dyspnea (9.7% to 27.6%) 
• 
Other: Fever (42.2% to 45%), Infectious disease (13.9% to 35.9%), Pain (all grade, 
22.9% to 64.1%; grade 3 and 4, 2% to 19%), Poisoning by parasympathomimetic drug 
(28.3%) 
 
Patient Information 
• 
Drug may cause dizziness or visual disturbances, especially within 24 h after infusion. 
Patient should avoid driving or other activities requiring clear vision until drug effects are 
realized. 
• 
Advise patient to avoid vaccines during therapy due to drug-induced immunosuppression. 
• 
This drug may cause alopecia, nausea, vomiting, or interstitial lung disease. 
• 
Instruct patient to report diarrhea that occurs during or shortly after infusion. Inform 
patient that diarrhea may be accompanied by cholinergic symptoms of rhinitis, increased 
salivation, miosis, lacrimation, diaphoresis, flushing, or abdominal cramping. 
• 
Patient should also report diarrhea that occurs more than 24 h after drug infusion. Instruct 
patient to take anti-diarrheal medicine only as prescribed by healthcare professional. 
• 
Patient should contact healthcare professional if diarrhea cannot be controlled within 24 
h, nausea/vomiting precludes patient from taking liquids, or patient has signs/symptoms 
of dehydration or infection. 
 
Contraindications 
• 
hypersensitivity to irinotecan or any component of the product  
 
Precautions 
• 
diarrhea, early or late; may be life-threatening due to possible dehydration, electrolyte 
imbalance, and sepsis  
• 
bilirubin levels, elevated serum (1 to 2 mg/dL); increased risk for first cycle, grade 3 or 4 
neutropenia  
• 
bone marrow failure, severe; potential for neutropenia, leucopenia, and anemia  
• 
concomitant use with live vaccine; avoid use  
• 
elderly patients, greater than 65 years of age; increased risk of late diarrhea  
• 
hepatic insufficiency; deficient glucuronidation of bilirubin (Gilbert's syndrome), increased 
risk of myelosuppression  
• 
hereditary fructose intolerance; Camptosar(R) contains sorbitol  
• 
homozygous for UGT1A1*28 allele ; increased risk of neutropenia; testing of the UGT1A1 
6/6, 6/7 and 7/7 genotypes may be considered  
• 
interstitial pulmonary disease (IPD)-like events, including fatalities, have been reported; 
hold therapy for any suspicious symptoms pending diagnostic evaluation  
• 
Mayo Clinic regimen (5-fluorouracil/leucovorin) concomitant use; especially in patients 
receiving treatment with pelvic/abdominal radiation, elderly with comorbidities; may result 
in increased risk of neutropenic fever, hospitalization, thromboembolism, first-cycle 
treatment discontinuation, early death, toxicity, including toxic death  
• 
myelosuppression, severe 
• 
neutropenia; may lead to sepsis and death; dose reduction may be necessary  

 
 
 
 
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• 
vomiting and/or severe diarrhea; leading to volume depletion and increased risk of renal 
impairment and acute renal failure  
 
 
Ixabepilone 
 
Ixabepilone has been tested in more than one thousand adults, and risks and side 
effects related to Ixabepilone in adults include: 
Likely 
Less Likely 
Rare but Serious 
• 
A feeling of 
weakness 
and/or 
tiredness 
• 
Loss of 
appetite or 
desire to eat  
• 
Nausea, and/or 
vomiting 
• 
Diarrhea 
• 
Inflammation 
and/or sores in 
the mouth that 
may make 
swallowing 
difficult and 
are painful 
(painful mouth 
sores) 
• 
Hair loss 
• 
Muscle and 
joint pains 
• 
A problem in 
nerve function 
that may cause 
pain, 
numbness, 
tingling, and 
muscle 
weakness in 
various parts 
of the body. 
 
• 
Allergic reactions 
• 
Fever caused by the medication  
• 
Fewer white blood cells, red 
blood cells and platelets in the 
blood 
o 
a low number of white blood 
cells can make it easier to 
get infections 
o 
a low number of red blood 
cells can make you feel tired 
and weak 
o 
a low number of platelets 
causes you to bruise and 
bleed more easily 
• 
Constipation 
• 
A slower than normal heart rate 
• 
Chest pain which may be 
caused by heart damage 
• 
Heart attack 
• 
An increased level of a protein 
in the blood which is found in 
heart muscle and when 
elevated may indicate a heart 
attack or heart damage that 
could lead to a heart attack 
• 
A decrease in blood pressure  
• 
Change in the ability of the 
blood to clot if you are on a 
drug called warfarin or 
coumadin. You will need to be 
closely followed if you are on 
this medication. 
• 
Weight loss 
• 
Reddening of the face with 
feelings of warmth 
• 
Dizziness or fainting 
• 
Difficulty sleeping or falling 
asleep  
• 
Damage to the skin if the 
medication leaks from the vein  
• 
Changes to your finger or 
toenails 
• 
Itching 
• 
Redness and burning at sites 
which have received radiation 
in the past 
• 
Allergic reactions which 
can be life threatening 
with shortness of breath, 
low blood pressure, rapid 
heart rate, hives and 
facial swelling 
• 
A condition in which fluid 
and proteins leak out of 
tiny blood vessels and 
flow into surrounding 
tissues, resulting in 
dangerously low blood 
pressure. Vascular or 
capillary leak syndrome 
may lead to multiple 
organ failure such as 
kidney, heart or liver 
failure and shock 
• 
Fluid build-up in the 
lungs that can make you 
feel short of breath. 
• 
A stoppage (or blockage) 
of the intestine which 
may require treatment 
• 
 

 
 
 
 
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• 
Rash with peeling of the skin 
• 
Severe rash with redness and 
pain on the palms of the hand 
and soles of the feet 
• 
Excessive loss of water from 
the body 
• 
Difficulty or discomfort on 
swallowing 
• 
Inflammation and/or sores in 
the throat and/or esophagus 
(the tube between the mouth 
and the stomach) that may 
make swallowing difficult and 
are painful 
• 
Upset stomach (heartburn) 
• 
Things taste differently 
• 
Erosion (ulceration) of the 
lining of the intestines which 
can result in pain and/or 
bleeding 
• 
Bleeding from the intestines 
• 
Damage to the liver which 
could lead to liver failure 
• 
Fever with a low white blood 
cell count which could indicate 
infection and may require 
hospitalization and treatment 
with antibiotics 
• 
Infections including those 
caused by bacteria, virus, and 
fungus 
• 
Fluid build-up in the tissues of 
the head, neck, arms, legs, 
body, abdomen (belly), body 
and sex organs 
• 
Increased levels of a chemical 
(creatinine) in the blood which 
could mean kidney damage 
• 
Unsteadiness when walking 
• 
Inability to speak or difficulty 
with speaking or putting words 
together  
• 
Watery eyes (tearing) 
• 
Abdominal (belly) pain 
• 
Bone pain 
• 
Headache 
• 
Arm or leg pain 
• 
Tumor pain 
• 
Muscle weakness 
• 
Hiccoughs 
• 
Cough 
• 
Feeling short of breath or 
shortness of breath 
• 
Low levels of oxygen in the 
blood which may make you feel 
10/01/07 

 
 
 
 
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short of breath 
• 
Inflammation of the lungs that 
can lead to fluid in the lungs 
and affect your ability to 
breathe and the levels of 
oxygen in your blood making 
you short of breath 
• 
Difficulty emptying the bladder 
which may be caused by nerve 
damage 
• 
Lowered amount of salt 
(sodium) in the blood 
 
The side effects that occurred in the adult patients may or may not occur in children 
entered on this study.  
 
Ketoprofen 
 
Common 
Serious 
Edema 
Rash 
Abdominal pain,  
Constipation,  
Diarrhea,  
Flatulence,  
Indigestion,  
Nausea 
Dizziness,  
Headache, 
Insomnia 
Tinnitus 
Congestive heart failure (<1%), 
 Hypertension (<1%), 
 Myocardial infarction (<2%), 
Thrombotic tendency observations 
Scaling eczema, 
Stevens-Johnson syndrome (<0.1%) 
Gastrointestinal hemorrhage (<1%), 
Gastrointestinal perforation (<1%), 
Inflammatory disorder of digestive tract, 
Melena (<1%) 
Agranulocytosis (<1%), 
Anemia (<1%), 
Thrombocytopenia (<1%) 
Hepatitis (<1%), 
Increased liver function test (up to 15%), 
Jaundice (<1%), 
Liver failure (<0.1%) 
Anaphylactoid reaction (<1%), 
Immune hypersensitivity reaction 
Cerebrovascular accident 
Impaired renal function disorder (3-9%), 
Interstitial nephritis (<1%), 
Renal failure (<1%) 
Bronchospasm (<2%) 
 
This drug may cause edema, abdominal pain, constipation, diarrhea, dyspepsia, flatulence, 
nausea, dizziness, headache, insomnia, or tinnitus. 

 
 
 
 
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 
Patients with a history of cardiac disease or on a long-term treatment regimen are at an 
increased risk for adverse cardiovascular thrombotic events. Advise patient to report 
signs/symptoms of myocardial infarction or stroke.  
 
Instruct patients to report signs/symptoms of serious gastrointestinal events such as bleeding, 
ulceration, or perforation of stomach or intestines. Elderly and debilitated patients may be at an 
increased risk for this adverse effect. 
 
Patient may take with food, milk, or antacids to minimize gastrointestinal irritation. 
 
Advise patient to avoid use of additional NSAIDs without healthcare professional approval.  
 
Patient should not drink alcohol while taking this drug. 
 
Ketorolac 
 
Common 
Serious 
Edema,  
Hypertension 
Injection site pain,  
Pruritus,  
Rash,  
Sweating 
Abdominal pain (13%),  
Diarrhea (7%),  
Indigestion (12%),  
Nausea (12%) 
Anemia 
Dizziness,  
Headache,  
Somnolence 
Burning sensation in eye, Transient,  
ophthalmic ketorolac (20% to 40%, ophthalmic), 
  Corneal edema (1% and 10%, ophthalmic),  
  Eye irritation, Iritis (1% and 10%, ophthalmic),  
  Keratitis (1% and 10%, ophthalmic) 
Feeling nervous 
 
Myocardial infarction,  
Thrombotic tendency observations 
Body pale (<1%),  
Erythema multiforme, 
 Erythroderma,  
Stevens-Johnson syndrome,  
Toxic epidermal necrolysis 
Gastrointestinal hemorrhage,  
Gastrointestinal perforation,  
Gastrointestinal ulcer,  
Melena,  
Pancreatitis (rare (incidence less than 0.1%)  
HBleeding,  
Blood coagulation disorder with prolonged 
bleeding time,  
Hematoma,  
Postoperative hemorrhage 
Hepatitis,  
Increased liver function test,  
Jaundice, Liver failure 
Anaphylactoid reaction 
Aseptic meningitis,  
Cerebrovascular accident 
Corneal epithelial degeneration,  
Corneal erosion,  
Corneal thinning,  
Perforation of cornea 
Hearing loss 
Hematuria,  
Hemolytic uremic syndrome,  
Interstitial nephritis,  
Nephrotic syndrome,  

 
 
 
 
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Papillary necrosis,  
Proteinuria,  
Renal failure 
Asthma,  
Bronchospasm,  
Dyspnea,  
Pulmonary edema 
Angioedema 
 
This drug may cause edema, sweating, abdominal pain, constipation, diarrhea, dyspepsia, 
flatulence, nausea, stomatitis, vomiting, anemia, dizziness, headache, or somnolence. The 
ophthalmic formulation may cause a burning sensation in the eye. 
 
Patients with a history of cardiac disease or on a long-term regimen are at an increased risk for 
adverse cardiovascular thrombotic events. Advise patient to report signs/symptoms of 
myocardial infarction or stroke.  
 
Instruct patients to report signs/symptoms of serious gastrointestinal events such as bleeding, 
ulceration, or perforation of stomach or intestines. Elderly and debilitated patients may be at an 
increased risk for this adverse effect. 
 
Advise patients using the ophthalmic formulation to remove contact lenses prior to instilling 
drug. Lenses may be reinserted 15 min following instillation. 
 
Advise patient to avoid use of additional NSAIDs without healthcare professional approval. 
 
Patients using the ophthalmic formulation should avoid concomitant use of topical steroids. 
 
Lansoprazole 
 
Common 
Serious 
Abdominal pain (up to 5%),  
Constipation (1% to 5%),  
Diarrhea (up to 7.4%),  
Nausea (1.3% to 3%) 
Vomiting  
Taste sense altered 
Dyspepsia  
Headache 
Fatigue 
 
Fracture of bone, Osteoporosis-related,  
Hip fracture,  
Rhabdomyolysis 
 
 
    This drug may cause abdominal pain, constipation, diarrhea, dyspepsia, loss of appetite, 
nausea, vomiting, altered taste, headache, or fatigue. 
 
Patient should take oral preparations before eating.  
 
Lapatinib 
 
Common 
Serious 
Hand-foot syndrome due to cytotoxic therapy 
(53%),  
Rash (28% to 31%) 
Depression of left ventricular systolic function 
(1.3% to 2%),  
Prolonged QT interval 

 
 
 
 
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Diarrhea (42% to 65%),  
Indigestion (11%),  
Nausea (13% to 44%),  
Vomiting (26%) 
Anemia (56%),  
Thrombocytopenia (18%) 
ALT (SGPT) level raised (37%), 
 AST/SGOT level raised (49%),  
Hyperbilirubinemia (45%) 
Backache (11%),  
Pain in limb (12%) 
Insomnia (10%) 
Dyspnea (12%) 
 
Hepatotoxicity (less than 1%) 
Interstitial lung disease 
 
 
Advise patient on the proper handling and disposal of chemotherapy drugs. 
 
This drug may cause gastrointestinal (nausea and vomiting) and dermatological (palmar-
plantar erythrodysesthesia and rash) adverse events and fatigue. 
 
Instruct patient to report severe diarrhea and consult a healthcare professional prior to taking 
antidiarrheal medicine. 
 
Patient should report signs/symptoms of interstitial lung disease, pneumonitis, or decreased left 
ventricular ejection fraction (eg, dyspnea, palpitation, and/or fatigue). 
 
Advise patient to take this drug at least one hour before or one hour after a meal. In contrast, 
capecitabine should be taken with food or within 30 minutes after food. 
 
Patient should not eat grapefruit or drink grapefruit juice while taking this drug. 
 
Leflunomide 
 
Common 
Serious 
Alopecia (10%),  
Rash (10%) 
Diarrhea (17%) 
 
Hypertension (9% to 10%; new-onset, 1% to 2%) 
Stevens-Johnson syndrome (rare),  
Toxic epidermal necrolysis (rare) 
Agranulocytosis (rare),  
Pancytopenia (rare) 
Hepatic necrosis (rare),  
Hepatotoxicity (rare),  
Increased liver enzymes,  
Liver failure (rare) 
Anaphylaxis,  
Opportunistic infection,  
Sepsis 
Interstitial lung disease (rare) 
 
Adverse effects to a fetus may be caused by either male or female patients receiving treatment 
with this drug. Emphasize the use of reliable contraception to patient. If pregnancy is desired or 
suspected in females, or males wishing to father a child, a drug elimination procedure may be 

 
 
 
 
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employed in order to rapidly remove leflunomide from the body. Consult healthcare 
professional. 
 
Advise patient to avoid vaccines during therapy without healthcare professional approval. 
 
This drug may cause rash, alopecia, diarrhea, or hypertension. 
 
Instruct patient to report signs/symptoms of hepatotoxicity, especially if using concomitant 
methotrexate. 
 
Advise patient to report signs/symptoms of a severe skin reaction such as Stevens-Johnson 
syndrome (flu-like symptoms, spreading red rash, or skin/mucous membrane blistering) or 
toxic epidermal necrolysis (widespread peeling/blistering of skin). 
 
Tell patients with a history of or active hematological abnormalities to monitor for and report 
signs/symptoms of pancytopenia. 
 
Lenalidomide (CC-5013) 
 
 
We know about the following side effects of CC-5013:  
 
 
 
The main side effects that were seen in adults taking this drug were low blood counts, 
itchiness, and rash.  All the bad effects, both common and uncommon, that have been 
seen so far in people getting this drug are listed below.  Some of these problems might 
not have been related to the drug. 
 
 
 
Risks and side effects related to CC-5013 include: 
 
 
 
Low blood counts: low number of red blood cells, increased or decreased levels of white 
blood cells which help fight infection, low number of platelets which help the blood to 
clot, breakdown of red blood cells. 
 
 
 
Heart-related: abnormal heart rhythm, unusually fast or slow heartbeat, changes in your 
heart tracing (EKG), chest pain, high or low blood pressure, blockage of blood vessels 
decreasing the blood supply to the heart. A 15 year old girl getting CC-5013 had chest 
pain and a heart attack. This might have been related to the CC-5013. She recovered, but 
people can die from heart attacks.  
 
CC-5013 can cause blood clots in veins.  These clots could break off and block veins or 
arteries in other parts of the body, such as the heart or lungs.  Blood clots may be more 
likely in patients who are getting certain medicines like corticosteroids (prednisone, 
dexamethasone), interferon, erythropoietin (a medicine to make the red blood cells 
increase) or chemotherapy.  Patients who smoke or who do not move around very much 
may also be more likely to have blood clots.  If you have pain or swelling in an arm or 
leg, or feel chest pain or have trouble breathing, you should call your doctor right away.  
You might need to come to the hospital for more tests. 
 
 
 
Eye-related: dry eyes, blurred vision, visual flashing, disease of the retina. 
 
 
 
Stomach/Intestine-related:  bloated feeling, constipation (bowel movements that are 
difficult and less often than usual), diarrhea (watery bowel movements), dry mouth, 
difficulty swallowing, nausea (feeling as though you need to vomit), vomiting, stomach 
pain, pain in the gums, inflammation, dehydration, loss of appetite, excessive gas in the 
stomach, heartburn/indigestion, tearing of the colon, blockage in the intestine, gallbladder 
stones; irritation of the pancreas, the organ in the body that makes insulin. 
 
 

 
 
 
 
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 
General:  allergic reaction, sleepiness, fatigue, trouble sleeping, fever, weight loss, 
headache, general body pain; sweating, rigors/chills, infection, inflammation and 
swelling in the nose and sinus due to allergy and including sneezing, nasal stuffiness, and 
postnasal drip.  
 
 
 
Laboratory test-related:  abnormal liver or kidney function, abnormalities in the balance 
of salts in the blood (magnesium, calcium, potassium, sodium), high blood sugar, low 
testosterone (a male hormone), abnormal thyroid function, high cholesterol. 
 
 
 
Muscle/ Joint-related:  joint, muscle, or bone pain; back pain, muscle weakness, partial 
paralysis usually with loss of feeling on half of the body, arthritis, excessive buildup of 
fluids in the arms and legs. 
 
 
 
Nervous system-related:  difficulty speaking or writing,  difficulty understanding spoken 
or written words; feeling dizzy, confusion, change in the sense of taste;  , fainting spells, 
ringing in the ears, shaking, disease of the brain, blockage of blood vessels decreasing the 
blood supply to the brain, changes in your mental, motor, and sensory abilities, 
inflammation of the spinal cord, hallucinations/delusions, seizures, bleeding which may 
be life-threatening. 
 
 
 
Mood-related: depression, anxiety, agitation. 
 
 
 
Kidney-related:  bleeding, problems with urination, disease of the kidney, kidney failure.  
 
 
 
Breathing-related:  problems with your sinuses, cough, difficulty breathing, fluid build-up 
in the chest, bleeding which may be life-threatening, lung collapse 
 
 
 
Skin-related:  dry skin, severe itching, rash, hives, hair loss all over the body, pimples, a 
skin disease characterized by rash and bumps.  You may be more sensitive than usual to 
severe sunburn and should use sunblock or cover your skin if outside in the sun.  
 
 
 
Vein-related:  a disorder in which blood clots form throughout the body, problems with 
blood clotting. 
 
 
 
Tumor Lysis Syndrome: very rapid death of cancer cells releases chemicals which may 
lead to reduced kidney function.  Accumulation of these chemicals may harm muscle or 
nerve function. 
 
 
 
Reproductive Risks: If a person gets pregnant while receiving CC-5013, it could be 
dangerous for the baby. CC-5013 is related to thalidomide. If pregnant women take 
thalidomide, their babies can be born with no arms or legs. We do not know if CC-5013 
causes similar birth defects, but you should be sure not to get pregnant or father a baby 
while on this study. A pregnancy test will be done before each course of therapy for girls 
and women of childbearing age on this study. If at any time you think you might be 
pregnant, tell the study staff right away. You must not nurse (breast feed) a baby while on 
this study. You must NEVER donate blood or ova while on this study. CC-5013 does not 
cause abortion of the fetus and should never be used as a form of birth control.  Men must 
NOT be sperm or blood donors while taking CC-5013. 
 
 
 
 

 
 
 
 
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Lovastatin 
 
Common 
Serious 
Abdominal pain  
Constipation 
Diarrhea 
Nausea 
Headache 
Dermatomyositis 
Hepatotoxicity 
Drug-induced myopathy 
Myalgia 
Rhabdomyolysis 
Rupture of Tendon 
 
ADVERSE EFFECTS: Diarrhea is the most common reported adverse effect. Hyperkalemia, 
peripheral neuropathy, myopathy, myalgias, acute renal failure, rhabdomyolysis, elevated liver 
enzymes, hepatitis, behavioral changes, CNS depression also reported. One patient developed 
compartment syndrome resulting in a four-compartment fasciotomy from statin-induced myositis. 
 
• 
This drug may cause abdominal pain, constipation, diarrhea, nausea, or headache. 
• 
Instruct patient to report myalgias or signs/symptoms of myopathy or renal failure. 
• 
Patient should take tablets with evening meal and extended-release tablets at bedtime. 
• 
Advise patient there are multiple significant drug-drug interactions for this drug. Consult 
healthcare professional prior to new drug use (including over-the-counter and herbal 
drugs).  
• 
Patient should not drink large amounts of grapefruit juice (greater than 1 quart/day) while 
taking this drug. 
• 
Instruct patient to avoid alcohol during drug therapy. 
 
