9.6
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                                                                                                                                                                                                                                                                                                                                                                                                                          |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 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. |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          |                                                                                                                                                                                                                                                                                                                                                                                                                                      |
| Unrelated                                                                                                                                                                                                                                                                                                                                                                                   |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          |                                                                                                                                                                                                                                                                                                                                                                                                                                      |
| Unrelated to  investigational                                                                                                                                                                                                                                                                                                                                                               |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          |                                                                                                                                                                                                                                                                                                                                                                                                                                      |
| agent/intervention                                                                                                                                                                                                                                                                                                                                                                          | 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.                                                                                                                     |                                                                                                                                                                                                                                                                                                                                                                                                                                      |
| Unlikely                                                                                                                                                                                                                                                                                                                                                                                    | 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. |                                                                                                                                                                                                                                                                                                                                                                                                                                      |
| Possible                                                                                                                                                                                                                                                                                                                                                                                    | 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.                                                                                                                                          |                                                                                                                                                                                                                                                                                                                                                                                                                                      |
| Related to                                                                                                                                                                                                                                                                                                                                                                                  |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          |                                                                                                                                                                                                                                                                                                                                                                                                                                      |
| investigational                                                                                                                                                                                                                                                                                                                                                                             |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          |                                                                                                                                                                                                                                                                                                                                                                                                                                      |
| agent/intervention                                                                                                                                                                                                                                                                                                                                                                          | Probable                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 | 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. |
| Definite                                                                                                                                                                                                                                                                                                                                                                                    |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          |                                                                                                                                                                                                                                                                                                                                                                                                                                      |
9.6
11 subject withdrawal and trial

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.
9.6
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.  
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.
9.6
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.
9.6
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.  
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.
9.6
13.2 ethical conduct of the

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.
9.6
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.
9.6
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 the case report forms when the monitor visits the investigational site. All information obtained from source documents will be kept in strict confidentiality.
9.6
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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9.6
appendix i performance status/scores

| Performance Status Criteria                                                              |                                     |                                       |                                |                                   |                                   |
|------------------------------------------------------------------------------------------|-------------------------------------|---------------------------------------|--------------------------------|-----------------------------------|-----------------------------------|
| Kamofsky and Lansky performance scores are intended to be multiples of 10                |                                     |                                       |                                |                                   |                                   |
| ECOG (Zubrod)                                                                            | Karnofsky                           | Lansky*                               |                                |                                   |                                   |
| Score                                                                                    | Description                         | Score                                 | Description                    | Score                             | Description                       |
| 100                                                                                      | Normal, no complaints, no           | 100                                   | Fully active, normal.          |                                   |                                   |
| evidence of disease                                                                      |                                     |                                       |                                |                                   |                                   |
| Fully active, able to cany on all                                                        |                                     |                                       |                                |                                   |                                   |
| 0                                                                                        | pre-disease performance             | 90                                    | 90                             | Minor restrictions in physically  |                                   |
| without restriction.                                                                     | Able to cany on normal              |                                       |                                |                                   |                                   |
| activity, minor signs or                                                                 | strenuous activity.                 |                                       |                                |                                   |                                   |
| symptoms of disease.                                                                     |                                     |                                       |                                |                                   |                                   |
| 80                                                                                       | Normal activity with effort;        | 8                                     | Active, but tires more quickly |                                   |                                   |
| Restricted in physically                                                                 | some signs or symptoms of           |                                       |                                |                                   |                                   |
| strenuous activity but                                                                   | disease.                            |                                       |                                |                                   |                                   |
| ambulatory and able to carry                                                             |                                     |                                       |                                |                                   |                                   |
| !                                                                                        | out work of a light or sedentary    | 70                                    | Cares for self, unable to cany | 70                                | Both greater restriction of and   |
| nature, e.g., light housework,                                                           |                                     |                                       |                                |                                   |                                   |
| office work.                                                                             | on normal activity or do active     | less time spent in play activity.     |                                |                                   |                                   |
| work.                                                                                    |                                     |                                       |                                |                                   |                                   |
| 60                                                                                       | Required occasional                 | 60                                    | Up and around, but mimmal      |                                   |                                   |
| assistance, but is able to care                                                          | active play, keeps busy with        |                                       |                                |                                   |                                   |
| Ambulatory and capable of all                                                            | for most of his/her needs.          | quieter activities.                   |                                |                                   |                                   |
| self-care but unable to carry out                                                        |                                     |                                       |                                |                                   |                                   |
| 2                                                                                        | any work activities. Up and         | 50                                    | Requires considerable          | 50                                | Gets dressed, but lies around     |
| about more than 50% of waking                                                            | assistance and frequent             | much of the day; no active play,      |                                |                                   |                                   |
| hours                                                                                    | medical care.                       | able to participate in all quiet play |                                |                                   |                                   |
| and activities.                                                                          |                                     |                                       |                                |                                   |                                   |
| 40                                                                                       | Disabled, requires special care     | 4                                     | Mostly in bed; participates in |                                   |                                   |
| Capable of only limited self-                                                            | and assistance.                     | quiet activities.                     |                                |                                   |                                   |
| care, confined to bed or chair                                                           |                                     |                                       |                                |                                   |                                   |
| 3                                                                                        | more than 50% of waking             | 30                                    | Severely disabled,             | 30                                | In bed; needs assistance even for |
| hours.                                                                                   | hospitalization indicated.          | quiet play.                           |                                |                                   |                                   |
| Death not imminent.                                                                      |                                     |                                       |                                |                                   |                                   |
| 20                                                                                       | Very sick, hospitalization          | 20                                    | Often sleeping; play entirely  |                                   |                                   |
| indicated. Death not                                                                     | limited to very passive activities. |                                       |                                |                                   |                                   |
| Completely disabled. Cannot                                                              | imminent.                           |                                       |                                |                                   |                                   |
| 4                                                                                        | cany on any self-care. Totally      |                                       |                                |                                   |                                   |
| confined to bed or chair.                                                                | 10                                  | Moribund, fatal processes             | 10                             | No play; does not get out of bed. |                                   |
| progressing rapidly.                                                                     |                                     |                                       |                                |                                   |                                   |
| The conversion of the Lansky to ECOG scales is intended for NCI reporting purposes only. |                                     |                                       |                                |                                   |                                   |
appendix ii biology studies collection
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
appendix ii biology studies collection
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
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
instructions for incision/excision surgery specimen
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  
| 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                   |
| Version 2.0 Final                                                      | Page 76 of 268     | Confidential        |                             |
| Issued 12 June 2013                                                    |                    |                     |                             |  
| 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 |                 |
instructions for incision/excision surgery specimen
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.  
- 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.  
- Adrenal gland failure
- Chronic noncongestive angle-closure glaucoma
- Cirrhosis
- Hyponatremia/hypokalemia - Hyperchloremic acidosis - Hypersensitivity to acetazolamide - Severe hepatic or renal disease  
- 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.
instructions for incision/excision surgery specimen
generic drug name acetazolamide brand