MEGESTROL ACETATE 
Brand Name(s): Megace 
Adverse Effects 
Serious:  
• 
Endocrine metabolic: Adrenal insufficiency 
• 
Hematologic: Anemia, Deep venous thrombosis, Thrombophlebitis 
• 
Respiratory: Pulmonary embolism 
 
Common: 
• 
Cardiovascular: Hypertension 
• 
Dermatologic: Rash, Sweating symptom 
• 
Endocrine metabolic: Hot sweats, Weight gain 
• 
Gastrointestinal: Diarrhea, Flatulence, Indigestion, Nausea, Vomiting 
• 
Neurologic: Insomnia 
• 
Psychiatric: Mood swings 
• 
Reproductive: Impotence 
 
Patient Information 
• 
This drug may cause sweating, hot flashes, weight gain, diarrhea, dyspepsia, flatulence, 
nausea, vomiting, insomnia, mood swings, impotence, anemia, deep venous thrombosis, 
thrombophlebitis, or pulmonary embolism. 
• 
Instruct patient to report signs/symptoms of adrenal insufficiency, as drug may suppress 
the hypothalamic-pituitary-adrenal axis. 

 
 
 
 
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• 
Inform patient that drug may need to be taken for at least 2 months before effectiveness 
can be determined. 
 
Contraindications 
• 
history of hypersensitivity to megestrol acetate or any component of the formulation 
• 
known or suspected pregnancy 
 
Precautions 
• 
diabetes 
• 
history of thromboembolic disease 
• 
megestrol acetate is not intended for prophylactic use to avoid weight loss 
• 
possibility of adrenal insufficiency in patients receiving or being withdrawn from chronic 
megestrol acetate therapy 
• 
use of megestrol in other types of neoplastic disease is not recommended 
 
 
Mercaptopurine 
 
Risks and side effects related to mercaptopurine include those which are: 
Likely 
Less Likely 
Rare But Serious 
• Fewer white blood 
cells, red blood cells 
and platelets in the 
blood 
○ 
A low number 
of red blood cells 
can make you feel 
tired and weak 
○ 
A low number 
of white blood 
cells can make it 
easier to get 
infections 
○ 
A low number 
of platelets cause 
you to bruise and 
bleed more easily 
• Loss of appetite 
• Nausea and/or vomiting 
• Diarrhea  
• Inflammation an/or sores in the mouth which 
may look like thrush  
• Red itchy rash and/or hives which may even 
occur a few weeks after treatment stops 
• Darkening of the skin (L) 
• Elevation in the blood of certain enzymes or 
bilirubin found in the liver which may mean 
liver irritation or damage 
• Hair loss 
• High levels of uric acid in the blood which 
could damage the kidneys 
• A feeling of extreme tiredness or weakness 
or not feeling well 
• Absence  or decrease in the number of  sperm  
which may decrease the ability to have 
children 
• Inflammation of the 
pancreas which can cause 
severe abdominal pain 
• Inflammation or scarring 
of the lungs which could 
lead to chest pain or 
discomfort and shortness 
of breath 
• Damage to the liver which 
can lead to inflammation 
and or scarring which 
could lead to a yellow 
appearing skin, and fluid 
collection in the stomach 
which makes it look larger 
• A new cancer or leukemia 
resulting from this 
treatment 
 
 
MESALAMINE 
Brand Name(s): Apriso  ;  Asacol  ;  Canasa  ;  Lialda  ;  Pentasa  ;  Rowasa  ;  sfRowasa 
Adverse Effects 
Serious:  
• 
Cardiovascular: Pericarditis (rare) 
• 
Gastrointestinal: Pancreatitis (less than 1%), Rectal hemorrhage (less than 3%) 
• 
Hematologic: Agranulocytosis (rare), Aplastic anemia (rare), Leukopenia (rare), 
Neutropenia (rare), Pancytopenia (rare), Thrombocytopenia (rare) 
• 
Hepatic: Cholestatic hepatitis (less than 3%), Hepatotoxicity (rare), Liver failure 

 
 
 
 
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• 
Immunologic: Hypersensitivity reaction 
• 
Renal: Renal impairment 
• 
Other: Drug intolerance, Syndrome 
 
Common: 
• 
Gastrointestinal: Abdominal pain (2.2% to 2.3%), Diarrhea (up to 8%), Flatulence (up to 
4%), Nausea (up to 4%), Ulcerative colitis (2.3% to 5.8%), Upper abdominal pain (1.2% 
to 5%) 
• 
Hepatic: Liver function tests abnormal (2.3%) 
• 
Neurologic: Headache (2.9% to 11%) 
• 
Respiratory: Nasopharyngitis (1.4% to 4%) 
 
Patient Information 
• 
Instruct patient to stop drug and report signs/symptoms of acute intolerance syndrome 
(cramping, acute abdominal pain, bloody diarrhea, fever, headache, or rash).  
• 
Warn patient with phenylketonuria that Apriso(TM) extended-release capsules contain 
aspartame.  
• 
Advise patient with sulfite sensitivity that Rowasa(R) enema contains metabisulfite.  
• 
Drug may cause abdominal pain, constipation, diarrhea, nausea, vomiting, arthralgia, 
asthenia, dizziness, or headaches.  
• 
Oral formulations may cause blood dyscrasias, especially in the elderly (65 years and 
older).  
• 
Advise patient to report signs/symptoms of renal failure (eg, nausea, vomiting, reduced 
urine output, drowsiness, headache, or back pain).  
• 
For rectal formulations, advise patient on proper administration technique and timing (use 
at bedtime) for maximum retention of drug.  
• 
Advise patient to avoid antacids with Apriso(TM) extended-release capsules.  
 
Contraindications 
• 
hypersensitivity to mesalamine, other salicylates (including aspirin), or to any component  
 
Precautions 
• 
acute intolerance syndrome, similar to exacerbation of inflammatory bowel disease or 
colitis, has been reported; discontinue treatment if this occurs  
• 
cardiac hypersensitivity reactions (myocarditis or pericarditis) have been reported; use 
cautiously in conditions predisposing patient to myocarditis or pericarditis (Lialda(R), 
rectal suspension, and enema)  
• 
concomitant use with antacids should be avoided (extended-release capsules 
(Apriso(TM))  
• 
concurrent oral products which contain or release mesalamine; increased risk of renal 
abnormalities (rectal suppositories and enema)  
• 
elderly (65 years and older); greater risk of blood dyscrasias; monitoring recommended 
(extended-release capsules and delayed-release tablets)  
• 
inflammatory bowel disease; exacerbation of symptoms including melena and 
hematochezia may occur (enema)  
• 
liver disease; hepatic failure has been reported (extended-release capsules and delayed-
release tablets)  
• 
pancolitis has been reported (rectal suppositories and enema)  
• 
phenylketonuria; contains aspartame (extended-release capsule)  

 
 
 
 
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• 
pyloric stenosis; possibility of prolonged gastric retention of mesalamine (delayed-release 
tablets)  
• 
renal dysfunction or history of renal disease; increased risk of renal toxicity; monitoring 
recommended  
• 
renal impairment, including minimal change nephropathy, acute and chronic interstitial 
nephritis, and rarely renal failure have been reported; increased risk in those with renal 
disease; monitoring recommended  
• 
sulfasalazine hypersensitivity, history; possibility of similar hypersensitivity reaction  
• 
sulfite hypersensitivity; contains metabisulfite (enema)  
• 
report suspected adverse reactions to the US Food and Drug Administration at 1-800-
FDA-1088 or www.fda.gov/medwatch  
 
 
 
Metformin 
 
Common 
Serious 
Cobalamin deficiency 
Diarrhea 
Flatulence 
Indigestion 
Nausea 
Vomitting 
Asthenia 
Lactic acidosis (generally associated with 
underlying conditions such as renal 
insufficiency, hepatic disease, sepsis, etc) 
 
• 
Drug may cause diarrhea, dyspepsia, flatulence, nausea, vomiting, hyper- or 
hypoglycemia, or asthenia.  
• 
Instruct patient to report signs/symptoms of lactic acidosis (nausea, vomiting, abdominal 
pain, tachypnea). Elderly patients (80 years and older) are at increased risk.  
• 
Patient should take tablets with meals and extended-release tablets with the evening meal.  
• 
Tell patient to maintain adequate hydration to prevent renal dysfunction.  
• 
Tell patients to notify healthcare provider of metformin use before having radiologic 
studies using IV dye.  
• 
Patient should not drink alcohol while taking this drug.  
 
Methimazole 
 
Common 
Serious 
Skin rash 
Uriticaria 
Nausesa 
Vomiting 
Epigastric distress 
Arthralgia 
Paresthesia 
Loss of taste 
Agranulocytosis 
Aplastic anemia 
Hepatotoxicity 
Drug fever 
Lupus-like syndrome 
Insulin autoimmune syndrome 
Periartheritis 
Hypoprothrombinemia 

 
 
 
 
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Abnormal loss of hair 
Myalgia 
Headache 
Pruritus 
Drowsiness 
Neuritis 
Edema 
Vertigo 
Skin pigmentation 
Jaundice 
Sialadenopathy 
Lymphadenopathy 
Nephritis (very rarely) 
Advise patient to report signs/symptoms of hepatotoxicity, aplastic anemia, or infection (fever, 
headache, malaise, skin eruptions, sore throat). 
Methotrexate 
Risks and side effects related to methotrexate (when given by mouth or vein) include those which 
are: 
 
Likely 
Less Likely 
Rare But Serious 
• High levels of liver 
enzymes in the 
blood which may 
mean liver irritation 
or damage 
• Nausea 
• Vomiting 
• Loss of appetite 
• Diarrhea 
• Chills and/or fever 
• Inflammation and/or sores in the 
mouth, gums, throat and/or 
esophagus 
• Inflammation of the intestines 
which may cause bleeding 
• Sensitivity to sunlight and 
increased risk of sunburn 
• Fewer white blood cells, red 
blood cells and platelets in the 
blood. 
○ 
A low number of red blood 
cells can make you feel tired 
and weak. 
○ 
A low number of white 
blood cells can make it easier 
to get infections. 
○ 
A low number of platelets 
causes you to bruise and bleed 
• Learning disability 
• Dizziness 
• Sense of not feeling well or 
tiredness 
• Drowsiness 
• Blurred vision 
• Rashes with itching and hives 
• Hair loss, inflammation of the 
• Severe allergic reaction which can be 
life threatening with shortness of 
breath, low blood pressure and a rapid 
heart rate 
• The rapid death of large numbers of 
tumor cells which can cause the 
potassium and phosphate salts and the 
uric acid in the blood to rise quickly 
and this could lead to a life-threatening 
irregular heart beat or damage to the 
kidneys.  
• Severe rashes which can cause loss of 
skin or damage to mucous membranes 
or which can cause peeling, redness 
and pain on the palms of the hands and 
soles of the feet  
• Damage, inflammation and/or scarring 
of lung tissue which may make you 
short of breath and cough 
• Seizures 
• Temporary damage to the brain such 
that you may experience headaches, 
drowsiness, difficulty speaking or 
forming words, blurred vision or 
temporary blindness, and decreased 
reflexes 
• Temporary loss of function or feeling 
in the lower part of the body (partial 
paralysis) 
• Severe damage to brain tissue which 
over time could lead to difficulty 
carrying out normal daily tasks or 

 
 
 
 
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hair follicles 
• Acne 
• Tearing and inflammation of the 
eyes 
• Darkening of the fingernails  
could lead to a coma. 
• Inflammation and scarring of  the liver  
• Damage to the bone which could lead 
to arthritis pain and weakness of the 
bone 
• Inflammation of the heart 
• Fluid buildup around the heart 
• Damage to the kidney  
 
 
 
 
 
 
Methyl CCNU 
 
ADVERSE REACTIONS (Reported to be the same as BiCNU) Need to change drug name 
as listed below 
Common 
Serious 
Nausea 
Vomiting 
Burning at injection site 
Suffusion of the conjunctiva 
Chest pain 
Headache 
Pulmonary infiltrates (late effect) 
Pulmonary fibrosis (late effect) 
Delayed myelosuppression 
Delayed leucopenia 
Delayed thrombocytopenia 
Anemia 
Neutropenia 
Hepatic toxicity 
Renal damage 
Nephrotoxicity 
Decreased kidney size 
Renal failure 
Allergic reaction 
Neuroretinitis 
Hypotention 
tachycardia 
 
 
Minocycline 
Risks and Discomforts 
If you agree to enroll in this study, there may be some risks to your health and well-being.  
Known side effects associated with minocycline use are: sensitivity to sunlight (frequent; greater 
than 20%); dizziness; constipation; nausea; vomiting; and loss of appetite (occasional; 2 to 20%).  
To avoid sunlight sensitivity, you can use sunscreen, wear clothing with long sleeves and long 
pants, and try to stay out of direct sun as much as possible.  In rare cases (less than 2%), staining 
of the outer layer of teeth, kidney disease, anemia (low iron and red blood cells which may cause 
tiredness and shortness of breath), and liver disease have been reported.   
 
Rare instances of inflammation of the esophagus (or food pipe) and ulcers in the esophagus have 
also been reported with minocycline.  To reduce the risk of irritation of the esophagus, your study 
medication, if taken by mouth, should be taken with a full glass of water (8 ounces).  If you 

 
 
 
 
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experience pain when swallowing, you must report this to your study doctor immediately. The 
study medication can be taken with or without food. 
 
Other side effects of minocycline include rash, hives, headache, joint pain, and allergic reactions 
(rare; 1-3%). 
 
Serious allergic reactions that can be life-threatening may occur with minocycline use. 
 
You should be very careful when driving or using machinery until you know how the study 
drug(s) will affect you.  This is because the study medication(s) may cause drowsiness, dizziness, 
lack of coordination, or slow your reaction time. 
 
There may be other risks which are not known at this time and which we cannot predict. 
 
Minocycline may not be as effective if taken with any antacids, calcium supplements, iron 
products, and laxatives containing magnesium. None of these medications may be taken within 2 
hours before or after taking Minocycline. 
In addition, minocycline may interfere with the effectiveness of oral contraceptives.  Therefore, 
for female subjects of childbearing potential, the addition of a barrier method of contraception 
(condom or diaphragm) will be required during the study.  Minocycline may be dangerous to an 
unborn child (fetus or embryo). If, at any time during the study, you suspect that you are 
pregnant, you must immediately notify your study doctor.  
 
 
MITOXANTRONE 
 
 
Common 
Happens to 21-100  
children out of every 
100 
Occasional 
Happens to 5-20 
children out of every 
100 
Rare 
Happens to < 5 
children out of every 
100 
Immediate: 
Within 1-2 days of 
receiving drug 
 
Nausea, vomiting, 
diarrhea, fever, 
anorexia, green blue 
discoloration of the 
urine and/or sclera 
 
Abdominal pain, back 
pain, headache, 
phlebitis, 
constipation 
Anaphylaxis, 
angioedema, 
cardiac arrhythmias1 
(bradycardia), 
seizures, 
extravasation 
reactions rare but if 
occur can lead to: 
(erythema, swelling, 
pain, burning and/or 
blue 
discoloration of the 
skin 
and rarely tissue 
necrosis), 
tumor lysis 
Prompt: 
Within 2-3 weeks, 
prior to 
the next course 
Myelosuppression (L), 
mucositis /stomatitis, 
immunosuppression, 
alopecia, fatigue 
Transient elevation of 
LFTs, pruritis with 
desquamation of the 
skin due to 
progressive dryness 
Rash, conjunctivitis, 
(GI) 
hemorrhage, 
interstitial 
pneumonitis 

 
 
 
 
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Delayed: 
Any time later during 
therapy 
Amenorrhea, menstrual 
disorders, temporary 
reduction in sperm 
count 
Cardiotoxicity 
(decreased 
LVEF)2 (L) 
CHF, hepatotoxicity 
Late: 
Any time after 
completion 
of treatment 
 
 
 
Secondary 
malignancy 
Unknown 
Frequency and 
Timing: 
 
Fetal toxicities and teratogenic effects of mitoxantrone have been noted 
in animals. 
Toxicities include: low birth weight and prematurity. Mitoxantrone is 
excreted in 
human milk and significant concentrations (18 ng/mL) have been 
reported for 28 days 
after the last administration. 
1 Rarely clinically significant. 
2 Risk increases with chest radiation and prior anthracycline dosage 
(L) Toxicity may also occur later. 
 
 
Nabumetone 
 
Common 
Serious 
Edema 
Pruritus 
Skin Rash 
Abdominal pain 
Constipation 
Diarrhea 
Flatulence 
Indigestion 
Nausea 
Occult blood in stools 
Dizziness 
Headache 
Insomnia 
tinnitus 
Hypertension 
Myocardial infarction (<2%) 
Thrombotic tendency observation 
Erythema multiforme (rare) 
Scaling eczema 
Stevens-Johnson syndrome 
Toxic epidermal necrolysis (<0.1%) 
Gastrointestinal hemorrhage (<1%) 
Gastrointestinal perforation (<1%) 
Inflammatory disorder of digestive tract 
Melena (<1%) 
Anemia 
Thrombocytopenia (<1%) 
Hepatitis 
Increased liver function test (up to 15%) 
Jaundice 
Liver failure (rare) 
Immune Hypersensitivitiy reaction (<1%) 
Cerebrovascular accident 
Albuminuria (<1%) 
Interstitial nephritis (rare) 
Renal azotemia (<1%) 
Renal failure (rare) 
Bronchospasm (<2%) 
 

 
 
 
 
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• 
Advise patient to immediately report signs/symptoms of Stevens-Johnson syndrome (flu-
like symptoms, spreading red rash, or skin/mucous membrane blistering). 
• 
Patients with a cardiac history or on a long-term regimen are at an increased risk for 
adverse cardiovascular thrombotic events. Advise patient to report signs/symptoms of 
myocardial infarction or stroke. 
• 
Instruct patients to report signs/symptoms of serious gastrointestinal events such as 
bleeding, ulceration, or perforation of stomach or intestines. Tell patient drug is best 
taken with food or milk. 
• 
Patient should not drink alcohol while taking this drug. 
• 
Advise patient to avoid concomitant use of oral corticosteroids, as this may increase the 
risk for serious gastrointestinal effects. 
NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial 
infarction, and stroke, which can be fatal. This risk may be increased in patients with 
cardiovascular disease or risk factors for cardiovascular disease. Nabumetone is contraindicated 
for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) 
surgery. NSAIDs can also cause an increased risk of serious gastrointestinal adverse events 
especially in the elderly, including bleeding, ulceration, and perforation of the stomach or 
intestines, which can be fatal. 
 
 
Naproxen 
 
Common (>3 %) 
Serious (1-3%) 
Rare (<1%) 
Edema 
Pruritus 
Skin Rash 
Abdominal Pain 
Constipation 
Diarrhea 
Heartburn 
Indigestion 
Nausea 
Stomatitis 
Dizziness 
Headache 
Somnolence 
Tinnitus 
Dyspnea 
Lightheadedness 
Vertigo 
Scaling eczema 
Inflammatory disorder of digestive 
tract 
Anemia 
Thrombotic tendency observations 
Increased liver function 
Congestive Heart Failure 
Myocardial Infarction 
Pulmonary Edema 
Vasculitis 
Steven-Johnson syndrome 
Toxic epidermal necrolysis 
Gastrointestinal hemorrhage 
Gastrointestinal perforation 
Pancreatitis 
Agranulocytosis 
Granulocytopenic disorder 
Thrombocytopenia 
Hepatitis 
Jaundice 
Liver failure 
Anaphylactoid reaction 
Aspectic meningitis 
Cerebrovascular accident 
Seizure 
Interstitial nephritis 
Nephrotic syndrome 
Papillary necrosis 
Renal failure 
Serum creatinine raised 
 

 
 
 
 
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• 
Patient should avoid activities requiring mental alertness or coordination until drug 
effects are realized, as drug may cause dizziness or somnolence. 
• 
This drug may cause edema, abdominal pain, constipation, diarrhea, dyspepsia, 
heartburn, nausea, stomatitis, anemia, headache, tinnitus, dyspnea, scaling eczema, or 
liver failure. 
• 
Patients with a cardiac history or on a long-term regimen are at an increased risk for 
adverse cardiovascular thrombotic events. Advise patient to report signs/symptoms of 
myocardial infarction or stroke. 
• 
Instruct patients to report signs/symptoms of serious gastrointestinal events such as 
bleeding, ulceration, or perforation of stomach or intestines. Elderly and debilitated 
patients may be at an increased risk for this adverse effect. 
• 
Tell patient drug is best taken with food or milk. 
• 
Patient should not drink alcohol while taking this drug. 
NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial 
infarction, and stroke, which can be fatal. This risk may be increased in patients with 
cardiovascular disease or risk factors for cardiovascular disease. Naproxen is contraindicated for 
the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) 
surgery. NSAIDs can also cause an increased risk of serious gastrointestinal adverse events 
especially in the elderly, including bleeding, ulceration, and perforation of the stomach or 
intestines, which can be fatal. 
 
 
VINORELBINE TARTRATE 
Brand Name(s): Navelbine 
Adverse Effects 
Serious:  
• 
Cardiovascular: Non-ST segment elevation myocardial infarction, acute 
• 
Gastrointestinal: Bowel obstruction, Constipation, Pancreatitis, Paralytic ileus, 
Perforation of intestine 
• 
Hematologic: Granulocytopenic disorder (Severe), Significantly greater in combination 
with cisplatin, Myelosuppression, Significantly greater in combination with cisplatin 
• 
Hepatic: AST/SGOT level raised (frequent) 
• 
Respiratory: Acute respiratory distress syndrome, Bronchospasm, Interstitial lung 
disease 
• 
Other: Sepsis 
 
Common: 
• 
Dermatologic: Alopecia (grades 1 and 2, up to 35%; grades 3 and 4, 4% to 12%), 
Injection site reaction 
• 
Gastrointestinal: Diarrhea, Nausea, Vomiting 
• 
Neurologic: Asthenia, Neuromyopathy 
 
Patient Information 
• 
Advise patient to avoid vaccines during therapy due to drug-induced immunosuppression. 
• 
This drug may cause alopecia, tissue necrosis, diarrhea, nausea, vomiting, constipation, 
asthenia, and neuromyopathy. 
• 
Drug may also cause significant adverse effects including bowel obstruction, pancreatitis, 
paralytic ileus, and perforation of intestine. 
• 
Instruct patient to report signs/symptoms of myelosuppression. 

 
 
 
 
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• 
Advise patient to report signs/symptoms of respiratory adverse effects such as acute 
respiratory distress syndrome, bronchospasm, and dyspnea. 
 
Contraindications 
• 
granulocytopenia, granulocyte counts less than 1,000 cells/mm(3); withhold 
administration  
• 
intrathecal administration; can be fatal  
 
Precautions 
• 
extravasation causing local tissue necrosis and/or thrombophlebitis can occur  
• 
granulocytopenia, granulocyte counts from 1,000 to 1,499 cells/mm(3); dose adjustments 
according to complete blood counts with differentials obtained on the day of treatment  
• 
compromised bone marrow reserve 
• 
concomitant mitomycin, cisplatin, CYP3A inhibitors 
• 
concomitant or sequential treatment with paclitaxel 
• 
prior history or pre-existing neuropathy 
• 
prior radiation therapy- radiation recall 
• 
severe hepatic injury or impairment 
• 
use proper procedures for handling and disposal of chemotherapy 
 
 
Nitisinone 
  Adverse Events 
Common ≥ 1% 
Rare < 1% 
Exfoliative Dermatitis 
Dry Skin 
Cutaneous pruritus 
Alopecia 
Maculopapular rashes 
Leukopenia 
Thrombocytopenia 
Conjunctivitis 
Corneal opacity 
Keratitis 
Light sensitivity 
Diarrhea 
Abdominal pin 
Gastroenteritis 
Gastrointestinal hemorrhage  
Liver failure 
Neoplasm of liver 
• 
Patient should report development of a rash or signs/symptoms of leukopenia, 
thrombocytopenia, or hepatic failure. 
• 
Advise patient to report ocular symptoms (photophobia, eye pain, burning, redness, or 
swelling). 
• 
Patient should take drug on an empty stomach at least 1 h before a meal. 
• 
Instruct patient on any dietary tyrosine restrictions. Foods high in tyrosine include dairy 
products, meat, fish, eggs, pumpkin or sesame seeds, almonds, avocados, and soy. 
 
 
 
 
 

 
 
 
 
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Omeprazole 
Common ≥ 1% 
Rare < 1% 
Abdominal pain (2.4% to 5.4%), Diarrhea (3% 
to 3.7%) 
Diarrhea (3% to 3.7%) 
Constipation (1.1% to 1.5%) 
Flatulence (2.7%) 
Nausea (2.2% to 4%) 
Vomiting (1.5% to 3.2%)  
Headache (2.9% to 6.9%) 
Back pain (1.1%) 
Asthenia (1.2%) 
Dizziness (1.5%)  
Cough (1.1%) 
Pancreatitis 
Hepatotoxicity 
Bone fracture 
Joint pain 
Muscle cramps 
Osteroporosis-related bone fracture 
Hip fracture 
Rhabdomyolysis 
Myalgia 
Myositis 
Leg pain 
Throat pain 
Interstital nephrisis 
Visual disturbances 
Ringing in the ear 
Urinary Tract infection 
Epistaxis 
• 
This drug may cause constipation, diarrhea, nausea, and headache. 
• 
Tell patients on long-term therapy to report signs/symptoms of atrophic gastritis. 
• 
Advise patient to take drug before a meal. 
Orlistat 
 
Common ≥ 5% 
Rare < 1% 
Abdominal discomfort 
Abdominal pain 
Defecation urgency 
Increased frequency of defecation 
Steatorrhea 
Cholelithiasis (2.9) 
• 
This drug may cause abdominal discomfort or pain, urgency or increased frequency of 
defecation, and steatorrhea. 
• 
If using concurrently with orlistat, patient should take multivitamins or cyclosporine at 
least 2 h before or 2 h after an orlistat dose. 
• 
Advise patient to take this drug during or up to 1 h after meals containing fat. Patient 
should omit dose if a meal is missed or contains no fat. 
• 
Instruct patient to take a missed dose as soon as possible up to 1 h after meal. If missed 
dose is more than 1 h overdue, skip the missed dose. 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Oxaliplatin 
 
Risks and side effects related to oxaliplatin include those which are: 
 
Likely 
• 
Numbness or tingling sensation of mouth, throat, arms, legs, fingers and toes 
which may become worse with cold temperatures and which may affect the 
ability to perform tasks that require fine muscle coordination   
• 
Nausea and vomiting 
• 
Stomach cramps or pain 
• 
Diarrhea or constipation 
 
 Less Likely   
• 
Headache 
• 
Runny nose  
• 
Feeling of “heartburn”   
• 
Change in taste 
• 
Dehydration (fluid loss) 
• 
Dizziness and/or loss of coordination 
• 
Feeling of extreme tiredness not relieved by rest or sleep 
• 
Reddening and cracking of the skin on the hand palms and soles of the feet, 
associated with pain and possibly infection 
• 
Sudden reddening of face and neck 
• 
Rash 
• 
Difficulty sleeping  
• 
Loss of appetite or desire to eat 
• 
Allergic reaction that may be life threatening 
• 
Shaking chills 
• 
Blood in the urine 
• 
Painful or difficulty urinating  
• 
Inflammation of the vein through which the drug was given 
• 
Fewer white blood cells, red blood cells and platelets in the blood* 
o A low number of white blood cells can make it easier to get infections 
o A low number of red blood cells can make you feel tired and weak 
o A low number of platelets causes you to bruise and bleed more easily 
• 
Nose bleed  
• 
Loss of weight 
• 
Soreness or ulcers inside the mouth and throat 
• 
Hair loss 
• 
Swelling of the hands, arms, feet and legs 
• 
Joint pain 
• 
Lung infections 
• 
Sore throat 
• 
Fever  
• 
Increased levels of creatinine in the blood which could mean kidney damage  
• 
Lower levels of a salt (potassium) which is measured in the blood 
• 
Too much acid in the blood 
• 
Hiccups 
• 
Too much gas produced in the intestines 
 

 
 
 
 
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• 
Difficulty swallowing 
• 
Mild increases in liver enzymes without symptoms and usually returning to 
normal 
• 
Increase in blood pressure 
• 
Inflammation of the ear 
• 
Inflammation of the small bowel which may cause pain and discomfort 
• 
A feeling of depression 
• 
Cough 
• 
Bone Pain 
• 
Inability to urinate 
• 
Damage to the surface of the eye which might lead to pain and tearing 
• 
Restless movements that are not under your control (involuntary) 
 
Rare but some of these can be serious 
• 
Shortness of breath  
• 
Sudden, temporary feeling of difficulty in swallowing or breathing which can 
occur during or shortly after the infusion and may be caused by swallowing a 
cold drink 
• 
Infections 
• 
Irregular or rapid heart beat 
• 
Rare but serious damage to the liver which can lead to an enlarged liver and 
spleen, bleeding from the veins in the esophagus, a yellow appearing skin, and 
fluid collection in the abdomen which makes your abdomen look larger 
• 
Tissue irritation or damage which may be severe if drug leaks from the injection 
site – this may cause pain, redness and swelling 
• 
Severe allergic reaction which can be life threatening  with shortness of breath, 
low blood pressure and a rapid heart rate 
• 
Blood clots 
• 
Blurred vision or blind spots in vision 
• 
Damage to lung tissue 
• 
Damage to kidney which may be permanent 
• 
Loss of some hearing 
• 
A bleeding disorder that can cause bleeding from many areas of the body 
including the nose, the rectum and the urine 
• 
A blockage of the intestine that may require treatment    
• 
Inflammation of the pancreas which can cause severe abdominal pain 
 
 
 
Oxaprozin 
 
Common ≥ 1% 
Rare < 1% 
%) Rash 
Abdominal pain 
Constipation 
Diarrhea 
Indigestion 
Nausea 
Vomittin 
Tinnitus 
Edema 
Hypertension 
Palpitations 
Thrombotic tendency observations 
Erythema multiforme 
Scaling eczema 
Stevens-Johnson Syndrome 
Toxic epidermal necrolysis 
 

 
 
 
 
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Dysuria 
Increased frequency of urination 
Myocardial infaraction 
Cerebrovascular accident 
Gastrointestingal hemorrhage 
Gastrointestinal perforation 
Inflammatory disorder of digestive tract 
Pancreatitis 
Agranulocytosis 
Anemia 
Leucopenia 
Thrombocytopenia 
Hepatitis 
Increased liver function test 
Jaundice 
Liver failure 
Anaphylactoid reaction 
Amblyopia 
Hearing loss 
Acute renal failure 
Hematuria 
Interstitial nephritis 
Bronchospasm  
Serum sickness due to drug 
      
 
• 
This drug may cause abdominal pain, constipation, diarrhea, dyspepsia, nausea, vomiting, 
tinnitus, dysuria, photosensitivity, increased urinary frequency, or bronchospasm. 
• 
Advise patient to report signs/symptoms of serious cardiovascular thrombotic events, 
myocardial infarction, and stroke. 
• 
Patient should also report signs/symptoms of bleeding, ulceration, or perforation of the 
stomach or intestines. Elderly and debilitated patients are at higher risk while taking this 
drug. 
• 
Tell patient to avoid concurrent use of other NSAIDs unless approved by healthcare 
professional. 
NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial 
infarction, and stroke, which can be fatal. This risk may be increased in patients with 
cardiovascular disease or risk factors for cardiovascular disease. Oxaprozin is contraindicated for 
the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) 
surgery. NSAIDs can also cause an increased risk of serious gastrointestinal adverse events 
especially in the elderly, including bleeding, ulceration, and perforation of the stomach or 
intestines, which can be fatal. 
 
Paclitaxel 
 
Risks and side effects related to Paclitaxel include those which are: 
 
Likely 
Less Likely 
Rare but serious 
• 
Nausea 
• 
Reddening of the face or 
skin with feelings of 
• Vomiting 
• Diarrhea 
• Shortness of breath 
• 
Severe allergic reaction 
which can be life 
threatening with shortness 

 
 
 
 
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warmth 
• 
Temporary changes on a 
test called an EKG that 
measures the activity of 
your heart 
• 
A feeling of weakness 
and/or tiredness 
• 
Aches and pains in the 
muscles or joints 
• 
Loss of appetite 
• 
Temporary hair loss 
• 
Fewer white blood cells 
and red blood cells in the 
blood  
o a low number of white 
blood cells can make 
it easier to get 
infections 
o a low number of red 
blood cells can make 
you feel tired and 
weak 
• 
A problem in nerve 
function that may cause 
pain, numbness, tingling, 
and muscle weakness in 
various parts of the body 
• 
Inflammation and/or sores 
in the mouth (and/or throat 
and /or esophagus, the 
tube that leads from the 
mouth to the stomach) that 
may make swallowing 
difficult and are painful 
(painful mouth sores) 
• 
Elevation in the blood of 
certain enzymes or 
chemicals found in the 
liver which might  indicate 
liver irritation or damage 
 
 
• Fluid retention and build-
up in the tissues usually of 
the lower legs leading to an 
increase in weight 
• Cough 
• Rash with itching or hives 
• Low or high blood pressure 
• Fainting 
• Infections including those 
caused by bacteria, virus, 
and fungus 
• Elevation in the blood of 
bilirubin (a substance that 
comes from the liver 
breaking down waste 
products)  found in the 
liver  
•  found in the liver  
• Fewer platelets in the blood  
o a low number of 
platelets causes you to 
bruise and bleed more 
easily 
• Back or chest pain 
• Pain, redness, 
inflammation and skin 
damage in the vein through 
which the drug was given   
• Fever with a low white 
blood cell count which 
could indicate infection 
and may require 
hospitalization and 
treatment with antibiotics 
• Unsteadiness when 
walking 
• Inflammation, pain and 
reddening of the eye with 
watery eyes 
• Inflammation of the nerves 
to the eye which could lead 
to blurred vision or other 
vision changes 
• Damage to the ear causing 
hearing loss, which maybe 
temporary or permanent, 
balance problems 
(dizziness) and ringing in 
the ears 
• The finger or toe nails may 
darken in color 
of breath, low blood 
pressure, rapid heart rate, 
chest pain, chills and 
fever  
• 
Severe allergic reaction 
which can be life 
threatening with rapid 
build-up of fluid under the 
skin, in the lining of the 
intestine and possibly in 
the throat or swelling of 
the tongue which could 
make it difficult to breath.   
• 
Clotting of blood vessels 
which can lead to pain 
and swelling in the area of 
the clot. Such clots make 
break loose and cause 
damage or be life-
threatening depending on 
where they go. 
• 
Abnormal heart rate 
which may be life-
threatening 
• 
Heart attack 
• 
Bleeding which can occur 
in the head, stools, the 
nose, urine and other parts 
of the body 
• 
Seizures 
• 
Severe damage to the 
brain which may lead to 
difficulty carrying out 
normal daily tasks and to 
coma 
• 
A stoppage (or blockage) 
of the intestine which may 
require treatment 
• 
Severe rashes which can 
result in loss of skin and 
damage to mucous 
membranes and which 
may be life-threatening 
• 
Damage to the heart 
muscle which may make 
you tired, weak, feel short 
of breath, and retain fluid 
• 
Inflammation, infection or 
scarring of the lungs that 
can lead to fluid in the 
lungs and affect your 

 
 
 
 
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• Chills  
 
ability to breathe and the 
levels of oxygen in your 
blood making you short of 
breath 
• 
Damage to the liver which 
can lead to inflammation 
and/or scarring which 
could lead to a yellow 
appearing skin, and fluid 
collection in the abdomen 
(belly) which makes it 
look larger 
 
 
 
PAMIDRONATE DISODIUM 
Brand Name(s): Aredia 
Adverse Effects 
Serious:  
• 
Musculoskeletal: Arthralgia (13.6%), Aseptic necrosis of bone of jaw, Bone pain (at 
least 10% to 15%), Myalgia (26%) 
• 
Neurologic: Seizure (2%) 
• 
Renal: Focal segmental glomerulosclerosis 
 
Common: 
• 
Dermatologic: Injection site reaction 
• 
Endocrine metabolic: Hypocalcemia (12%), Hypokalemia (18%), Hypomagnesemia 
(12%), Hypophosphatemia (18%) 
• 
Gastrointestinal: Loss of appetite, Nausea, Vomiting 
• 
Hematologic: Anemia (42.5%) 
• 
Renal: Urinary tract infectious disease (18.5%) 
• 
Other: Fever 
 
Patient Information 
• 
This drug may cause anorexia, nausea, vomiting, or fever. 
• 
Advise patient to report incapacitating or severe bone, joint, and/or muscle pain . 
• 
Patient should report signs/symptoms of renal impairment or anemia. 
• 
Tell patients with concomitant risk factors for osteonecrosis of the jaw to report 
signs/symptoms of this condition (gum loss, numbness, or pain, swelling, infection of 
jaw/gums). Risk factors for osteonecrosis of the jaw include cancer, chemotherapy, 
corticosteroids, or poor oral hygiene. 
 
Contraindications 
• 
hypersensitivity to pamidronate or other bisphosphonates 
 
Precautions 
• 
anemia, leukopenia, or thrombocytopenia, preexisting; monitoring recommended  
• 
focal segmental glomerulosclerosis (including the collapsing variant); has been reported, 
especially when treating multiple myeloma and breast cancer  

 
 
 
 
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• 
metabolic abnormalities (eg, calcium, phospate, magnesium, potassium levels) may 
occur; monitoring recommended  
• 
musculoskeletal pain, severe; has been reported within days, months, or years following 
therapy initiation; consider discontinuing bisphosphonates if symptoms occur  
• 
osteonecrosis of the jaw has been reported; risk factors include: cancer (advanced breast 
cancer, multiple myeloma), chemotherapy, corticosteroids, local infections, and dental 
status (dental extraction, periodontal disease, local trauma including poor fitting 
dentures); a dental examination with appropriate preventive dentistry should be 
considered prior to bisphosphonate treatment; invasive dental procedures should be 
avoided during bisphosphonate treatment  
• 
renal function deterioration, progression to renal failure, and dialysis have been reported 
following initial or single doses; patients with multiple myeloma also receiving thalidomide 
may be at increased risk; single doses should not exceed 90 mg; monitoring 
recommended; withhold therapy for renal deterioration in patients with bone metastases  
• 
renal impairment, preexisting; increased risk of renal adverse events; monitoring 
recommended; treatment of bone metastases in severe impairment is not recommended  
• 
thyroid surgery, history of; may predispose to hypoparathyroidism and increase risk of 
hypocalcemia  
 
 
 
 
Pazopanib  
 
Risks and side effects related to the pazopanib include the following: 
 
Likely:   
• Lack of enough red blood cells (anemia) 
• Diarrhea 
• Nausea or the urge to vomit 
• Fatigue or tiredness 
• Increased blood level of a liver enzyme (ALT/SGPT) 
• Increased blood level of a liver enzyme (AST/SGOT) 
• Increased blood level of a liver pigment (bilirubin) often a sign of liver 
problems 
• Decreased number of a type of white blood cell (lymphocyte) 
• Decreased number of a type of white blood cell (neutrophil/granulocyte) 
• Decrease in the total number of white blood cells (leukocytes) 
• Increased blood sugar level 
• Changes in hair color 
• High blood pressure  
 
Less Likely: 
• Belly pain 
• Constipation 
• Vomiting 
• Test that shows a problem in blood clotting 
• Increased blood level of a liver or bone enzyme (alkaline phosphatase) 

 
 
 
 
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• Increased blood level of creatinine (a substance normally eliminated by the 
kidneys into the urine) 
• Increased INR (measure of the ability of the blood to clot properly) which 
increases the risk of bleeding 
• Increased blood level of fat-digesting enzyme (lipase) 
• Decreased number of a type of blood cell that helps to clot blood (platelet) 
• Increased blood level of a digestive enzyme level (amylase) 
• Loss of appetite 
• Dehydration (when your body does not have as much water and fluid as it 
should) 
• Increased blood level of potassium 
• Increased blood level of magnesium 
• Increased blood level of sodium  
• Decreased blood level of calcium 
• Decreased blood sugar level 
• Decreased blood level of potassium  
• Decreased blood level of magnesium 
• Decreased blood level of sodium  
• Decreased blood level of phosphate 
• Joint pain 
• Back pain 
• Dizziness (or sensation of lightheadedness, unsteadiness, or giddiness) 
• Taste changes 
• Headache or head pain 
• More protein leaking into the urine than usual, often a sign of kidney disease 
• Bleeding in some organ(s) of the respiratory tract  
• Hair loss 
• Skin rash with the presence of macules (flat discolored area) and papules 
(raised bump) 
• Lightening of the skin 
 
Rare but Serious: 
• Decrease in heart's ability to pump blood during the "active" phase of the 
heartbeat (systole) 
• Heart attack caused by a blockage or decreased blood supply to the heart 
• Gastrointestinal fistula: Abnormal hole between an organ of the digestive 
tract and another organ or tissue  
• Bleeding in some organ(s) of the digestive tract 
• Gastrointestinal perforation: A tear or hole in the stomach or gut that can 
lead to serious complications and may require surgery to repair  
• Abnormal electrical conduction within the heart that may result in sudden 
death 
• Abnormal changes in the brain that can cause a collection of symptoms 
including headache, confusion, seizures, and vision loss associated with MRI 
imaging findings (RPLS) 

 
 
 
 
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• Abnormal hole between part of the urinary system and another organ or 
tissue 
• Abnormal hole between a female reproductive organ and another organ 
• Abnormal hole between the uterus (womb) and another organ 
• Abnormal hole between the vagina and another organ or tissue 
• Swelling and redness of the skin on the palms of the hands and soles of the 
feet 
• Formation of a blood clot in a vein that breaks loose and is carried by the 
blood stream to plug another blood vessel 
• Formation of a blood clot in an artery that breaks loose and is carried by the 
blood stream to plug another blood vessel 
• Bleeding into the tumor or organs which may be life threatening 
 
Reproductive risks:  You should not become pregnant or father a baby while on this 
study because the drugs in this study can affect an unborn baby.  Women should not 
breastfeed a baby while on this study.  It is important you understand that you need 
to use birth control while on this study.  Check with your study doctor about what kind 
of birth control methods to use and how long to use them.  Some methods might not be 
approved for use in this study. The effect of pazopanib on your ability to have children in 
the future is unknown. 
 
We will tell you if we learn any new information that may affect your health, welfare, or 
decision to stay in this study.  
 
 
 
 
Peg-asparaginase  
 
 
 
Common 
Happens to 21-100  
children out of every 
100 
Occasional 
Happens to 5-20 
children out of every 
100 
Rare 
Happens to < 5 
children out of every 
100 
Immediate: 
Within 1-2 days of 
receiving drug 
 
Allergic reactions (total 
likelihood of local, and or 
systemic reaction 
especially if previous 
hypersensitivity reaction to 
native asparaginase), pain 
at injection site, weakness, 
fatigue, diarrhea  
Allergic reactions (total 
likelihood of local, and or 
systemic reaction if no 
previous hypersensitivity 
reaction to native 
asparaginase), rash  
Anaphylaxis, 
hyper/hypotension, 
tachycardia, periorbital 
edema, chills, fever, 
dizziness, dyspnea, 
bronchospasm, lip 
edema, arthralgia, 
myalgia, urticaria, mild 
nausea/vomiting, 
abdominal pain, 
flatulence, somnolence, 
lethargy, headache, 
seizures (L), 
hyperuricemia  
Prompt: 
Within 2-3 weeks, 
prior to 
Hyperammonemia (L), 
coagulation abnormalities 
with prolonged PTT, PT 
Hyperglycemia, 
abnormal liver function 
tests, pancreatitis (L), 
Hemorrhage (L), DIC, 
thrombosis, anorexia, 
weight loss, CNS 

 
 
 
 
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the next course 
and bleeding times 
(secondary to decreased 
synthesis of fibrinogen, 
AT-III & other clotting 
factors) (L)  
increased serum 
lipase/amylase  
ischemic attacks, edema, 
azotemia and decreased 
renal function, mild 
leukopenia, 
granulocytopenia, 
thrombocytopenia, 
pancytopenia, hemolytic 
anemia, infections (sepsis 
with/without septic 
shock, subacute bacterial 
endocarditis [SBE], 
URI), CNS changes 
including irritability, 
depression, confusion, 
EEG changes, 
hallucinations, coma and 
stupor, paresthesias, 
hypertriglyceridemia, 
hyperlipidemia, 
Parkinson-like  
syndrome with tremor 
and increase in 
muscular tone, 
hyperbilirubinemia, 
chest pain  
Delayed: 
Any time later during 
therapy 
 
 
Renal failure, urinary 
frequency, hemorrhagic 
cystitis, elevated 
creatinine and BUN, fatty 
liver deposits, 
hepatomegaly, liver 
failure  
Unknown 
Frequency and 
Timing: 
 
Animal reproduction studies have not been conducted with pegaspargase. It is not 
known whether pegaspargase can cause fetal harm when administered to a pregnant 
woman or can affect reproduction capacity. However, fetal toxicities and teratogenic 
effects of asparaginase have been noted in animals. It is unknown whether the drug 
is excreted in breast milk.  
L)Toxicity may also occur later. 
 