- **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)
- Instruct patient to report polyuria if increased urination affects sleep.  
- Patient should avoid concomitant high-dose aspirin.  
- 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 StevensJohnson 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  
| Common                      | Serious                                                                                                                              |
|-----------------------------|--------------------------------------------------------------------------------------------------------------------------------------|
| Indigestion Nausea Vomiting | Bleeding (3.9%, high-dose use) Tinnitus  dyspepsia  Bronchospasm  Angioedema  Reye's syndrome Gastrointestinal ulcer (long term use) |
instructions for incision/excision surgery specimen
acetylsalicylic acid

- 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.  
| 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 lupuslike 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.
instructions for incision/excision surgery specimen
albendazole adverse effects serious

- **Dermatologic:** Erythema multiforme, Stevens-Johnson syndrome
- **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
instructions for incision/excision surgery specimen
aldesleukin risks and side effects

| 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                                                                      |                    |                                                                                                                                                             |
| Version 2.0 Final | Page 81 of 268                                                                                                                                                                                                                                                                               | Confidential       |                                                                                                                                                             |  
Page 81  
| 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 lifethreatening                                                                                                                                                                                                                                            |                                                                                      |
| -                                                                                    | 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                                                                                                                                                                                                                               |                                                                                      |  
| 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.
instructions for incision/excision surgery specimen
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%)  
- **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.
instructions for incision/excision surgery specimen
amikacin adverse effects serious

- **Neurologic:** Neuromuscular blockade finding, tremor, paresthesia, weakness,
- **Central Nervous System:** Fever, headache, drowsiness, dizziness, ataxia, vertigo - **Otic:** Ototoxicity
- **Renal:** Nephrotoxicity
- **Respiratory:** Respiratory tract paralysis  
- **None indicated**  
| 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.
instructions for incision/excision surgery specimen
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  
- **Gastrointestinal:** Nausea, Vomiting - **Neurologic:** Asthenia, Dizziness, Headache  
| 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.
instructions for incision/excision surgery specimen
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 Page 86  
- Central Nervous System: Drowsiness (14%)
- **Gastrointestinal:** Constipation (12%), Xerostomia (14%) - **Neurologic:** Somnolence (14%) - **Ophthalmic:** Blurred vision (7%)
- **Dermatologic:** Edema, Skin Rash - **Other:** Fatigue (14%)
instructions for incision/excision surgery specimen
amoxicillin serious