 
Pemetrexed 
 
Risks and side effects related to pemetrexed include: 
Likely 
Less Likely 
Rare but Serious 
• 
Shortness of breath 
• 
A feeling of extreme 
tiredness not relieved 
by sleep  
• 
Fewer red blood cells 
in the blood  
o A low number of 
red blood cells can 
make you feel 
tired and weak 
• 
Fever 
• 
Nausea and/or vomiting 
• 
Chest pain, pain in the 
abdomen (belly) or pain in 
other parts of the body 
• 
Fewer platelets in the blood  
o A low number of 
platelets causes you to 
bruise and bleed more 
• 
Elevation in the blood of 
certain enzymes or bilirubin 
found in the liver which 
could indicate liver irritation 
or damage 
• 
Allergic reactions 
• 
Inflammation of the pancreas 
(an organ in the abdomen 
which produces insulin and 
certain digestive chemicals) 
which may affect the function 
of the pancreas and which 
may cause pain in the 
abdomen (belly) which can be 
severe and may increase the 
blood sugar. 
• 
Damage to the lungs that can 

 
 
 
 
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• 
Loss of appetite 
• 
Fewer white blood cells 
in the blood which can 
make it easier to get 
infections 
• 
Infection 
• 
Cough 
 
• 
Headache 
• 
Dizziness 
• 
Inflammation and/or sores 
in the mouth or throat 
and/or the esophagus (the 
tube that carries food from 
the mouth to the stomach) 
that may make swallowing 
difficult and are painful  
• 
Inflammation of the lining 
of the stomach 
• 
A feeling of weakness  
• 
Aches and pains in the 
muscles and joints 
• 
Rashes with itching and 
which may cause loss of 
skin 
• 
Fluid build-up under the 
skin 
• 
Hair loss 
• 
Constipation or diarrhea 
• 
Difficulty sleeping or 
falling asleep 
• 
Weight loss  
• 
Things taste differently  
• 
Chills 
• 
Hiccoughs 
• 
Excessive sweating 
• 
Inflammation and clotting 
of blood vessels which can 
lead to pain and swelling in 
the area of the clot; this 
may occur where the IV is 
placed. 
• 
Irritation to the skin if the 
medication leaks from the 
vein 
• 
Irritation to the skin at the 
site of the injection 
• 
Blurred vision, runny or 
red eyes 
• 
Reddening of the face or 
skin with feelings of 
warmth (flushing) 
• 
Low or high blood pressure 
• 
Excessive loss of water 
from the body 
(dehydration) 
• 
Low or High levels of 
certain salts in the body 
lead to fluid in the lungs and 
affect your ability to breath 
and the levels of oxygen in 
the blood.  
• 
Fever with a low white blood 
cell count which could 
indicate infection and may 
require hospitalization and 
treatment with antibiotics 
• 
Severe kidney damage (which 
may be permanent) 
• 
Severe liver damage (which 
may be permanent) 
• 
Clotting of blood vessels 
which can lead to pain and 
swelling in the area of the 
clot. Such clots may break 
loose and cause damage or be 
life-threatening depending on 
where they go. 
• Blockage of the intestines or 
bleeding in the intestines 
• Inflammation of the part of the 
intestines known as the colon 
which can lead to infection, 
blood in the stools and 
abdominal (belly) pain 
• Heart attack 
• Swelling and tightening of the 
throat (voice box) which can 
cause difficulty with breathing 
 
 
 

 
 
 
 
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like sodium, magnesium 
and potassium  
• 
Increase in heart rate 
• 
Acid or upset stomach 
(heartburn) 
• 
Too much gas produced in 
the intestines 
• 
Depression, anxiety or a 
feeling of confusion 
• 
Feeling the urgency to urinate 
or pain on urination 
• 
Increased levels of a chemical 
(creatinine) in the blood which 
could mean kidney irritation 
or damage 
• 
High levels of sugar in the 
blood that may require 
treatment 
• 
A problem in nerve function 
that may cause pain, 
numbness, tingling, and 
muscle weakness in various 
parts of the body  
• 
Inflammation or infection of 
the skin which will require 
treatment with antibiotics 
• 
Lung infection 
• 
Bladder or kidney infection 
• 
Redness or burning at the sites 
which have received radiation 
in the past 
 
 
 
Pentamidine 
 
Common ≥ 5% 
Rare < 1% 
Rash 
Loss of appetite 
Nausea 
Increased liver function test 
Nephrotoxicity 
Bronchospasm 
Cough 
Dyspnea (Inhalation form only) 
Hypotension 
Injection site pain 
Hypoglycemia 
Leukopenia (<1% with Inhalation form) 
Thrombocytopenia 
Cardiac dysrhythmia 
Skin necrosis 
Skin ulcer 
Tissue necrosis 
Acute pancreatitis 
Anemia (1.2%) 

 
 
 
 
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• 
This drug may cause nausea. Inhaled form may also cause bronchospasm, cough, and 
dyspnea. 
• 
Tell patient to report unusual bleeding/bruising or signs/symptoms of new or worsening 
infection (fever, chills, night sweats, fatigue, anorexia), nephrotoxicity, pancreatitis, or 
cardiac dysrhythmia. 
• 
This drug may cause severe hypoglycemia. Patient should be counseled on appropriate 
action to take during a hypoglycemic event. 
• 
Advise patients using inhaled form on proper nebulizer technique. 
• 
Patient should not mix other drugs with pentamidine in the nebulizer. Tell patient to 
avoid using nebulizer to give any other drugs. 
• 
Instruct patient to lie supine while receiving intravenous form. Patient should rise slowly 
after administration to avoid dizziness and other potentially severe hypotensive effects.  
• 
Patients using intravenous form should monitor IV insertion site closely during 
pentamidine infusion. Advise patient to immediately report signs/symptoms of 
extravasation, as drug is caustic. 
 
PENTOSTATIN 
Brand Name(s): Nipent 
Adverse Effects 
Serious:  
• 
Dermatologic: Rash (26% to 43%) 
• 
Endocrine metabolic: Hyponatremia (less than 3%) 
• 
Hematologic: Microangiopathic hemolytic anemia, Neutropenia, Thrombotic 
thrombocytopenic purpura 
• 
Immunologic: Immune hypersensitivity reaction (2% to 11%) 
• 
Neurologic: Neurotoxicity (1% to 11%) 
• 
Renal: Renal failure (less than 3%) 
 
Common: 
• 
Dermatologic: Disorder of skin (4% to 17%), Pruritus (10% to 21%) 
• 
Gastrointestinal: Abdominal pain (4% to 16%), Diarrhea (15% to 17%), Loss of appetite 
(13% to 16%), Nausea and vomiting (53%), Stomatitis (5% to 12%) 
• 
Hematologic: Anemia (8% to 35%), Hemorrhage (3% to 10%), Leukopenia (22% to 
60%), Thrombocytopenia (6% to 32%) 
• 
Hepatic: Increased liver function test (2% to 19%) 
• 
Immunologic: Infectious disease (7% to 36%) 
• 
Musculoskeletal: Myalgia (11% to 19%) 
• 
Neurologic: Asthenia (10% to 12%), Headache (13% to 17%) 
• 
Renal: Disorder of the genitourinary system (15%) 
• 
Respiratory: Cough (17% to 20%), Disorder of lung (12%), Dyspnea (8% to 11%), 
Rhinitis (10% to 11%), Upper respiratory infection (13% to 16%) 
• 
Other: Fatigue (29% to 42%), Fever (42% to 46%), Pain (8% to 20%), Shivering (11% to 
19%) 
 
Patient Information 
• 
Advise patient to avoid vaccines during therapy due to drug-induced immunosuppression. 
• 
This drug may cause shivering, nausea, vomiting, myalgia, headache, cough, fatigue, or 
fever. 

 
 
 
 
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• 
Patient should report signs/symptoms of hepatotoxicity, neurotoxicity, nephrotoxicity, or 
pulmonary toxicity. Patients receiving high dosages are at higher risk for these effects. 
• 
Advise patient to report angina, or signs/symptoms of cardiac dysrhythmia, heart failure 
or myelosuppression 
 
Contraindications 
• 
hypersensitivity to pentostatin or any component of the product 
 
Precautions 
• 
concomitant use with fludarabine phosphate is not recommended due to an increased 
risk of fatal pulmonary toxicity  
• 
higher than recommended doses; may increase the risk of severe renal, liver, pulmonary, 
and CNS toxicity  
• 
acute pulmonary edema and hypotension, some cases fatal, have been reported in bone 
marrow transplant patients who received pentostatin in combination with carmustine, 
etoposide, and high-dose cyclophosphamide (unapproved use)  
• 
infection, active; use caution in patients with preexisting infection; withhold pentostatin if 
active infection develops during therapy  
• 
nervous system toxicity may occur; withhold or discontinue therapy if nervous system 
toxicity occurs  
• 
neutropenia, severe or worsening of, has occurred; monitoring recommended; 
temporarily withhold therapy for severe neutropenia  
• 
rash, severe, has been reported; withhold therapy if severe rash occurs  
• 
renal impairment  
• 
renal toxicity (eg, elevated serum creatinine) has been reported; monitoring 
recommended; withhold therapy for elevated serum creatine  
 
 
PHENTOLAMINE MESYLATE 
Brand Name(s): OraVerse 
Adverse Effects 
• 
SeriousCardiovascular: Cardiac dysrhythmia, Chest pain, Hypotension, Myocardial 
infarction 
• 
Neurologic: CVA - cerebrovascular accident due to cerebral artery occlusion 
 
Common: 
• 
Dermatologic: Injection site pain (4% to 6%) 
• 
Gastrointestinal: Diarrhea (less than 3%) 
• 
Respiratory: Nasal congestion (10%) 
• 
Other: Posttreatment pain (up to 10%) 
 
Patient Information 
• 
This drug may cause nasal congestion, flushing, orthostatic hypotension, and 
arrhythmias. 
• 
Submucosal injection may cause pain at injection site. 
• 
Advise patient to report tachyarrhythmia or other signs/symptoms of cardiac dysfunction 
with parenteral forms. 
 
Contraindications 

 
 
 
 
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• 
angina  
• 
coronary artery disease, other evidence suggestive of  
• 
coronary insufficiency  
• 
hypersensitivity to phentolamine or related compounds  
• 
myocardial infarction, history or recent  
• 
specific contraindications have not been determined when used for soft-tissue anesthesia 
reversal in dental procedures (ORAVERSE(TM))  
 
Precautions 
• 
cardiovascular disease, history; increased risk of tachycardia and cardiac arrhythmias 
(ORAVERSE(TM))  
• 
cerebrovascular spasm and occlusion have been reported, usually in association with 
marked hypotensive episodes following parenteral administration  
• 
myocardial infarction has been reported, usually in association with marked hypotensive 
episodes following parenteral administration  
 
Piperazine (Estropipate) 
 
Common  
Serious 
Swelling of the limbs 
Chloasma 
Hisutism 
Bloating 
Nausea 
Stomach cramps 
Vomiting 
Headache 
Migraine 
Depression 
Mood changes 
Breast tenderness, pain, and/or swelling 
Disorder of menstruation 
Withdrawal bleeding 
Heart disease 
Hypertension 
Myocardial infarction 
Body fluid retention 
Breast cancer 
Hypercalcemia 
Gallbladder disorder 
Pancreatitis 
Deep venous thrombosis 
Venous thromboembolism 
Anaphylaxis 
Cerebrovascular accident 
Dementia 
Impaired cognition 
Thrombosis of retinal vein 
Malignat neoplasm of endometrium of corpus uteri 
Ocarian cancer 
Pulmonary embolism 
Breast cancer  
 
 
 
PIROXICAM 
Brand Name(s): Feldene 
Adverse Effects 
Serious:  
• 
None indicated 
 
Common: 
• 
Dermatologic: Injection site reaction (34%) 

 
 
 
 
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• 
Gastrointestinal: Diarrhea (37%), Nausea (34%), Vomiting (10%) 
• 
Musculoskeletal: Arthralgia (13%) 
• 
Neurologic: Dizziness (11%), Headache (22%) 
• 
Other: Fatigue (27%) 
Patient Information 
• 
Drug may cause splenic rupture. Advise patient to report left upper abdominal, scapular, 
or shoulder pain.  
• 
Drug may cause injection site reactions, headache, arthralgia, dizziness, vomiting, 
diarrhea, nausea, and fatigue.  
• 
Instruct patient to report signs and symptoms of systemic reaction (urticaria, periorbital 
swelling, dyspnea, hypoxia).  
• 
Instruct patient to report signs and symptoms of vasovagal reaction (orthostatic 
hypotension, syncope).  
 
Contraindications 
• 
specific contraindications have not been determined  
 
Precautions 
• 
leukemia; may mobilize leukemic cells and contaminate the apheresis product; use not 
recommended  
• 
peripheral blood neutrophil counts above 50,000/mcL; monitoring recommended  
• 
renal impairment, moderate and severe (CrCl 50 mL/min or less); dose reduction 
recommended  
• 
thrombocytopenia has been reported  
• 
women of childbearing potential; risk of fetal harm; avoid pregnancy using effective 
contraceptive measures  
• 
report suspected adverse reactions to the Genzyme Corporation at 1-877-4MOZOBIL or 
to the US Food and Drug Administration (FDA) at 1-800-FDA-1088 or 
www.fda.gov/medwatch  
 
 
Pravastatin Sodium   
 
Common ≥ 2% 
Rare <1% 
Diarrhea (2%) 
Flatulence (1.2%) 
Heartburn (2%) 
Nausea (1.6%) 
Vomiting (1.6%) 
Rhabdomyolysis (11.8%) 
Pancreatitis 
Hepatotoxicity 
Rupture of tendon 
 
 
This drug should be discontinued 4 to 7 days before major surgery, as patient is at higher risk 
for occurrence of rhabdomyolysis. 
 
This drug may cause nausea, vomiting, diarrhea, abdominal pain, asthenia, headache, and flu-
like symptoms. 
 
Tell patient to report signs/symptoms of rhabdomyolysis (myalgias, dark urine, arthralgias, 
fatigue) or myopathy (unexplained muscle aches, tenderness, or weakness). 

 
 
 
 
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 
Patient should take this drug at least 1 h before or 4 h after cholestyramine, colestipol or other 
bile-acid-binding resins. 
 
Patient should not drink large amounts of alcohol taking this drug. 
 
Prazosin Hydrochloride   
 
Common ≥ 1% 
Rare <1% 
Orthostatic hypotension (1-4%) 
Palpitation (5.3%) 
Syncope (1-4%) 
Nausea (4.9%) 
Asthenia (6.5%) 
Dizziness (10.3%) 
Headache (7.8%) 
Lethargy (6.9%) 
Somnolence (7.6%) 
Pancreatitis 
 
 
 
Tell patient to avoid activities requiring mental alertness or coordination until drug effects are 
realized, as drug may cause dizziness and somnolence. 
 
Instruct patient to rise slowly from a sitting/lying position, as this drug may cause orthostatic 
hypotension. 
 
Patient may experience syncope or loss of consciousness, especially within 24 h of first dose. 
 
This drug may cause angina, palpitations, tachyarrhythmia, nausea, and asthenia. 
 
Advise patient against sudden discontinuation of drug, as this may cause rebound 
hypertension. 
 
Patient should not drink alcohol while taking this drug. 
 
Prednisolone 
 
Common  
Serious 
Body fluid retention 
Hypertension 
Acne 
Ecchymosis 
Skin superinfection 
Decreased body growth 
Hyperglycemia 
Abnormal lipids 
Gastrointestinal superinfection 
Muscle weakness 
Osteroporosis 
Headache 
Cararact 
Glaucoma 
Raised intraocular pressure 
Euphoria 
Psychotic disorder 
Congestive heart failure 
Kaposi’s sarcoma 
Diabetes mellitus with hyperosmolar coma 
Diabetic ketoacidosis 
Latrogenic Cushing’s disease 
Secondary hypocortisolism 
Gastrointestinal perforation 
Pancreatitis 
Drug-induced myopathy 
Pseudotumor cerebri 
Seizure 
Pulmonary tuberculosis 

 
 
 
 
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General superinfection 
 
 
Prochlorperazine 
 
Common  
Rare <1% 
Hypotension 
Orthostatic hypotension 
Diminished sweating 
Light sensitivity 
Constipation 
Xerostomia 
Akathisia 
Dizziness 
Drug-induced tardive dystonia 
Dystonia 
Extrapyramidal disease 
Parkinsonian 
Somnolence 
Tardive dyskinesia 
Blurred vision 
Epithelial keratopathy 
Eye/vision findings 
Retinitis pigmentosa 
Nasal congestion 
Prolonged QT interval 
Torsades de pointes 
Obstipation 
Paralytic ileus 
Agranulocytosis 
Disorder of hematopoietic structure 
Leucopenia 
Thrombocytopenia 
Cholestatic jaundice syndrome 
Drug-induced lupus erythematosus, systemic 
Ineffective thermoregulation 
Heatstroke or hypothermia 
Neuroleptic malignant syndrome  
Seizure 
Priapism 
Death 
 
 
Patient should avoid activities requiring mental alertness or coordination until drug effects are 
realized, as drug may cause dizziness and somnolence. 
 
Advise patient to rise slowly from a sitting/lying position, as drug may cause orthostatic 
hypotension. 
 
This drug may cause false readings on some types of pregnancy tests. 
 
Drug may impair heat regulation. Advise patient to use caution with activities leading to an 
increased core temperature, such as strenuous exercise, exposure to extreme heat, or 
dehydration. 
 
This drug may cause anticholinergic effects, eye dryness, extrapyramidal signs, and 
progressive loss of peripheral vision. 
 
Tell patient to report signs/symptoms of tardive dyskinesia (jerky muscle movements, tongue 
thrusting, facial grimacing/ticks, random movements of extremities) or neuroleptic malignant 
syndrome (sweating, fever, stupor, unstable blood pressure, muscular rigidity, autonomic 
dysfunction). 
 
Patients using intravenous form should maintain adequate hydration to prevent volume 
depletion and hypotensive effects. Parents or caretaker of pediatric patients should report 
recent illness or dehydration before next dose is given. 

 
 
 
 
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 
Advise patient to avoid drinking alcohol or taking other central nervous system depressants 
during prochlorperazine therapy. 
 
Patient taking oral form should not take calcium- and magnesium-based antacids 
concomitantly with this drug. 
 
For patients taking multiple oral doses per day, instruct patient to take a missed dose if within 
1 h of regular dosage time, otherwise skip the missed dose and continue with regular schedule. 
 
 
 
Propylthiouracil 
 
Common 
Serious 
Rash 
Leukopenia 
Fever 
Skin rash 
Headache 
Sore throat 
Hepatic Necrosis (<1%) 
Liver failure 
Nephritis (<1%) 
 
Tell patient that symptomatic improvement may not be seen for a few weeks. 
 
Patient should immediately report, fever, skin rash, sore throat, or headache. 
 
Advise patient to report signs/symptoms of hepatic dysfunction, such as anorexia, pruritus, 
right upper quadrant pain, fatigue, weakness, abdominal pain that is vague, loss of appetite, 
itching, bruising, and yellowing of the eyes. 
 
Advise patient of importance of taking this drug regularly and at evenly spaced intervals as 
prescribed. 
 
If a dose is missed and it is almost time for the next dose, instruct patient to use two doses 
together and then return to the regular dosing schedule. 
 
Patient should contact healthcare professional if more than one dose is missed. 
 
Pyridostigmine Bromide 
  
Common 
Serious 
Diaphoresis 
Diarrhea 
Excessive salivation 
Increased peristalsis 
Nausea  
Vomiting 
Stomach cramps 
Muscle cramps  
Muscle fasciculation 
Asthenia 
Miosis 
Excessive bronchial secretion 
Bradyarrhythmia 
Cholinergic crisis 
  
 
Patient should avoid activities requiring visual clarity until drug effects are realized. 
 
This drug may cause diaphoresis, diarrhea, excessive salivation, nausea, vomiting, stomach 
cramps, muscle cramps/fasciculation, asthenia, or excessive bronchial secretions. 

 
 
 
 
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 
Patient should report increasing muscle weakness, as this could be a sign of underdosage or 
cholinergic crisis (overdosage). 
 
Advise patient to also report signs/symptoms of bradyarrhythmia. 
 
Tell patient to take drug with food or milk to minimize gastric irritation. 
 
Patient should not drink alcohol while taking this drug. 
 
Rabeprazole Sodium 
 
Common 
Serious 
Headache 
Swelling of the limbs 
Abdominal pain 
Diarrhea 
Nausea 
Dizziness 
Sleeplessness 
Stevens-Johnson syndrome 
Bone fracture (Osteoporosis-related) 
Hip fracture 
Rhabdomyolysis 
 
This drug may cause edema, abdominal pain, diarrhea, nausea, dizziness, headache, and 
insomnia. 
 
Advise patients being treated for duodenal ulcer to take drug after the morning meal. 
 
Raloxifene Hydrochloride   
 
Common 
Serious 
Hot sweats 
Leg cramps 
Deep venous thrombosis 
Venous thromboemoblism (1%) 
Verebrovascular accident 
Thrombosis of tetinal vein (<1%) 
Pulmonary embolism 
 
Advise patient to avoid sitting for prolonged periods of time, as drug increases risk of venous 
thromboembolic disorders, especially during first 4 months of therapy. 
 
This drug may cause leg cramps and hot flashes (especially during the first 6 months of 
therapy). 
 
Instruct patient to report signs/symptoms of cerebrovascular accident, pulmonary embolism, 
and deep vein thrombosis. 
 
Patient should not use cholestyramine, colestipol, or an estrogen pill, patch, or injection while 
taking this drug. 
 
 
 
 
 
 
 
 

 
 
 
 
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Ramipril 
 
Common 
Serious 
Hypotension 
Hyperkalemia 
Nausea 
Vomiting 
Dizziness 
Cough 
fatigue 
Intestinal angioedema 
Liver failure (starting with cholestatic jaundice) 
(<1%) 
Angioedema (face, lips, throat) 
• 
Patient should avoid activities requiring mental alertness or coordination until drug 
effects are realized, as drug may cause dizziness. 
• 
Advise patient to rise slowly from a sitting or lying position. 
• 
This drug may cause nausea, vomiting, persistent cough, and fatigue. 
• 
Tell patient to report signs/symptoms of angioedema (deep swelling around eyes and lips 
and sometimes hands and feet), intestinal angioedema (abdominal pain), unusual 
bleeding, or infection. 
• 
Instruct patient to maintain adequate hydration to prevent volume depletion and 
symptomatic hypotension. 
• 
Patient should avoid using potassium-containing supplements or salts while taking this 
drug. 
 
 
 
 
 
Reserpine 
 
Common 
Serious 
Dizziness 
Lethargy 
Depression 
Nasal congestion 
Chest pain 
 
Cardia dysrhythmia 
Gastrointestinal hemorrhage 
Thrombocytopenia (<1%) 
Vivid dreams 
Dream anxiety disorder 
Impotence 
• 
Patient should avoid activities requiring mental alertness or coordination until drug 
effects are realized. 
• 
This drug may cause dizziness, lethargy, nasal congestion, vivid dreams, dream anxiety 
disorder, or impotence. 
• 
Advise patient to report depression, chest pain, or signs/symptoms of gastrointestinal 
hemorrhage or cardiac dysrhythmia. 
• 
Tell patient to avoid abrupt discontinuation of drug. 
• 
Patient should not drink alcohol while taking this drug. 
• 
If a dose of reserpine is missed, advise patient to skip the missed dose and return to 
regular dosing schedule. 

 
 
 
 
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Rifampin (Rifamycin) 
 
Common 
Serious 
Abnormal color 
Sweat 
Heartburn 
Loss of appetite 
Nausea 
Saliva discoloration 
Increased liver function test 
Tear discoloration 
Discolored urine 
Flu-like illness 
Thrombocytopenia (high-dose therapy_ 
Hepatotoxcity 
• 
This drug may decrease effectiveness of oral contraceptives with concurrent use. 
Recommend additional form of birth control. 
• 
Warn patient that drug may permanently discolor soft contact lenses. 
• 
Tell patient that drug causes red-orange discoloration of urine, feces, saliva, sweat, and 
tears. 
• 
This drug may cause flu-like symptoms, heartburn, or anorexia. 
• 
Advise patient to report signs/symptoms of hepatotoxicity or thrombocytopenia. 
• 
Patient should take drug in combination with other antibiotics exactly as prescribed, as 
resistance to this drug may occur rapidly. 
• 
Tell patient to take drug 1 h before or 2 h after a meal with a full glass of water. 
• 
Patient should not drink alcohol while taking this drug. 
 
 
Rituximab 
 
Common 
Serious 
Pruritus 
Nausea 
Vomiting 
Asthenia 
Dizziness 
Headache 
Fever (all grades, 53%; grades 3 & 4, 1%) 
Shivering (all grades, 33%; grades 3 & 4, 3% 
Angina 
Cardia dysrhythmia 
Drug-induced pemphigus 
Lichenoid dermatitis 
Stevens-Johnson syndrome 
Toxic epidermal necrolysis 
Bowel obstruction 
Gastrointestinal perforation 
Anemia (all grades, 8%; grades 3 & 4, 3%) 
Aplastic anemia (transient) 
Cytopenia (grade 3 & 4, 48%) 
Hemolytic anemia 
Leukopenia (all grades 14%; grade 3 & 4, 4%) 
Lymphocytopenia (grade 3 & 4, 40%) 
Neurtropenia (all grades, 14%; grade 3 & 4, 6%) 
Thrombocytopenia (all grades, 12%; grade 3 & 
4, 2 %) 
Relapsing type B viral hepatitis 
Complication of infusion (1st infusion, 77%; 
subsequent infusions, 14-30%) 

 
 
 
 
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Allergic reaction 
Progressive multifocal leukoencephalopathy 
Nephrooxicity 
Obliterative bronchiolitis 
Pneumonitis 
Infection (all grades 31%; grades 3 & $, 4%) 
Tumor lysis syndrome 
 
Intravenous (Solution)  
• 
Fatal infusion reactions may occur within 24 hours of rituximab infusion; approximately 
80% of fatal reactions occurred with first infusion. Monitor patients and discontinue 
rituximab infusion for severe reactions. Acute renal failure requiring dialysis with 
instances of fatal outcome can occur in the setting of Tumor Lysis Syndrome following 
treatment in patients with non-Hodgkin's lymphoma. Severe and potentially fatal 
mucocutaneous reactions can occur. JC virus infection resulting in Progressive Multifocal 
Leukoencephalopathy (PML) and death can also occur. 
• 
Advise patient to avoid vaccines during therapy due to drug-induced immunosuppression. 
• 
Recommend women of childbearing potential use reliable contraception to avoid 
pregnancy during therapy and at least 12 months post-treatment. 
• 
This drug may cause nausea, vomiting, asthenia, dizziness, headache, or pruritus. 
• 
Tell patient to immediately report signs/symptoms of allergic reaction or severe 
mucocutaneous reaction such as dermatitis, Stevens-Johnson syndrome, or toxic 
epidermal necrolysis (flu-like symptoms, spreading red rash, or skin/mucous membrane 
blistering). 
• 
Patients with a history of hepatitis B should report signs/symptoms of an active infection, 
as drug may cause a relapse of hepatitis B. 
• 
Patient should also report signs/symptoms of myelosuppression, renal failure, 
hypotension, angina/cardiac dysrhythmia, or bronchiolitis/pneumonitis. 
Romidepsin 
 
Adverse Effects 
Serious:  
• 
Cardiovascular: Supraventricular arrhythmia (6%), Ventricular arrhythmia (4%), 
Hypotension (7-23%) 
• 
Hematologic: Anemia, Grades 3/4 (3% to 28%), Leukopenia, Grades 3/4 (Up to 45%), 
Neutropenia, Grades 3/4 (4% to 47%), Thrombocytopenia, Grades 3/4 (up to 36%) 
• 
Immunologic: Sepsis (5%) 
• 
Other: Tumor lysis syndrome (1% to 2%) 
Common: 
• 
Cardiovascular: EKG ST segment changes (2% to 63%) 
• 
Dermatologic: Pruritis (7-31%) 
• 
Endocrine metabolic: Weight decreased (10% to 15%); Hyperglycemia (2-51%); 
Hypermagnesemia (up to 27%); Hyperuricemia (up to 33%), Hypoalbuminemia (3-48%), 

 
 
 
 
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Hypocalcemia (4-52%), Hypokalemia (6-20%), Hypomagnesemia (22-28%), 
Hyponatremia (up to 20%), Hypophosphatemia (up to 27%),  
• 
Gastrointestinal: Loss of appetite (23% to 54%), Nausea (56% to 86%), Vomiting (34% 
to 52%), Constipation (12-40%), Diarrhea (20-36%), Altered taste sense (15-40%),  
• 
Hematologic: Anemia, All grades (19% to 72%), Leukopenia, All grades (4% to 55%), 
Neutropenia, All grades (11% to 66%), Thrombocytopenia, All grades (17% to 72%) 
• 
Hepatic: ALT/SGPT raised (3-22%), AST/SGOT raised (3-28%),  
• 
Immunologic: Infectious disease (19% to 54%), Lymphocytopenia (4% to 57%) 
• 
Neurologic: Asthenia, Headache (15% to 34%) 
• 
Respiratory: Cough (18% to 21%), Dyspnea (13-21%),Pneumonia (5%) 
• 
Other: Fatigue, Shivering (11% to 17%), Fever (20-47%) 
 
 
Rosiglitazone Maleate 
 
Common 
Serious 
Edema (4.8 to 14.7%) 
Weight gain 
Angina 
Congestive heart failure 
Myocardial infarction 
Myocardial ischemia 
Cholestatic hepatitis 
Hepatotoxicity (<1%) 
Diabetic macular edema (<1%) 
Pleural effusion 
Pulmonary edema 
• 
Premenopausal, anovulatory patients should use reliable contraception, as drug may 
stimulate ovulation. 
• 
This drug may cause edema and weight gain. 
• 
Advise patient to report signs/symptoms of congestive heart failure or pulmonary edema. 
• 
Tell patient that symptomatic improvement may not be seen for a few weeks and full 
effect of drug may not be realized until after 2 to 3 months of therapy. 
• 
Advise diabetic patients to monitor for signs/symptoms of hyper- or hypoglycemia and to 
report difficulties with glucose control, especially patients on concomitant hypoglycemic 
agents. 
Rosuvastatin Calcium 
 
Common ≥ 2% 
Rare < 2% 
Abdominal pain 
Constipation 
Nausea 
Arthralgia 
Myalgia 
Asthenia 
Headache 
Urinary tract infection 
Pharyngitis 
Flu-like illness  
Abnormal liver enzymes 
Muscle disorders 
Rhabdomyolysis 
Backache 

 
 
 
 
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Rupture of tendon 
tendinitis 
• 
This drug may cause headache and pharyngitis. 
• 
Patient should report signs/symptoms of myopathy or rhabdomyolysis (myalgias, dark 
urine, arthralgias, fatigue). 
• 
Patient should not use any aluminum- or magnesium-containing antacids for at least 2 h 
after taking this drug. 
• 
Advise patient to avoid using gemfibrozil while taking this drug. 
Saha 
 
You may have side effects while on the study.  Everyone taking part in the study will be watched 
carefully for any side effects.  However, doctors don’t know all the side effects that may happen.  
Side effects may be mild or very serious. Your health care team may give you medicines to help 
lessen side effects. Many side effects go away soon after you stop taking SAHA.  In some cases, 
side effects can be serious, long lasting, or may never go away.  The combination of SAHA and 
13-cis RA (for those children who will take both) may result in an unexpected toxicity.   
 
You should talk to your study doctor about any side effects that you have while taking part in the 
study.    
 
A child getting SAHA had blood clotting in his blood vessels, and this may be related to the 
SAHA.  
 
There have been reports of changes in blood clotting ability in patients who received both 
coumadin  
and SAHA. If you are receiving coumadin, you will be monitored carefully for signs related to 
increased risk of bleeding (such as easy bruising, bleeding from nose, gums etc.) In addition, the 
ability of your blood to clot will be watched more closely (at least monthly). 
 
 
Risks and side effects that adults who have been given SAHA had included those which are: 
 
Likely 
 
• 
Low Blood Counts: decreased red blood cells (anemia), lower numbers of white 
blood cells (infection fighting cells) which may increase your risk of infection, 
decrease in the type of blood cells that act to help stop bleeding when you are 
cut. 
• 
feeling tired  
• 
weight loss 
• 
decreased appetite 
• 
diarrhea (watery bowel movements) 
• 
nausea 
• 
vomiting 

 
 
 
 
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• 
weak kidney function 
• 
high levels of sugar in the blood 
• 
bleeding of the upper digestive tract 
Less Likely:   
 
Low Blood Counts: decreased number of a type of white blood cells, fever with dangerously low 
white blood cell count, infection that occurs when the white blood cell count is low. 
 
Heart-related: abnormal electrical conduction within the heart 
 
General: fever, chills, shivering, hair loss, infection, dehydration, dry mouth, swelling of the arms 
and legs, head pain 
 
Stomach/Intestine-related: constipation, heartburn, abnormal sense of taste, pain in the stomach    
 
Laboratory test-related: low levels of a blood protein called albumin, abnormal bone enzyme 
level,  
abnormal liver enzyme level, abnormal level of bilirubin in the blood (Bilirubin is a bile pigment 
found in the liver), low levels of potassium, sodium, phosphate, and calcium in the blood, 
increased blood magnesium level 
 
Nervous system-related: muscle spasms, muscle weakness, dizziness, condition of the nervous 
system that causes numbness, tingling, burning 
 
Breathing-related: cough, shortness of breath 
 
Vein-related: formation or presence of a blood clot inside a blood vessel, a blood test to check 
blood clotting ability 
 
Rare but Serious: 
 
• 
Death of skin cells  
 
The following side effects have been experienced by adults treated on SAHA studies, but it is not 
certain yet if they are related to taking the drug SAHA    
 
Heart-related: change in the regular beat of the heart, abnormally high or low blood pressure, 
changes in the heart rhythm which may affect blood flow, heart attack. 
 
General: sleeplessness, infection, sweating, pain throughout different parts of the body. 
 
Laboratory-test related: abnormalities in the balance of salts, proteins, sugars, and acids in the 
blood 
 
Muscle/Joint related: changes in the way you walk  
 
Nervous-system related: confusion 
 
Skin-related: hair loss, bruising, itching and rash, nail changes, tiny broken blood vessels under 
the skin. 
 

 
 
 
 
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Stomach/Intestine related: difficulty swallowing, gas, inflammation, bleeding, acid from the 
stomach flowing back up which may cause damage to the throat tissues. 
 
Breathing related:, sinus congestion, coughing up of blood from the lungs indicating possible 
lung damage.  
 
Kidney-related: retaining urine in the body, inability to control bladder, blood in urine. 
 
Vein-related: changes to the way the blood clots, blood clot within a blood vessel. 
 
Death 
 
Patients receiving SAHA also experienced the following side effects and these may be related to 
the SAHA: 
• 
a decrease in blood flowing to the brain which led to a stroke  
• 
painful mouth sores  
• 
decrease in memory function,  
• 
bleeding of the respiratory tract 
• 
kidney failure 
• 
liver failure 
• 
Loss of muscle coordination; awkward, uncoordinated walking; unsteadiness when 
walking 
 
 
Simvastatin 
 
Common 
Serious 
Constipation 
Stomach and bowel irritation 
Headache 
Upper respiratory infection 
Liver toxicity (<1%) 
Compartment Syndrome of lower leg 
Muscle disorder 
Rhabdomyolysis (<1%) 
Tendon rupture 
• 
This drug may cause constipation, gastrointestinal irritation, headache, and upper 
respiratory infection. 
• 
Patient should not drink alcohol while taking this drug. 
• 
Patient should not eat grapefruit or drink grapefruit juice while using this drug. 
Sirolimus (rapamycin) 
 
 
Common 
Happens to 21-100 
children out of every 
100 
Occasional 
Happens to 5-20 
children out of every 
100 
Rare 
Happens to <5 
children out of every 
100 
Immediate: 
Within 1-2 days of 
receiving drug 
 
Headache (L), 
hypertension (L), 
nausea, 
immunosuppression 
(L), 
diarrhea, constipation, 
Chest pain, insomnia, 
dyspepsia, vomiting, 
dyspnea 
Hypotension, asthma, 
increased cough, flu 
like syndrome, 
tachycardia, anorexia, 
sensitivity reactions 

 
 
 
 
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fever 
Prompt: 
Within 2-3 weeks, 
prior to next course 
Tremor (L), renal 
dysfunction, elevated 
creatinine/BUN 
anemia, asthenia, pain 
(abdominal, back, 
pain), 
hyperlipidemia, 
hypercholesteremia, 
hypertrigylceridema, 
hyperglycemia, 
peripheral edema, 
weight 
gain, arthralgia 
Elevated LFT’s, UTI, 
URI’s, mild 
thrombocytopenia, 
leukopenia, 
hyper/hypokalemia 
(L), 
hypophosphatemia, 
rash, 
hives, pruritis, 
hyperuricemia, 
delayed 
wound healing, 
hypomagnesaemia (L) 
Gastritis, esophagitis, 
flatulence, CNS 
abnormalities: 
(Confusion (L), 
somnolence 
(L), depression (L), 
anxiety, anxiousness, 
paresthesias, 
emotional lability, 
hypo/ 
hypertonia, dizziness, 
neuropathy, 
hypesthesia, 
nervousness), 
infections 
(bacterial, fungal, 
viral sepsis, cellulitis, 
herpes simplex & 
zoster, EBV, 
mycobacterial, 
sinusitis, pharyngitis, 
abscess, pneumonia, 
bronchitis, 
peritonitis), pleural 
effusions, pleural 
edema, hypoxia 
thrombosis, 
thrombophlebitis, 
myalgia, delayed 
wound 
healing, 
Delayed: 
Anytime later during 
therapy, excluding the 
above conditions 
Acne 
 
Skin ulcer, hirsutism 
(hypertrichosis) (L), 
gingival hyperplasia, 
abnormal vision, ear 
pain, cataracts, otitis, 
tinnitus, hemorrhage, 
ileus, chronic renal 
dysfunction, renal 
tubular necrosis, post 
transplant diabetes 
mellitus (L), CHF, 
ascites, 
thrombocytopenic 
purpura 
(hemolyticuremic 
syndrome), arthrosis, 
bone necrosis, 
osteoporosis 
Late: 
 
 
Lymphoproliferative 

 
 
 
 
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Anytime after 
completion of therapy 
disorders, skin 
malignancies 
(L) Toxicity may also occur later. 
 
Unknown Frequency and Timing: Sirolimus was embryo/feto toxic in rats at dosages of 0.1 
mg/kg and above (approximately 0.2 to 0.5 the clinical doses adjusted for body surface area). 
Embryo/feto toxicity was manifested as mortality and reduced fetal weights (with associated 
delays in skeletal ossification). Sirolimus is excreted in trace amounts in milk of lactating rats. It 
is not known whether sirolimus is excreted in human milk. 
 
Sodium Phenylbutyrate 
 
Common ≥4% 
Rare < 4% 
Lower limb swelling 
Skin rash 
Hypoalbuminemia 
Metabolic acidosis 
Alkalosis 
Hyperchloremia 
Anorexia 
Epigastric discomfort 
Abnormal menstration 
Arrythmias 
Syncope 
Hyperuricemia 
Hypokalemia 
Hypothosphatemia 
Hypernatremia 
Weight gain 
Taste aversion 
Abdominal pain 
Nausea 
Vomiting 
Gastritis 
Peptic ulcer 
Retal bleeding 
Constipation 
Pancreatitis 
Aplastic anemia 
Anemia 
Leukopenia 
Leukocytosis 
Thrombocytopenia 
Thrombocytosis 
Headache 
Depression 
Fatigue 
Somnolence 
Lightheadedness 
Disorientation 
Memory impairment 
Renal tubular acidosis 
Offensive body odor 
 
 
 
 
 
 
 

 
 
 
 
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Sorafenib 
 
Risks and side effects related to Sorafenib include those which are: 
 
Likely: 
• 
Hair loss 
• 
Inflammation of the skin on the palms of the hands or soles of the feet 
• 
Rash / flaking or shedding of outer layer of skin 
• 
Fatigue or tiredness 
• 
Loss of appetite 
• 
Diarrhea 
• 
Nausea 
• 
Low levels of a blood protein called albumin 
• 
Low blood phosphate level 
• 
Stomach ache 
 
 
 
Less Likely: 
 
Low blood counts: decrease in a red blood cell protein that carries oxygen in the body, decreased 
total number of white blood cells, decreased number of a type of white blood cell, decreased 
number of blood cells that help clot blood. 
 
Stomach / Intestine Related: bleeding in the digestive tract, constipation, painful inflammation 
and ulceration of the lining of the mouth and digestive tract, vomiting. 
 
Laboratory test-related: increased liver enzymes, abnormal liver or bone enzyme level, abnormal 
digestive enzyme level, high blood levels of a liver pigment indicative of abnormal liver function, 
low blood calcium level, high blood sugar, low blood sugar, abnormal level of fat-digesting 
enzyme, high blood potassium level, low blood potassium level, low blood sodium level. 
 
Breathing-related: shortness of breath, cough, fluid accumulation around the lungs (pleural 
effusion), voice changes (for example hoarseness, loss or change in voice), bleeding of the 
respiratory tract or lungs 
 
Skin-related: dry skin, itching. 
 
General: allergic reaction, dizziness, fever (with or without a dangerously low white blood cell 
count), weight loss, infection (with or without a low white blood cell count), pain throughout the 
body (such as back pain, chest pain, leg pain, headache, joint pain, muscle pain), difficulty 
sleeping or falling asleep. 
 
High blood pressure 
 
Bleeding in the reproductive organs or urinary system (such as the bladder or kidney) 
 
Swelling of the arms and legs 
 
Nerve damage causing numbness, tingling, or burning 
 

 
 
 
 
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Hoarseness, laryngitis, loss or change in voice 
 
Kidney failure 
 
Formation or presence of a blood clot inside a blood vessel 
 
Rare but Serious: 
 
Heart-related: decreased blood supply to the heart, heart attack, decrease in the ability of the heart 
to pump blood. 
 
Nervous system-related: bleeding into the brain or spinal cord, Syndrome caused by high blood 
pressure characterized by headache, confusion, seizures, and vision loss associated with imaging 
findings. 
 
Stomach / Intestine-related: A hole somewhere in the intestinal tract from the esophagus to the 
anus.  
 
Reproductive Risks:  You should not become pregnant or father a baby while on this study 
because the drugs in this study can affect an unborn baby.  Women should not breastfeed a baby 
while on this study. It is important you understand that you need to use birth control while on this 
study.  Check with your study doctor about what kind of birth control methods to use and how 
long to use them.  Some methods might not be approved for use in this study. Abstinence is an 
acceptable method of birth control. 
 
 
 
 
 
 
 
 
Sulfasalazine 
 
Common ≥ 3% 
Serious  
Rash (3-13%) 
Pruritus (3-4%) 
Abdominal pain (8%) 
Indigestion (13-33%) 
Loss of appetite (33%) 
Nausea (19-33%) 
Vomiting (8-33%) 
Stomatitis (4%) 
Headache (9-33%) 
Dizziness (4%) 
Oligozoospermia (reversible) (33%) 
Macrocytosis (9%) 
Fever (3-5%) 
Discolored urine 
urticaria (3%) 
abnormal liver function test (4%) 
Leukopenia (3.7%) 
Macrocytic anemia (<1%) 
Neutropenia (2%) 
Stevens-Johnson syndrome (<1%) 
Agranulocytosis (1%) 
Aplastic anemia (<1%)  
Leukopenia (<3%) 
Hemolytic anemia (<3%)  
Pure red cell aplasia (<1%) 
Thrombocytopenia (1%) 
Fulminant hepatic failure (<1%) 
Liver toxicity (<1%) 
Hypersensitivity reaction (<1%) 
Systemic lupus erythematosus (<1%) 
Central nervous system disorder (<1%) 
Myoneural disorder (<1%) 

 
 
 
 
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Hypogammaglobulinemia (10%) 
Kidney disease (<1%) 
Male infertility (<1%) 
Diffuse interstitial pulmonary fibrosis (<1%) 
• 
Inform patient that drug may cause urine/skin to turn yellow-orange color. 
• 
This drug may cause anorexia, nausea, vomiting, and headache. 
• 
Advise patient to report signs/symptoms of nephrotoxicity/hepatoxicity. 
• 
Patient should maintain adequate hydration during therapy to prevent renal stone 
formation. 
• 
Tell patients being treated for arthritis that symptomatic improvement may not be seen 
for 4 to 12 weeks. 
• 
Patient should take drug after meals. 
Sulindac 
 
Risks and side effects related to Sulindac include those which are: 
  
 
Likely 
 
Less Likely 
Rare but serious (see next 
page) 
• 
You may be 
unaware of an infection 
when the white count is 
low (neutropenia) because 
you may not develop a 
fever while taking 
Sulindac 
• 
A decrease in the 
ability of the platelets to 
clot the blood which may 
lead to bruising and to 
bleeding more easily 
 
• Acid or upset Stomach (heartburn)  
• Stomach or abdominal (belly) pain 
• Nausea and/or vomiting 
• Diarrhea or constipation 
• Headache 
• Drowsiness   
• Fluid retention which could lead to weight 
gain and puffiness  
• Ringing in the ears or a decrease in the 
ability to hear 
• Too much gas produced in the intestines 
• Cramping and discomfort in the intestines   
• Dry mouth and/or a metallic or bitter taste in 
the mouth 
• Itching and/or a rash 
• Sweating 
• Loss of appetite 
• Anxiety or depression 
• Sleepiness or inability to sleep (insomnia) 
• A feeling of weakness and/or tiredness 
• Numbness and tingling in the fingers and 
toes 
• Fainting 
• Blurred vision 
• Inflammation and/or sores in the mouth that 
may make swallowing difficult and are 
painful (painful mouth sores) 
• Inflammation of the stomach 
• Increased tendency to sun burn 
 

 
 
 
 
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Rare but serious side effects of Sulindac 
• Severe allergic reactions which can be life threatening or fatal with may include shortness of breath, low 
blood pressure, rapid heart rate, chills and fever,  aches and pains in the muscles or joints, and abnormal 
laboratory values in blood tests 
• Severe allergic reaction which can be life threatening with rapid build-up of fluid under the skin, in the 
lining of the intestine and possibly in the throat or swelling of the tongue which could make it difficult 
to breath. 
• Irritation of the small airways of your lungs that can make you cough and wheeze 
• Inflammation of the part of the intestines known as the colon which can lead to infection, blood in the 
stools and abdominal (belly) pain 
• Severe rashes which can affect the skin and mucous membranes and be life-threatening 
• Bleeding due to irritation of the gastrointestinal tract and/or from erosion of the lining of the stomach 
(an ulcer) which if untreated could rupture and may be fatal    
• Inflammation or damage to the liver which can be severe and life-threatening and which may lead to an 
enlarged liver, a yellow appearing skin, and fluid collection in the abdomen which makes it look larger. 
• Inflammation of the pancreas (an organ in the abdomen which produces insulin and certain digestive 
chemicals) which may affect the function of the pancreas and which may cause pain in the abdomen 
(belly)which can be severe and may increase the blood sugar 
• Severe damage to the kidney which may be irreversible and lead to kidney failure 
• Drugs of this type called non-steroidal anti-inflammatory drugs (NSAIDS) have been associated with 
severe cardiovascular events such as heart attack, high blood pressure or stroke. This is more likely to 
occur in patients who are older, who have had coronary artery surgery or who have diseases that make 
them more susceptible to events of this type. 
• Seizures   
• Changes in mood which may include severe depression, feelings of suicide, and feelings of 
aggressiveness  
• Temporary inflammation of the brain which could lead to a stiff neck and severe headaches. 
• Damage to the heart muscle which may make you tired, weak, feel short of breath, and retain fluid 
• Fewer white blood cells, red blood cells and platelets in the blood  
-a low number of white blood cells can make it easier 
 to get infections 
-a low number of red blood cells can make you feel 
 tired and weak 
-a low number of platelets causes you to bruise and 
    bleed more easily 
 
Sunitinib Malate 
 
Common 
Serious 
Discoloration of skin, yellow (19-30%) 
Dry skin (18%) 
Rash (14-27%) 
Hypothyroidism (3-36%) 
Abdominal pain (22%) 
Constipation (16-20%) 
Diarrhea (40-58%) 
Increased serum lipase level (25-52%) 
Indigestion (28%) 
Inflammatory disease of mucous membrane (29-
Porlonged QT interval (<0.1%) 
Severe hypothyroidism 
Gastrointestinal perforation (<1%) 
Pancreatitis (1%) 
Tumor hemorrhage (3%) 
Throbotic microangiopathy 
Liver failure (<1%) 
Posterior leukoencephalopathy syndrome, 
reversible (<1%) 
Pulmonary embolism (1%) 

 
 
 
 
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43%) 
Loss of appetite (33-38%) 
Nausea (49%) 
Mouth/tooth pain (6-10%) 
Taste aversion (21-44%) 
Vomiting (28%) 
Anemia (26-71%) 
Bleeding (18-30%)  
Leukopenia (78%) 
Lymphocytopenia (38-59%) 
Neutropenic disorder (53-72%) 
Abnormal liver function test 
Asthenia (22%) 
Increased uric acid level (41%) 
Hypertension (15-30%) 
Left ventricular cardiac dysfunction (11-21%) 
Thrombocytopenia (38-65%) 
Pulmonary hemorrhage 
Infection 
     
 
 
 
 
• 
This drug may cause yellow discoloration of skin, diarrhea, mucositis, anorexia, 
stomatitis, dyspepsia, nausea, vomiting, altered taste sense, hypertension, or asthenia. 
• 
Tell patient to report signs/symptoms of left ventricular dysfunction or congestive heart 
failure. 
• 
Patient should also report signs/symptoms of hemorrhagic events including pulmonary 
hemorrhage. 
• 
Patient should avoid eating grapefruit or drinking grapefruit juice while taking this drug. 
Sunitinib 
 
You may have side effects while on the study.  Everyone taking part in the study will be watched 
carefully for any side effects.  However, doctors don’t know all the side effects that may happen.  
Side effects may be mild or very serious. Your health care team may give you medicines to help 
lessen side effects. Many side effects go away soon after you stop taking the Sunitinib. In some 
cases, side effects can be serious, long lasting, or may never go away.  
 
You should talk to your study doctor about any side effects that you have while taking part in the 
study.  
 
Possible Risks of Heart Damage: As of December 2007, two of 12 patients treated on this study 
developed a probable side effect involving their heart function, with both patients experiencing a 
decrease in how well their hearts were able to pump blood. These effects on the heart seemed to 
improve once sunitinib was stopped.  In larger studies performed in adult patients with cancer, 
between 1 in 10 and 1 in 100 patients developed heart problems. In some cases the heart problems 
improved when treatment with sunitinib was stopped, but in other cases the problems did not 
improve when sunitinib was stopped. For children, we do not yet know how common this side 
effect actually is, and also do not know if it goes away completely once a patient stops taking 
sunitinib. However, you are only being offered to participate in this study because you have not 
previously been treated with medicines or radiation that could weaken the heart. All patients will 
have their heart function closely watched, and we will stop sunitinib if we find that it may be 
affecting your heart.   

 
 
 
 
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Other risks and side effects related to Sunitinib include those which are: 
 
Likely: 
• 
Fatigue 
• 
Loss of appetite 
• 
Diarrhea 
• 
Irritation or sores in the lining of the gastrointestinal tract 
• 
Nausea 
• 
Changes in taste 
• 
Vomiting 
• 
Stomach (belly) pain 
 
Less Likely:  
• 
Decrease in blood protein that carries oxygen 
• 
Decrease in the total number of white blood cells 
• 
Decrease number of a type of white blood cell 
• 
Decrease number of blood cells that help blood to clot 
• 
High blood pressure 
• 
Fever 
• 
Difficulty in sleeping or falling to sleep 
• 
Chills 
• 
Weight loss 
• 
Change in hair color 
• 
Dry skin 
• 
Hair loss 
• 
Lightening of the skin 
• 
Rash/flaking or shedding of outer layer of skin 
• 
Inflammation or blistering of the skin on the palms of the hands or soles of the feet 
• 
Low thyroid function 
• 
Constipation 
• 
Dehydration 
• 
Feeling of fullness 
• 
Dry mouth 
• 
Excess passing of gas 
• 
Irritation of the stomach lining 
• 
Heartburn 
• 
Nose bleed 
• 
Swelling of the arms and/or legs 
• 
Increased liver enzymes 
• 
Low levels of a blood protein called albumin 
• 
Abnormal liver or bone enzyme level 
• 
Abnormal digestive enzyme level 
• 
Increased liver pigment in blood indicative of abnormal liver function 
• 
Increased blood level of a substance normally eliminated by the kidneys into the urine 
• 
Abnormal level of fat-digesting enzyme 
• 
Decreased blood phosphate level 
• 
Increased blood levels of uric acid (a waste material from food digestion) 
 

 
 
 
 
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Less Likely (cont): 
• 
Swelling of the nerve in the back of the eye responsible for vision 
• 
Back pain 
• 
Chest pain 
• 
Leg pain 
• 
Headache 
• 
Joint pain 
• 
Muscle pain 
• 
Mouth pain 
• 
Cough 
 
Rare but serious: 
 
• 
Abnormal electrical conduction within the heart 
• 
Decrease in the ability of the heart to pump blood 
• 
Abnormal clotting of blood in small blood vessels 
• 
Swelling of a part of the eye 
• 
Decrease in vision 
 
Sunitinib may interact with other medications that you may be taking, including prescription 
medication, over-the-counter (non-prescription) medications, and herbal remedies or 
supplements.  These interactions may increase your risk of having a bad reaction to sunitinib.  Be 
sure to discuss all medications you are taking with your study doctor. 
 
Reproductive risks:  You should not become pregnant or father a baby while on this study 
because the drugs in this study can affect an unborn baby.  Women should not breastfeed a baby 
while on this study.  It is important you understand that you need to use birth control while on 
this study.  The long-term effects of sunitinib on fertility are unknown.  Check with your study 
doctor about what kind of birth control methods to use and how long to use them.  Some methods 
might not be approved for use in this study.  Pregnancy tests will be obtained in women interested 
in participating in this study. 
 
 
 
Tacrolimus 
Toxicity: 
 
Common 
Happens to 21-100 
children out of every 
100 
Occasional 
Happens to 5-20 
children out of 
every 100 
 
Rare 
Happens to < 5 children out of every 
100 
 
Immediate: 
Within 1-2 days of 
receiving drug 
  
 
Headache (L), 
hypertension (L), 
nausea,vomiting, 
anorexia, 
immunosuppression 
(L), diarrhea, 
constipation, fever 
Chest pain  
 
Anaphylaxis with the injection, 
allergic reaction, hypotension, 
asthma, dyspnea, increased cough, flu 
like syndrome, pleural effusion, 
seizure (L), tachycardia, angina 
Prompt: 
Within 2-3 weeks, 
Tremor (L), ), renal 
dysfunction (acute 
Alopecia, 
dizziness, 
Dyspepsia, dysphagia, gastritis, 
esophagitis, flatulence, CNS 

 
 
 
 
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prior to the next 
course 
 
with decrease in 
GFR, impaired 
urinary concentrating 
ability, and sodium 
retention), elevated 
creatinine/BUN, 
anemia, insomnia, 
asthenia, pain 
(abdominal, back, 
pain), hyperglycemia, 
hypomagnesemia (L), 
hyper/hypokalemia 
(L),  
hypophosphatemia, 
paresthesia 
 
elevated LFTs, 
UTI, 
peripheral edema, 
rash, pruritis, 
hyperlipidemia, 
hypercholesteremia 
 
abnormalities (confusion (L), 
somnolence (L), depression (L), 
anxiety, anxiousness, abnormal 
dreams, emotional labiality, 
hallucinations, psychosis, hypertonia, 
incoordination, neuropathy, 
nervousness encephalopathy), 
coagulation disorder, leukopenia (L), 
thrombocytopenia, polycythemia, 
anemia, leukocytosis, infections 
(bacterial, fungal, viral –sepsis, 
cellulites, fungal dermatitis, herpes 
simplex, sinusitis, pharyngitis, 
abscess, pneumonia, bronchitis, 
peritonitis), hyperbilirubinemia (L), 
thrombosis, phlebitis, arthralgia, 
myalgia, electrolyte abnormalities 
Delayed: 
Any time later 
during 
therapy, excluding 
the above conditions 
 
 
 
Acne, exfoliative dermatitis, skin 
discoloration, photosensitivity 
reaction, skin ulcer, delayed wound 
healing, hirsutism (hypertrichosis) 
(L), 
gingival hyperplasia, abnormal vision, 
amblyopia, ear pain, otitis, tinnitus, 
GI 
hemorrhage, GI perforation, 
cholelithiasis, cholestatic jaundice, 
chronic renal dysfunction, renal 
failure, post-transplant diabetes 
mellitus (L), myocardial hypertrophy, 
elevated liver function tests, liver 
damage, ascites 
 
Late: 
Any time after 
completion of 
treatment 
 
 
Lymphoproliferative disorders, skin 
malignancies 
 
Unknown 
Frequency 
and Timing: 
 
Fetal toxic effects of tacrolimus have been noted in animals. Tacrolimus is 
transported 
across the placenta and its use during pregnancy has been associated with neonatal 
hyperkalemia and renal dysfunction. Tacrolimus is excreted in human milk, nursing 
should be avoided. 
(L) Toxicity may also occur later 
 
Tamoxifen 
 
Risks and side effects related to Tamoxifen [reported side effects seen mainly in women treated for 
breast cancer at standard doses] include those which are: 
Likely 
Less Likely 
Rare but serious 
• 
Hot flashes 
• 
Reddening of the face 
• 
Nausea and/or vomiting   
• 
Bone pain 
• 
Severe rashes which can result 
in loss of skin and damage to 

 
 
 
 
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with feelings of warmth 
• 
Absence of menstrual 
flow or changes in 
menstrual flow 
(periods)  
• 
Weight gain or loss  
• 
A decrease in the sexual 
drive   
 
• 
Fluid retention 
• 
Vaginal discharge, dryness or itching 
• 
Fewer platelets in the blood  
o a low number of platelets causes 
you to bruise and bleed more 
easily 
• 
Cough 
• 
Lightheadedness or dizziness 
• 
Headache   
• 
Skin changes or rashes 
• 
Thinning of the hair or partial loss of 
hair 
• 
High levels of a certain salt in the 
body calcium which may require 
treatment 
• 
Elevation in the blood of certain 
enzymes or bilirubin found in the 
liver which could mean mild liver 
damage 
• 
Increased levels of a chemical 
(creatinine) in the blood which could 
mean kidney damage 
• 
Increase in the level of thyroxin (T4) 
which is hormone produced by the 
thyroid 
• 
An increase in the levels of lipids 
(fats) in your blood which if 
prolonged could lead to heart 
problems later in life 
• 
Changes on a test called an EKG that 
measures the activity of your hear 
mucous membranes and which 
may be life-threatening 
• 
Clotting of blood vessels which 
can lead to pain and swelling in 
the area of the clot. Such clots 
make break loose and cause 
damage or be life-threatening 
depending on where they go. 
• 
Fewer white blood cells and  
red blood cells in the blood  
o 
a low number of white 
blood cells can make it 
easier to get infections 
o 
a low number of red blood 
cells can make you feel 
tired and weak 
• 
Damage to your eye which 
could lead to a decrease in 
vision 
• 
Allergic reactions 
• 
A cyst (fluid filled sac) may 
form on the ovaries which are 
found in the abdomen (belly) 
and may be associated with 
pain 
• 
An increased risk of cancer of 
the lining of the uterus (womb) 
 
 
 
 
Tarceva (OSI-774) 
 
We know about the following side effects of OSI-774: 
 
Common 
(happens in 21-100 
patients out of 100) 
Occasional 
(happens in 5-20 
patients out of 100) 
Rare 
(happens in less than 5 patients out of 
100) 
The timing of these 
side effects (how 
soon they happen 
after taking OSI-
774) is not known. 
Acne-like skin rash, 
diarrhea, nausea, 
vomiting, tiredness, 
weariness, ill feeling 
Dry skin, dry mouth, 
decreased 
appetite, 
mouth 
sores, 
heartburn 
Peeling of the skin, hives and itching, 
elevation in liver function tests, 
redness/inflammation 
of 
the 
eye/damage to the cornea, dry eye, 
inward growth of eyelashes, tearing, 
kidney 
damage, 
headache, 
inflammation of the lungs, lung tissue 
changes and damage and scarring of 
lung tissues, blurry vision, allergic 
reaction, changes to taste, increase in 
bilirubin 

 
 
 
 
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Allergic reactions may occur with any medicine. 
 
Also reported on OSI-774 trials but with the relationship to OSI-774 unknown: low levels of red 
blood cells, low levels of white blood cells, increased numbers of white blood cells in the blood, low 
number of platelets in the blood which may increase the risk of bleeding, poor blood supply to an 
area of bone causing bone death, blockage of the pulmonary artery (1 case), a clot blocking a vein, 
shaking chills, fever, hair loss, sore throat, burning or painful sensation in the tongue, inflammation 
and cracking of the skin of the lips, constipation, abdominal pain or cramping, sores in the stomach, 
too much gas produced in the intestines, difficulty swallowing, decreased blood flow to the 
intestines, inflammation of the pancreas, blood in the urine, nose bleed, dark, bloody bowel 
movement, blood in sputum or spit, bleeding in the intestines, elevated liver enzyme levels, 
inflammation of the lungs, urinary tract infection, infection with or without decrease in a type of 
white blood cell called a neutrophil, low levels of potassium and sodium in the blood, dryness in the 
nose, runny nose, depression, anxiety, sleeplessness, a skin sensation, such as burning, prickling, 
itching, or tingling, with no apparent cause, dizziness, blockage of the blood vessels of the brain (1 
case), back pain, cough, difficulty breathing, too much protein in the urine, kidney failure, 
inflammation of the lining of the uterus, confusion, dehydration and increased levels of urea in 
the blood which is likely directly related to diarrhea, changes in blood clotting in patients also 
taking Coumadin, inflammation of the cornea causing watery painful eyes and blurred vision, 
inflammation of the eye, inflammation of the pancreas, the presence of air or gas in abnormal 
places in the body, and secondary skin infection from rash. 
 
If a person gets pregnant while receiving OSI-774, it could be dangerous for the baby. You 
should not become pregnant or father a baby while on this study. You should not nurse (breast 
feed) a baby while on this study. Ask about counseling and more information about preventing 
pregnancy. Women of child-bearing potential and males must agree to use an adequate form of 
birth control while on this protocol. 
 
 
 
Temsirolimus 
 
Risks and side effects related to temsirolimus include those which are: 
 
Likely 
• 
Low Blood Counts: low hemoglobin which means low red cell count (anemia), 
low number of platelets which help the blood to clot. 
• 
Fatigue which is a feeling of extreme tiredness not relieved by sleep 
• 
Rash including rash with peeling of the skin 
• 
Loss of desire to eat or appetite 
• 
Diarrhea 
• 
Inflammation or sores in the mouth, throat, or esophagus (the tube that leads 
from the mouth to the stomach) that may make swallowing difficult and are 
painful (painful mouth sores) 
• 
Nausea 
• 
Increase in a fat in the blood (cholesterol) which if continued for long periods of 
time could lead to heart or blood vessel problems 
 
Less Likely   
• 
Allergic reactions 
• 
Runny nose  

 
 
 
 
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• 
Low Blood Counts: low number of white blood cells which help fight infection. 
• 
An increase or decrease in blood pressure  
• 
A change in the amount of a protein that helps your blood to clot 
• 
Fever  (high body temperature) 
• 
Difficulty sleeping or falling asleep 
• 
Chills and shaking chills 
• 
Weight loss 
• 
Dry Skin 
• 
Nail changes 
• 
Itching of the skin 
• 
Rash and acne (pimples) 
• 
Hives 
• 
Wound complication 
• 
Low levels of testosterone, a hormone found in the body 
• 
Diabetes, a condition which causes an inability to tolerate glucose (sugar) in the 
body 
• 
Constipation 
• 
Feeling bloated, tightness or pain in the belly 
• 
Mouth sores 
• 
Taste alteration where things taste differently 
• 
Vomiting 
• 
Fever with a low white blood cell count which could indicate infection and may 
require hospitalization and treatment with antibiotics 
• 
Risk of bleeding 
• 
Risk of infection 
• 
Fluid build-up in the arms, legs, head or neck. 
• 
Acidosis that is metabolic (through your body’s system) or respiratory (in the 
lungs). 
• 
Abnormal amounts of liver enzymes 
• 
Low amounts of calcium 
• 
High levels of glucose (sugar) in the blood which may require treatment 
• 
An increase in the levels of lipids (fats) in your blood which if prolonged could 
lead to heart problems later in life 
• 
Low levels of certain salts in your body (such as potassium and phosphate) 
• 
Increase of triglycerides in the blood which could lead to heart problems later in 
life 
• 
Depression 
• 
Somnolence which is a feeling of sleepiness, an inability to stay awake or aware 
• 
Pain (such as belly, back, chest, head, joint, or muscle pain) 
• 
Cough 
• 
Shortness of breath 
• 
Nose or sinus reactions 
• 
Inflammation of the lungs that can lead to fluid in the lungs and affect your 
ability to breath and the levels of oxygen in your blood making you short of 
breath 
• 
Erectile dysfunction 
• 
Decreased libido, which means a decrease in sexual desire 
• 
Flu type symptoms with fever, tiredness, aches and pains 
 

 
 
 
 
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Rare but serious 
• 
Holes or tears in the gastrointestinal tract (including the stomach, intestine and 
colon). 
• 
Severe kidney damage (which may be permanent)  
• 
Clotting of blood vessels which can lead to pain and swelling in the area of the 
clot. Such clots may break loose and cause damage or be life-threatening 
depending on where they go. 
 
Reproductive risks:  You should not become pregnant or father a baby while on this study 
because the drugs in this study can affect an unborn baby.  Women should not breastfeed a baby 
while on this study.  These precautions should be in place for the whole duration of the study 
therapy and for at least 3 months after the last dose of temsirolimus due to the long half lives of 
these drugs.  It is important you understand that you need to use birth control while on this study.  
Check with your study doctor about what kind of birth control methods to use and how long to 
use them.  Some methods might not be approved for use in this study. 
 
 
 
Temozolomide 
 
Risks and side effects related to temozolomide include those which are: 
Likely 
Less Likely 
Rare but can be Serious 
• 
Fewer red and white blood 
cells and platelets in the 
blood  
o a low number of red 
blood cells can make 
you feel tired and weak 
o a low number of white 
blood cells can make it 
easier to get infections 
o a low number of 
platelets causes you to 
bruise and bleed more 
easily 
• 
Nausea 
• 
Vomiting 
• 
Constipation 
• 
Loss of appetite 
 
 
• 
Diarrhea 
• 
Headache 
• 
Tiredness 
• 
Difficulty swallowing 
• 
Dizziness 
• 
Anxiety or depression 
• 
Difficulty sleeping 
• 
Rash 
• 
Itching 
• 
Increased need to urinate 
• 
Urinary Tract Infections 
• 
Mouth sores 
• 
Fluid Build up in legs and 
arms 
• 
Hair loss 
• 
Elevation in the blood of 
certain enzymes found in 
the liver 
• 
Visual disturbances that 
may cause double vision 
• 
Forgetfulness or confusion 
• 
Aches and pains in muscles 
and joints 
• 
Pain in the abdomen 
 
• 
Convulsions 
• 
Severe allergic reaction 
which can be life 
threatening with 
shortness of breath, low 
blood pressure, rapid 
heart rate, chills and 
fever 
• 
Low numbers of white 
blood cells called 
lymphocytes that may 
last a long time and 
make it easier to get 
infections which may be 
life-threatening 
• 
Partial paralysis or 
weakness of one side of 
the body 
• 
Blood clots which may 
be life-threatening 
• 
A new cancer or 
leukemia resulting from 
this treatment 
(L) Toxicity may also occur later. 
 

 
 
 
 
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Thalidomide 
 
Common 
Serious 
Swelling of the limbs (4.2% to 56.9%) 
Rash (30.4%) 
Hypocalcemia (71.6%)  
Hypokalemia (22.5%) 
Hyponatremia (43.1%) 
Hypothyroidism (20%) 
Increased appetite (21.6%) 
Weight loss (22.5%) 
Constipation (54.9%) 
Nausea (28.4%) 
Leukopenia (35.3%) 
Confusion (28.4%) 
Somnolence (37.5%) 
Tremor (4.2% to 25.5%) 
Neutropenia (31.4%) 
Thrombosis (22.5%) 
Peripheral neuropathy (21.6% to 53.9%) 
Increased liver function test (24.5%) 
Increased serum bilirubin (13.7%) 
Joint pain (12.7%) 
Bone pain (30.4%) 
Muscle pain (16.7%) 
Muscle weakness (40.2%) 
Headache (12.5% to 19.6%) 
Sleeplessness  (22.5%) 
Dizziness/lightheadedness (4.2% to 19.6%) 
Anxiety (25.5%) 
Fatigue (79.4%) 
Stevens-Johnson syndrome 
Toxic epidermal necrolysis 
Teratogenesis 
Pulmonary embolism 
Seizure (rare) 
Loss of menstruation (<0.1%) 
      
Oral (Capsule)  
• 
Thalidomide can cause severe birth defects or death to an unborn baby if taken during 
pregnancy. Women of childbearing potential should have a pregnancy test before starting 
therapy, then weekly for first month, and monthly thereafter. Effective contraception 
must be used for at least 4 weeks before beginning thalidomide therapy, during 
thalidomide therapy, and for 4 weeks following discontinuation of thalidomide therapy. 
Males must always use a latex condom during any sexual contact with women of 
childbearing potential. Only prescribers and pharmacists registered with the 
S.T.E.P.S.(R) distribution program can prescribe and dispense thalidomide. The use of 
thalidomide in multiple myeloma results in an increased risk of venous thromboembolic 
events, such as deep vein thrombosis and pulmonary embolus. 
• 
This drug may decrease effectiveness of oral contraceptives with concurrent use. Instruct 
patient to use 2 forms of reliable contraception to avoid pregnancy during therapy and at 
least 4 weeks before and after therapy. 
• 
Male patients must use a latex condom during intercourse during any sexual contact with 
women of childbearing potential, even if patient has had a vasectomy. 

 
 
 
 
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• 
Tell patient to avoid activities requiring mental alertness until drug effects are realized, as 
this drug may cause dizziness and somnolence. 
• 
Patient should rise slowly from a sitting/lying down position. 
• 
This drug may cause edema, constipation, nausea, confusional state, and tremors. 
• 
Advise patient to immediately report signs/symptoms of Stevens-Johnson syndrome/toxic 
epidermal necrolysis (flu-like symptoms, spreading red rash, or skin/mucous membrane 
blistering), thromboembolism (shortness of breath, chest pain, or arm/leg swelling), or 
pregnancy. 
• 
Patient should also report signs/symptoms of infection, bleeding, or peripheral 
neuropathy (numbness, tingling, pain, or burning in hands/feet). 
• 
Advise patient to closely follow healthcare professional's instructions regarding 
frequency of taking pregnancy test. 
• 
Tell patient to take drug at bedtime at least 1 h after evening meal. 
• 
Patient should not drink alcohol while taking drug. 
 
 
Theophylline 
 
Common 
Serious 
Nausea  
Vomiting 
Headache 
Insomnia 
Tremor 
Irritability  
Restlessness 
Attial fibrillation 
Trachyarrhythmia 
Stevens-Johnson syndrome 
Intracranial hemorrhage 
Seizure 
• 
Advise patient that this drug is not indicated for acute asthma attacks or other respiratory 
flare-ups. 
• 
This drug may cause nausea, headache, insomnia, tremors, and restlessness. 
• 
Patient should immediately report signs/symptoms of theophylline toxicity (vomiting, 
arrhythmia, seizures). 
• 
Advise patient to report signs/symptoms of infection or any changes in ongoing health, as 
healthcare professional may need to make dose adjustments. 
• 
Serious toxicity is not necessarily preceded by mild/moderate side effects. Inform patient 
that regular blood work is important to ensure therapeutic drug level. 
• 
Instruct patient to take drug the same way every dose. Patient should choose to take drug 
always with food or always without food, as this influences drug level. 
• 
Counsel patient to avoid abruptly discontinuing or changing dosage without supervision 
by healthcare professional. 
• 
Patient should inform provider of significant changes in diet (such as "low carb" diet, 
increased caffeine) and smoking habits (start/stop smoking tobacco or marijuana, 
increased exposure to second-hand smoke). 
• 
Advise patient there are multiple significant drug-drug interactions for this drug. Consult 
healthcare professional prior to new drug use (including over-the-counter and herbal 
drugs). 

 
 
 
 
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Thioguanine 
 
Common 
Serious 
Loss of appetite 
Nausea 
Stomatitis 
Vomiting 
Hyperuricemia 
Gastrointestinal necrosis (with combination 
regimens) 
Perforation of intestine 
Myelosuppression 
Hepatotoxicity 
Jaundice  
Abnormal liver function test 
Infection 
• 
Patient should avoid vaccines during therapy due to drug-induced immunosuppression. 
• 
Advise patient on the proper handling and disposal of chemotherapy drugs. 
• 
This drug may cause anorexia, nausea, stomatitis, and vomiting. 
• 
Advise patient to immediately report signs/symptoms of bleeding (unexplained bruising, 
black tarry stools, hematuria, purpura) or infection. 
• 
Instruct to report signs/symptoms of gastrointestinal toxicity or hepatotoxicity (jaundice, 
right upper quadrant pain, weight gain, ascites).  
• 
Encourage patient to maintain adequate hydration to prevent hyperuricemia. 
• 
Patient should not drink alcohol while taking this drug. 
Thioguanine Toxicity: 
 
 
Common 
Happens to 21-
100 children out 
of every 100 
Occasional 
Happens to 5-20 
children out of 
every 100 
Rare 
Happens to < 5 children out of 
every 100 
Immediate: 
Within 1-2 days of 
receiving drug 
 
Anorexia, 
nausea, 
vomiting, 
diarrhea, malaise 
Urticaria, rash, hyperuricemia 
 
Prompt: 
Within 2-3 weeks, 
prior to 
next course 
Myelosuppression 
 
Toxic hepatitis (L), increased 
SGOT (AST)/SGPT (ALT), 
ataxia, mucositis 
Delayed: 
Anytime later during 
therapy 
 
 
Hepatic fibrosis(L), sinusoidal 
obstruction syndrome (SOS, 
formerly VOD) (L), 
hyperbilirubinemia 
Unknown 
Frequency and 
Timing: 
Fetal toxicities and teratogenic effects of thioguanine have been noted in 
animals. It is unknown whether the drug is excreted in breast milk. 
• 
(L) Toxicity may also occur later. 
 
 
 
 
 

 
 
 
 
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Thioridazine Hydrochloride 
 
Common 
Serious 
Hypotension 
Orthostatic hypotension 
Diminished sweating 
Light sensitivity (rare) 
constipation 
Xerostomia 
Akathisia 
Dizziness 
Drug-induced tardive dystonia 
Systonia 
Extrapyramidal disease 
Parkinsonian 
Somnolence 
Tardive dyskinesia 
Blurred vision 
Epithelial keratopathy 
Eye/vision change 
Retinitis pigmentosa 
Urinary retention 
Nasal congestion 
Porlonged QT interval (rare) 
Sudden cardiac death  
Torsades de pointes (rare) 
Obstipation (rare) 
Paralytic ileus (rare) 
Agranulocytosis (rare) 
Disorder of hematopoietic structure (rare) 
Leukopenia (rare) 
Thrombocytopenia (rare) 
Cholestatic jaundice syndrome (rare) 
Drug-induced lupus erythematosus (rare) 
Systemic (rare) 
Ineffective thermoregulation, 
heatstroke/hypothermia (rare) 
Neuroleptic malignant syndrome (rare) 
Seizure (rare) 
Priapism (rare) 
Death 
• 
Patient should avoid activities requiring mental alertness or coordination until drug 
effects are realized, as drug may cause dizziness or somnolence. 
• 
Instruct patient to rise slowly from a sitting/supine position, as drug may cause orthostatic 
hypotension. 
• 
This drug may cause hypotension, anticholinergic effects, akathisia, dystonia, epithelial 
keratopathy, retinitis pigmentosa, or nasal congestion. 
• 
Tell patient to report signs/symptoms of arrhythmia or tardive dyskinesia (jerky muscle 
movements, tongue thrusting, facial grimacing/ticks, random movements of extremities). 
• 
Advise patient there are multiple significant drug-drug interactions for this drug. Consult 
healthcare professional prior to new drug use (including over-the-counter and herbal 
drugs). 
• 
Patient should avoid drinking alcohol while taking this drug. 
 
 
 
Thiotepa 
 
Risks and side effects related to the Thiotepa are listed below: 
 
Likely 
Less Likely 
Rare but serious 
• 
Nausea  
• 
Vomiting 
• 
Loss of appetite 
• 
A feeling of extreme tiredness or 
weakness 
• 
Fewer white blood cells, red blood cells 
• 
Pain at the injection site 
• 
Dizziness 
• 
Headache 
• 
Blurred vision 
• 
Hives, skin rash 
• 
Wheezing 
• 
Severe allergic 
reaction which can 
be life threatening 
with shortness of 
breath, low blood 
pressure and a 

 
 
 
 
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and platelets in the blood. 
○ A low number of red blood cells 
can make you feel tired and weak. 
○ A low number of white blood cells 
can make it easier to get infections. 
○ A low number of platelets causes 
you to bruise and bleed 
• 
Absence or decrease in the number of  
sperm which may be temporary or 
permanent which may decrease the 
ability to have children 
• 
Absence or decrease in monthly periods 
and could affect your ability to become 
pregnant 
 
With High Doses used before marrow 
transplants:  
• 
Inflammation and/or sores in the 
mouth, throat and/or esophagus (the 
passage between the throat and 
stomach) 
• 
Sudden high fever 
• 
Pain in the abdomen 
• 
Difficulty emptying the bladder 
• 
Feeling the urgency to urinate or pain 
on urination 
• 
Hair loss 
• 
Inflammation and reddening of the 
eye 
• 
Inflammation of the skin where the 
drug comes into contact with the skin 
 
With High Doses used before marrow 
transplants:  
• 
inappropriate behavior  
• 
confusion 
• 
drowsiness 
• 
Elevation in the blood of certain 
enzymes and/or bilirubin found in the 
liver 
• 
Bronze discoloration or darkening of 
the skin 
rapid heart rate 
• 
Swelling and 
tightening of the 
throat which can 
cause difficulty 
with breathing 
• 
A new cancer or 
leukemia resulting 
from this treatment 
 
 
 
 
 

 
 
 
 
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Tolbutamide 
 
Common 
Serious 
Cutaneous hypersensitivity 
Hypoglycemia 
Hyperglycemia 
Heartburn 
Nausea 
Death (cardiovascular, reported in 
University group diabetes program) 
Severe hypoglycemia (0.35%) 
 
 
 
• 
This drug may cause heartburn or nausea. 
• 
Drug may cause hypo- or hyperglycemia. Instruct patient to monitor for and report 
problems with glycemic control. 
• 
Tell patient to report stress due to infection, fever, trauma, or surgery, as dosing 
adjustments may need to be made. 
• 
Advise patient to avoid drinking alcohol while taking this drug. 
Tolcapone  
 
Common 
Serious 
Constipation 
Diarrhea 
Loss of appetite 
Nausea 
Xerostomia 
Dream disorder  
Sleep disorder 
Orthostatic hypotension 
Hyperpyrexia 
Fulminant hepatic failure (rare) 
Rhabdomyolysis 
Confusion 
Dyskinesia 
Dystonia 
Hallucinations 
 
 
 
 
• 
Patient should avoid activities requiring mental alertness or coordination until drug 
effects are realized, as drug may cause dizziness and drowsiness. 
• 
Advise patient to rise slowly from a lying/sitting position, as this drug may cause 
orthostatic hypotension. 
• 
This drug may cause diarrhea, loss of appetite, nausea, anticholinergic effects, dystonia, 
dyskinesia, and hyperpyrexia (very high fever). 
• 
Drug may also cause hallucinations and dream/sleep disorders. 
• 
Advise patient to report signs/symptoms of acute renal failure or hepatic dysfunction 
(persistent nausea, fatigue, dark urine, pruritus, right upper quadrant tenderness, jaundice, 
clay-colored stools). 
• 
May take with food to minimize gastric irritation. 
• 
Advise patient against sudden discontinuation of drug. 
 
 
 
 
 

 
 
 
 
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Tolmetin 
 
Common 
Serious 
Swelling of the limbs 
Weight gain 
Weight loss 
Abdominal pain 
Diarrhea 
Flatulence 
Indigestion 
Nausea 
Vomiting 
Asthenia 
Dizziness 
Headache 
Congestive heart failure (<1%) 
Hypertension (3-9%) 
Myocardial infarction (<2%) 
Thrombotic tendency observations 
Erythema multiforme (<1%) 
Scaling eczema 
Stevens-Johnson syndrome 
Toxic epidermal necrolysis (<1%) 
Gastrointestinal hemorrhage (<1%) 
Gastrointestinal perforation  
Digestive tract inflammation 
Agranuloscytosis (<1%) 
Anemia (<3%) 
Neutropenia (<1%) 
Thrombocyutopenia (<1%) 
Hepatitis (<1%) 
Increased liver function test (increased up 
to15%) 
Jaundice (<1%) 
Liver failure (<0.1%) 
Allergic reaction (<1%) 
Cerebrovascular accident 
Acute kidney failure (<1%) 
Hematuria (<1%) 
Proteinuria (<1%) 
Brochospasm 
• 
 Elderly and debilitated patients may be at higher risk for serious gastrointestinal adverse 
effects while taking this drug. 
• 
This drug may cause edema, weight gain or loss, abdominal pain, diarrhea, dyspepsia, 
flatulence, nausea, vomiting, asthenia, dizziness, and headache. 
• 
Advise patient to report signs/symptoms of thrombotic events, myocardial infarction, or 
stroke. 
• 
Instruct patient to report signs/symptoms of gastrointestinal bleeding or ulceration. 
 
Topiramate 
 
Common 
Serious 
Diarrhea (5-11%) 
Loss of appetite (4-24%) 
Nausea (6-14%) 
Altered sense of taste (3-15%) 
Weight loss (6-21%) 
Confusion (3-14%) 
Language disorder (6-10%) 
Dizziness (8-32%) 
Nervous feelings (7-14%) 
Erythema mutiforme 
Stevens-Johnson syndrome 
Toxic epidermal necrolysis 
Increased body temperature 
Hperammonemia (with or without 
encephalopathy) 
Hypohidrosis 
Metabolic acidosis (7% to 67%) 
Liver failure 

 
 
 
 
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Headache 
Impaired psychomotor performance (3-21%) 
Memory impairment (5-14%) 
Paresthesia (2-51%) 
Reduced concentration span (4-14%) 
Somnolence (9-29%) 
Speech and language disorder 
Abnormal vision (2% to 13%) 
Diplopia (1% to 10%) 
Nystagmus (10% to 11%) 
Fatigue (14% to 30%) 
Glaucoma 
Myopia 
Depression (3% to 13%) 
Mood disorder (2% to 11%) 
Suicidal thoughts 
Nephrolithiasis (1% to 3%) 
• 
Patient should avoid activities requiring mental alertness and coordination until drug 
effects are realized, as drug may cause dizziness, somnolence, and motor retardation.  
• 
Drug may impair heat regulation, especially in pediatric patients. Advise patient to use 
caution with activities leading to an increased core temperature, such as strenuous 
exercise, exposure to extreme heat, or dehydration.  
• 
Drug may decrease effectiveness of estrogen-containing oral contraceptives with 
concurrent use. Recommend additional form of birth control with oral contraceptives.  
• 
Drug may cause nausea, diplopia, nervousness, dysmenorrhea, breast pain, and fatigue.  
• 
Drug may cause asthenia, ataxia, confusion, speech and language problems, memory 
impairment, nystagmus, paresthesias, tremors, and inability to concentrate.  
• 
Advise patient to report signs/symptoms of acute myopia associated with angle-closure 
glaucoma (sudden decreased visual acuity, ocular pain).  
• 
Advise patient against sudden discontinuation of drug, as this may cause increased 
seizure activity.  
• 
Patient should avoid concomitant use of valproic acid. Hyperammonemia with 
encephalopathy is possible.  
TOPOTECAN: 
 
 
 
Common 
 
Occasional 
 
Rare 
Immediate:  
Nausea, vomiting, diarrhea (L), 
mouth sores (L), flu-like 
symptoms (L), headache, 
rashes (L), increased liver 
enzymes in the blood 
Stomach pain, shaking chills 
Within 2-3 
wks: 
Decrease in the number of red 
and white blood cells and 
platelets made in the bone 
marrow, hair loss 
 
 
Delayed: 
 
Loss of strength or energy 
Tiny amounts of blood in the 
urine 
Late: 
 
 
 
• 
 
• 
(L) Toxicity may also occur later. 
 
 
 
 
 

 
 
 
 
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Torsemide 
 
Common 
Serious 
Orthostatic hypotension 
Electrolyte imbalance (2-4%) 
Hyperuricemia  
Constipation (2%) 
Diarrhea (2%) 
Indigestion (2%) 
Nausea (2%) 
Muscle cramp 
Dizziness (3%) 
Fatigue 
Headache (7%) 
Insomnia (1%) 
Nervous feeling (1%) 
Excessive urination (7%) 
Cough (2%) 
Rhinitis (3%) 
Ototoxicity (rare) 
• 
Patient should avoid activities requiring mental alertness or coordination until drug 
effects are realized. 
• 
Advise patient to rise slowly from a lying/sitting position, as this drug may cause 
orthostatic hypotension. 
• 
This drug may cause headache and excessive urination. 
• 
Instruct patient to report signs/symptoms of ototoxicity (tinnitus, hearing loss). 
 
Tranylcypromine 
Common 
Serious 
Edema 
Orthostatic hypotension 
Weight gain 
Constipation 
Diarrhea 
Loss of appetite 
Nausea 
Xerostomia 
Asthenia 
Dizziness 
Headache 
Insomnia 
Somnolence 
Impotence 
Hypertensive crisis 
Agranulocytosis (rare) 
Anemia (rare) 
Leucopenia (rare) 
Thrombocytopenia (rare) 
Hepatitis (rare) 
Worsening depression (rare) 
Suicidal thoughts (rare) 
Suicide (rare) 
• 
Patient should avoid activities requiring mental alertness or coordination until drug 
effects are realized, as drug may cause dizziness or somnolence. 
• 
Instruct patient to rise slowly from a sitting/supine position, as drug may cause orthostatic 
hypotension. 
• 
This drug may cause edema, weight gain, anticholinergic effects, diarrhea, anorexia, 
nausea, asthenia, headache, insomnia, agitation, anxiety, manic behavior, or impotence. 

 
 
 
 
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• 
Advise patient that full symptomatic improvement may not be seen for up to 3 weeks. 
• 
Instruct patient to report worsening depression, suicidal ideation, or unusual changes in 
behavior, especially at initiation of therapy or with dose changes. Children and 
adolescents are at higher risk for these effects during the first few months of therapy. 
• 
Advise patient against sudden discontinuation of drug. 
• 
Advise patient there are multiple significant drug-drug interactions for this drug. Consult 
healthcare professional prior to new drug use (including over-the-counter and herbal 
drugs). 
• 
Patient should not drink alcohol while taking this drug. 
• 
Tell patient to limit amount of caffeine during therapy. 
• 
Patient should avoid eating foods high in tyramine while taking this drug, as this may 
cause extremely high blood pressure. High tyramine foods include dried or very ripe 
fruits, liver, sausage, and other meats, and aged or fermented foods/drinks such as wine, 
cheese or pickles. 
Trastuzumab 
 
Risks and side effects related to trastuzumab include those which are: 
Likely 
Less Likely 
Rare but serious 
• 
Diarrhea 
The following reactions are 
more common with the first 
dose of tratuzumab but could 
occur with any infusion of the 
drug 
• 
Nausea and vomiting 
• 
Headache 
• 
Rash during the infusion 
• 
Fever and chills including 
shaking chills.   
• 
Feeling short of breath 
• 
Pain in the abdomen, the   
back or at the tumor site 
• 
A feeling of tiredness or 
weakness 
• A decrease or an increase in 
blood pressure 
 
• Damage to the heart muscle 
which may make you tired, 
weak, feel short of breath, 
and retain fluid* 
• A feeling of tiredness 
• Muscle and joint aches and 
pains 
• Bone, chest and nerve pain 
• Numbness and tingling in 
the fingers and toes 
• Fluid retention and  build-
up in the tissues usually of 
the lower legs leading to an 
increase in weight  
• Inflammation of the 
sinuses, the throat and nose 
which could lead to pain or 
pressure, runny nose or 
change in your voice 
• Infections including 
bladder or kidney 
infections and skin 
infections 
• Wheezing and/or shortness 
of breath 
• Rash, hives or itchiness  
• Acne 
• Rash with skin sores 
• Fast or irregular heart beat 
during the infusion 
• Mouth Sores with 
inflammation and pain 
• 
Allergic reactions during the 
infusion that can be severe and 
life-threatening and may lead to 
difficulty in breathing, a drop in 
blood pressure, irregular heart 
beat, a sudden stopping of the 
heart (cardiac arrest), fluid in the 
lungs or damage to the lungs and 
shock.** 
• 
Fewer white blood cells, red 
blood cells and platelets in the 
blood  
o a low number of white blood 
cells can make it easier to get 
infections 
o a low number of red blood 
cells can make you feel tired 
and weak 
o a low number of platelets 
causes you to bruise and 
bleed more easily 
• Severe allergic reaction which can 
be life threatening with rapid 
build-up of fluid under the skin, in 
the lining of the intestine and 
possibly in the throat or swelling 
of the tongue which could make it 
difficult to breath. 
• Sudden, temporary feeling of 
chest tightness, wheezing or 
coughing making it difficult to 
breath which can occur during or 
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•  Loss of desire to eat 
• Dizziness or fainting 
• Cough 
• Depression 
• Difficulty sleeping 
• Elevation in the blood of 
certain enzymes found in 
the liver 
• Fever with a low white 
blood cell count which 
could indicate infection 
and may require 
hospitalization and 
treatment with antibiotics 
 
shortly after the infusion 
• Inflammation and scarring of the 
lungs that can lead to fluid in the 
lungs and affect your ability to 
breath and the levels of oxygen in 
your blood. 
• Damage to the heart which can 
lead to inflammation of the heart 
muscle and a build-up of fluid 
around the heart which may be 
painful and affect the ability of 
the heart to work normally 
• Damage to the kidneys that causes 
protein to be lost from the blood 
by leaking from the kidneys into 
the urine and causing swelling 
usually in the legs and ankles 
from fluid build-up in body 
tissues. 
 
 
            * Trastuzumab rarely causes decreases in heart function when administered by itself. 
When Trastuzumab is given alone, these changes in heart function are usually reversible.  
When Trastuzumab is given in combination with chemotherapy drugs called 
anthracyclines (for example doxorubicin) or cyclophosphamide, there is a much greater 
risk of heart damage, though this complication is still uncommon. Such damage can 
result in a rapid heart beat, decreased pumping strength of the heart, and accumulation 
of fluid in the lungs which may rarely interfere with breathing. 
          **Some patients may have a severe of life-threatening reaction during or after treatment 
with Trastuzumab.  These reactions can involve a drop in blood pressure and shortness 
of breath, and have resulted in death in several patients.  These severe reactions may be 
more common in patients who already have breathing difficulties or lung disease.  If you 
develop any clear discomfort during or after a treatment with Trastuzumab, you should 
contact your physician immediately or go to the nearest Emergency Care facility. 
 
Trazodone 
 
Common 
Serious 
Sweating symptom 
Weight change 
Constipation 
Diarrhea 
Loss of appetite 
Nausea 
Vomiting 
Xerostomia 
Dizziness 
Headache 
Insomnia 
Lethargy 
Memory impairment 
Cardiac diysrhythmia (rare) 
Hypertension (rare) 
Hypotension (rare) 
Hemolytic anemia (rare) 
Leukocytosis (rare) 
Methemoglobinemia (rare) 
Seizure (rare) 
Worsening depression (rare) 
Suicidal thoughts (rare) 
Suicide (rare) 
Priapism (rare) 

 
 
 
 
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Somnolence 
Blurred vision 
• 
Patient should avoid driving and other activities requiring mental alertness or 
coordination until drug effects are realized, as this medicine may cause dizziness or 
somnolence. 
• 
This drug may cause sweating, weight change, anticholinergic effects, diarrhea, anorexia, 
nausea, vomiting, headache, insomnia, lethargy, and memory impairment. 
• 
Advise patient that symptomatic improvement may not be seen for 2 to 4 weeks. 
• 
Instruct patient to report worsening depression, suicidal ideation, or unusual changes in 
behavior, especially at initiation of therapy or with dose changes. Children and 
adolescents are at higher risk for these effects during the first few months of therapy. 
• 
Patient should take with food or milk. 
• 
Advise patient against sudden discontinuation of drug. 
• 
Patient should not drink alcohol while taking this drug. 
Valproic acid 
Risks and side effects related to the valproic acid include those which are: 
Likely: 
• 
nausea 
• 
vomiting 
• 
abdominal pain 
• 
diarrhea 
• 
headache  
• 
sleepiness 
• 
tremor 
• 
loss of strength and energy 
• 
dizziness 
• 
hair loss 
• 
rash 
• 
dry skin 
• 
itching of the skin 
• 
numbness and tingling of your hands and/or feet 
• 
short-term weakness of your hands and/or feet 
 
Less Likely: 
• 
loss of appetite 
• 
heartburns 
• 
flu-like syndromes 
• 
double vision 
• 
blurred vision 
• 
unsteadiness 
• 
unsteady eye movement 
• 
sleeplessness 
• 
loss of memory 

 
 
 
 
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• 
moodiness 
• 
anxiety or nervousness 
• 
ringing in the ear 
• 
pneumonia 
• 
weight gain or loss  
• 
abnormal thyroid function 
• 
low platelet count, which may cause easy bruising or bleeding 
• 
abnormal blood clotting which can lead to excessive bleeding during and after surgery 
Rare but can be serious: 
• 
sores in the mouth or on the tongue 
• 
hyperactivity 
• 
confusion 
• 
coma 
• 
severe reactions involving skin, mouth, and eyes, including blisters 
• 
redness, swelling, and/or peeling of your skin, resulting in pain and infection 
• 
eye pain and irritation 
• 
low white and/or red blood cell count  
• 
abnormal effects on unborn babies (see “Risks of Pregnancy”, below) 
• 
severe to life-threatening inflammation of the pancreas and liver 
• 
hearing loss 
• 
abnormal sodium level in the blood 
• 
fast and/or irregular heart beats, high blood pressure 
• 
peeing frequently, vaginal yeast infection  
• 
inflammation of the kidney 
• 
irregularities in your periods, including complete stoppage of your periods 
• 
gum bleeding or swelling, infection around your teeth 
• 
abnormal change in the bone marrow leading to chronic transfusions, and possibly leading 
to a pre-leukemia condition called myelodysplastic syndrome. 
• 
abnormal clotting tests and possibly increased risk of bleeding 
 
 
Vandetanib 
 
Adverse Effects 
Serious:  
• 
Cardiovascular: Heart failure (0.9%), Prolonged QT interval (all Grades, 14%; Grade 3-
4, 8%) 
• 
Dermatologic: Stevens-Johnson syndrome 
• 
Gastrointestinal: Pancreatitis (0.4%) 
• 
Hematologic: Hemorrhage, Decreased platelet count (9%), Neutropenia (10%) 
• 
Immunologic: Sepsis 
• 
Neurologic: Ischemic stroke (1.3%), Reversible posterior leukoencephalopathy 
syndrome 
• 
Respiratory: Aspiration pneumonia, Interstitial lung disease, Respiratory arrest, 
Respiratory failure 
 

 
 
 
 
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Common: 
• 
Cardiovascular: Hypertension (all Grades, 33%; Grade 3-4, 5%) 
• 
Dermatologic: Acne (all Grades, 35%; Grade 3-4, 1%), Rash (all Grades, 53%; Grade 3-
4, 5%), Dry Skin (15%), Photosensitivity (13%), Pruritis (11%) 
• 
Endocrine metabolic: Decreased calcium level (all Grades, 57%; Grade 3-4, 6%), 
Decreased glucose level (24%), Hypomagnesemia (7%), Decreased weight (10%) 
• 
Gastrointestinal: Abdominal pain (all Grades, 21%; Grade 3-4, 3%), Colitis, Diarrhea, 
Loss of appetite (all Grades, 21%; Grade 3-4, 4%), Nausea (all Grades, 33%; Grade 3-4, 
1%) 
• 
Hepatic: ALT/SGPT level raised (all Grades, 51%; Grade 3-4, 2%) 
• 
Neurologic: Headache (all Grades, 26%; Grade 3-4, 1%), Asthenia (15%) 
• 
Opthalmic: Blurred vision (9%) 
• 
Psychiatirc: Depression (10%) 
• 
Renal: Proteinuria (10%), Serum creatinine raised (16%) 
• 
Respiratory: Cough (11%),Nasopharyngitis (11%) 
• 
Other: Fatigue (all Grades, 24%; Grade 3-4, 6%) 
 
 
 
Verapamil 
 
Common 
Serious 
Edema 
Hypotension 
Constipation 
Nausea 
Dizziness 
Headache 
Angina (rare) 
Myocardial infarction (rare) 
Syncope (rare) 
• 
Patient should avoid activities requiring mental alertness or coordination until drug 
effects are realized, as this medicine may cause dizziness and light-headedness. 
• 
This drug may cause edema, constipation, nausea, and headache. 
• 
Patient should watch for signs/symptoms of hypotension with initial dosing and dose 
changes. 
• 
Advise patient against sudden discontinuation of drug, as this may precipitate 
hypertensive rebound/crisis. 
• 
Patient should not drink alcohol while taking this drug. 
 
 
 
 
 
 
 

 
 
 
 
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Vinblastine 
 
Risks and side effects related to Vinblastine include those which are: 
Likely 
Less Likely 
Rare but serious 
• 
Hair loss 
• 
Fewer white blood 
cells, red blood cells 
and platelets in the 
blood 
o a low number of 
red blood cells can 
make you feel tired 
and weak 
o a low number of 
white blood cells 
can make it easier 
to get infections 
o a low number of 
platelets causes you 
to bruise and bleed 
more easily 
• Constipation 
• Diarrhea 
• Nausea and /or vomiting 
• Loss of Appetite 
• Reversible nerve problem that may 
affect the way you walk or the 
feelings in your fingers or toes 
(Numbness and tingling) or may 
make you feel weak  
• A hoarse voice 
• Mouth sores 
• Depression 
• Jaw pain 
• Bone pain 
• Headache 
• A feeling or tiredness or not well 
• Rash and a tendency to burn more 
easily in the sun (very rarely 
reported) 
• Inflammation and discomfort in the 
vein through which the medicine was 
given 
• A sore throat 
• Pain and bloating in your abdomen 
• Drooping eyelids 
• Double vision 
• Rapid, jerky movements of the eye 
which are not under your control and 
can alter your vision 
• Difficulty with urination or increase 
desire to urinate 
• Abnormal hormone function which 
may lower the level of salt in the 
blood 
• Damage to the ear causing hearing 
loss which maybe temporary or 
permanent, balance problems 
(dizziness) and ringing in the ears 
• Absence or decrease in the number of 
sperm and/or damage to the testis 
which may be temporary or 
permanent which may decrease the 
ability to have children in the future 
• Absence of menstrual cycles 
(periods) and damage to the ovaries 
that may decrease the ability to have 
• Complete stoppage of your 
intestinal activity which can 
result in intestinal blockage 
• If the drug leaks out of the 
vein when being administered 
it will cause damage to nearby 
tissue 
• The rapid death of large 
numbers of tumor cells which 
can cause the uric acid in the 
blood to rise quickly and this 
could lead to damage to the 
kidneys.  
• Seizures 
• A sudden onset of shortness 
of breath which may be 
accompanied by wheezing 
and/or coughing and a feeling 
of tightness in the chest 
• Fluid build up in the lungs 
• A heart attack or an abnormal 
heart rhythm 
• Bleeding from the 
gastrointestinal tract including 
from a stomach ulcer, the 
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children in the future 
• Temporary inflammation of the liver 
leading to an elevation in the blood of 
certain enzymes found in the liver 
• High blood pressure 
• Blanching (whiteness) of the fingers 
or toes when they are exposed to cold 
or when you are under stress, that 
may make them feel cold or throb and 
ache 
 
Vinorelbine  
 
Likely 
Happens to 10-30  patients out of 
every 100 
Less Likely 
Happens to 3-10 patients out of 
every 100 
Rare But Serious 
Happens to less than 3 patients 
out of every 100 
• 
Injection 
site 
reactions 
including 
redness, 
pain 
and vein discoloration 
• 
Nausea 
• 
Vomiting 
• 
A drop in white blood cells 
and red blood cells in the 
blood 
o a low number of red 
blood cells can make 
you 
feel 
tired 
and 
weak 
o a low number of white 
blood cells can make it 
easier to get infections 
• 
Tiredness 
• 
Constipation 
• 
Increased 
liver 
enzyme 
levels 
• 
Diarrhea 
• 
Hair loss 
• 
Fever 
• 
A drop in platelets in the 
blood 
o a low number of platelets 
causes you to bruise and 
bleed more easily 
• 
Muscle weakness 
• 
Inflammation of 
the 
vein 
through which the drug was 
given 
• 
Decreased appetite 
• 
Reversible 
nerve problem 
that may affect the way you 
walk or the feelings in your 
fingers or toes, the likelihood 
of which increases with the 
number of doses 
• 
Pain in your abdomen 
• 
Mouth sores 
• 
Rash 
• 
Increased 
bilirubin 
which 
may 
result 
in 
a 
yellow 
appearance 
• 
Increased 
or 
decreased 
blood pressure 
• 
Muscle aches 
• 
Redness and peeling skin on 
the palms and soles 
• 
Hearing loss 
• 
Headache 
• 
Jaw pain 
• 
Bleeding of the bladder 
• 
A return of redness and 
inflammation at a site of 
previous radiation therapy 
• Severe 
allergic 
reaction 
which 
can 
be 
life 
threatening with shortness 
of 
breath, 
low 
blood 
pressure, rapid heart rate, 
chills and fever 
• Complete stoppage of your 
intestinal activity which can 
result in intestinal blockage 
and damage 
• Fluid buildup in the lungs 
• Difficult 
breathing 
or 
shortness of breath 
• Chest pain or heart attack 
• If the drug leaks out of the 
vein 
when 
being 
administered it may cause 
damage to nearby tissue 
• Liver damage 
• Inflammation 
of 
the 
pancreas 
• Clots in veins such as the 
ones in the legs or lungs 
• Severe shortness of breath 
and respiratory failure due 
to injured lungs that can be 
fatal 

 
 
 
 
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Vorinostat 
 
Risks and side effects related to the vorinostat include those which are: 
Likely 
• 
Low Blood Counts: decreased red blood cells that carry oxygen in the body 
(anemia), decrease in a type of white blood cell called neutrophils, decreased 
total numbers of white blood cells (infection fighting cells) which may increase 
your risk of infection, decrease in the type of blood cells called platelets that help 
to clot blood. 
• 
fatigue 
• 
weight loss 
• 
loss of appetite 
• 
diarrhea 
• 
nausea 
• 
vomiting 
• 
high blood level of creatinine, a substance normally eliminated by the kidneys 
into the urine 
• 
high level of sugar in the blood 
 
 
 
 
 Less Likely   
• 
Low Blood Counts: decreased number of a type of white blood cell called 
lymphocytes 
• 
changes in heart rhythm 
• 
abnormal levels of blood protein in a blood test to check blood clotting ability 
• 
fever 
• 
chills 
• 
hair loss 
• 
constipation 
• 
dehydration 
• 
dry mouth 
• 
heartburn 
• 
taste alteration 
• 
fever with dangerously low white blood cell count 
• 
infection 
• 
swelling of the limbs such as the arms or legs 
• 
low levels of a blood protein called albumin 
• 
abnormal liver or bone enzyme level 
• 
abnormal liver enzyme level 
• 
abnormal level of bilirubin in the blood.  Bilirubin is a bile pigment found in the 
liver. 
• 
decreased  blood calcium level 
• 
increased blood magnesium  level 
• 
decreased blood phosphate level 
• 
decreased blood potassium level 

 
 
 
 
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• 
decreased blood sodium level 
• 
muscle spasms 
• 
muscle weakness 
• 
dizziness 
• 
Condition of the nervous system that causes numbness, tingling, burning. 
• 
pain in the abdomen or belly 
• 
headache 
• 
cough 
• 
shortness of breath 
• 
formation or presence of a blood clot inside a blood vessel. 
 
Rare but serious 
• 
death of the skin tissue called tissue necrosis 
 
 
Zolendronic acid 
 
Likely 
Happens to 10-
30  patients out 
of every 100 
Less Likely 
Happens to 3-10 patients out of every 100 
Rare But Serious 
Happens to less than 3 patients 
out of every 100 
• Fatigue 
(tiredness) 
• Flu-like 
symptoms 
including 
fever, chills, 
and joint and 
muscle aches, 
which are 
generally seen 
after the first 
infusion 
• Low levels of 
calcium in the 
blood which 
may cause 
muscle cramps 
• Anorexia (loss 
of appetite) 
 
 
 
 
 
 
 
• Headaches 
• Insomnia 
• Anxiety 
• Stomach irritation 
• Bone, back, muscle, and joint pain 
• Tachycardia (rapid heart rate) 
• Abnormal kidney function tests 
• Diarrhea 
• Tingling in the fingers and toes 
• Nausea, vomiting, constipation, and /or 
abdominal pain 
• Low red blood cell counts which may 
cause tiredness, shortness of breath or 
fatigue 
• Allergic reactions, which include itching, 
flushing, rash, and shortness of breath 
• Low levels of potassium, magnesium, 
and/or phosphate in the blood. In almost all 
cases, you would not experience symptoms 
from these effects. If these levels fall to 
extremely low levels, possible side effects 
could include muscle twitching, muscle 
weakness, and abnormal heart rhythm. 
• A reaction at the injection site, which 
might include pain, redness, tenderness, 
swelling, and/or bruising. 
• Kidney failure 
• Severe allergic reactions 
• Permanent damage to the jawbone 
that may be painful and might 
require surgery to remove the 
damaged area.  There is more 
information about this below.* 
This might be more likely to 
happen in patients who have 
certain dental procedures. If you 
see a dentist, you should inform 
them that you are receiving 
zoledronic acid. 
• Serious eye problems. If you 
suspect you are having an eye side 
effect after receiving the study 
drug, you should call the study 
doctor.  
• Chest pain 
• Red puffy eyes (conjunctivitis) 
• Low platelets (increased risk for 
bleeding) 
• Low white blood count (increased 
risk of infection)  
• Low blood pressure 
*A condition called osteonecrosis of the jaw (ONJ) has been seen in patients taking zoledronic 
acid or other bisphosphonates. This happens in less than 1% of patients.  ONJ can show up as a 
non-healing wound in the gum tissue covering the jaw bone, or roof of the mouth, that exposes 
the bone. The wound can be painful, can worsen over time and often involves an infection in the 
area with ONJ. This means a portion of the jawbone becomes permanently damaged, may be 

 
 
 
 
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painful, and may require dental treatment or removal of the damaged area.  Little is known about 
how the wound develops. Based on available evidence, a causal relationship between ONJ and 
bisphosphonates, including zoledronic acid, has not been established.  Most of the patients who 
got ONJ had cancer and were receiving repeated monthly doses of bisphosphonates and most 
were also receiving chemotherapy and corticosteroids.  Other risk factors for ONJ include 
radiotherapy and concurrent medical conditions (for example, anemia, a defect in the blood 
clotting mechanism, infection and pre-existing oral disease).  In most cases, the patient also had 
surgery in the mouth or a tooth removed.  ONJ has been much less frequently reported in non-
cancer patients taking bisphosphonates.  For patients requiring oral surgery, there are no data 
available to suggest whether stopping bisphosphonate treatment reduces the risk of ONJ.  In 
patients who develop ONJ, surgery at the affected area may make the condition worse.  If you 
think you have this condition see your Study Doctor and dentist immediately. 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Appendix IV: Intervention Insights Whole Body Reference Set 
 
Tissue 
Tissue Sub Detail 
Brain 
Amygdala 
Esophagus 
  
Brain 
Corpus Callosum 
Large 
Intestine 
Cecum 
Small 
Intestine 
Jejunum 
Prostate 
Gland 
  
Tonsil 
  
Salivary Gland 
Submandibular Gland 
Brain 
Amygdala 
Nipple 
  
Lymph Node 
  
Testis 
  
Prostate 
Gland 
  
Corpus Uteri 
  
Brain 
Temporal Lobe L 
Brain 
Accumbens 
Skeletal 
Muscle 
Quadriceps Femoris 
Brain 
Accumbens 
Brain 
Putamen 
Brain 
Entorhinal Cortex 
Brain 
Putamen 
Adrenal 
Gland 
  
Corpus Uteri 
Myometrium 
Corpus Uteri 
Myometrium 
Liver 
  
Uterus 
Endometrium 
Uterus 
Endometrium 
Brain 
Substantia Nigra 
Heart 
  
Brain 
Hippocampus 
Kidney 
Medulla 
Corpus Uteri 
Endometrium 
Skin 
  
Bronchus 
  
Brain 
Frontal Lobe NOS 
Brain 
Hippocampus 
Corpus uteri 
Myometrium 
Skin 
  

 
 
 
 
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Spleen 
  
Small 
Intestine 
Ileum 
Brain 
Brain, Subthalamic Nucleus 
Brain 
Thalamus 
Brain 
Accumbens 
Brain 
Occipital Cortex 
Gland 
Pituitary Gland 

 
 
 
 
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Appendix V: OncInsights Method Summary Diagram 
 
 
The total number of drugs that can be selected by the OncInsights service is 327.  The diagram 
represents the total number of drugs which can be selected by each method.  Because one or more 
drugs can be selected by one or more methods the sum of drugs listed in the figure will not equal 
the unique drug count.