- **Dermatologic:** Stevens-Johnson syndrome, Toxic epidermal necrolysis
- **Gastrointestinal:** Hemorrhagic colitis
- **Immunologic:** Anaphylaxis  
- **Gastrointestinal:** Diarrhea (frequent)
instructions for incision/excision surgery specimen
ampicillin

Brand Name(s): Amcill ; Omnipen ; Penbritin ; Pfizerpen-A ; Polycillin ; Rosampline ;
Totacillin
instructions for incision/excision surgery specimen
adverse effects serious

- **Dermatologic:** Erythema multiforme, Erythroderma, Stevens-Johnson syndrome, Toxic epidermal necrolysis
- **Gastrointestinal:** Pseudomembranous enterocolitis
- **Hematologic:** Agranulocytosis, Thrombocytopenia
- **Immunologic:** Anaphylaxis, Hypersensitivity reaction  
- **Dermatologic:** Rash, Urticaria - **Gastrointestinal:** Diarrhea  
- 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.  
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.  
| 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%) |              |
| Version 2.0 Final                                                                                                                                                                                                                                                                      | Page 88 of 268                                                                                                                                                                                                                                                                                                                                                      | Confidential |
| Issued 12 June 2013                                                                                                                                                                                                                                                                    |                                                                                                                                                                                                                                                                                                                                                                     |              |  
| 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.
instructions for incision/excision surgery specimen
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
instructions for incision/excision surgery specimen
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) |              |
| Version 2.0 Final                                                                                                                                                                                 | Page 89 of 268                                                                                                                                                                                                                                                                                                                                                   | Confidential |  
Page 89  
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.
instructions for incision/excision surgery specimen
atovaquone adverse effects serious

- **Dermatologic:** Erythema multiforme, Stevens-Johnson syndrome
- **Hematologic:** Methemoglobinemia
- **Hepatic:** Liver failure  
- **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%)
instructions for incision/excision surgery specimen
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%)
- **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%)  
- **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%)  
| 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%) |  
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.  
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).
instructions for incision/excision surgery specimen
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%)  
- **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%)
instructions for incision/excision surgery specimen
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  
| 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 |
instructions for incision/excision surgery specimen
bcnu

| Rare                                                                                                                                    |                                                                                                                                                        |                         |
|-----------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------|
| Happens to <5 children out  of every 100                                                                                                |                                                                                                                                                        |                         |
| Immediate:                                                                                                                              | Burning feeling in the vein                                                                                                                            |                         |
| Within 1-2 days                                                                                                                         | while drug is being given,                                                                                                                             |                         |
| of receiving drug nausea, vomiting Common Happens to 21-100 children  out of every 100                                                  | Occasional                                                                                                                                             |                         |
| Happens to 5-20 children  out of every 100                                                                                              | 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                                                                                        | Inflammation and/or  blockage of a vein at the  injection site (L), sudden  redness of the face                                                        |                         |
| 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 | Abnormal function of the                                                                                                                               |                         |
| liver (L)                                                                                                                               | kidneys (L)                                                                                                                                            |                         |
| Delayed:                                                                                                                                | Abnormal lung function (L)                                                                                                                             | Damage/scarring of lung |
| Any time later                                                                                                                          | tissue (L)                                                                                                                                             |                         |
| during therapy,  excluding the  above conditions Late: Any time after  completion of  treatment                                         | A new cancer or leukemia  resulting from this treatment.                                                                                               |                         |
| (L) Toxicity may also occur later.                                                                                                      |                                                                                                                                                        |                         |
instructions for incision/excision surgery specimen
betamethasone adverse effects serious

- **Endocrine metabolic:** Cushing's syndrome, Hyperglycemia, Primary adrenocortical insufficiency
- **Musculoskeletal:** Osteoporosis - **Ophthalmic:** Cataract, Glaucoma - **Respiratory:** Pulmonary tuberculosis Common:
- **Cardiovascular:** Hypertension
- **Dermatologic:** Atrophic condition of skin, Finding of skin healing Skin infections (1643%)**Endocrine metabolic:** Decreased body growth
- **Gastrointestinal:** Disord**er of gastrointestina**l tract
- **Immunologic:** At risk for infection
- **Psychiatric:** Depression, Euphoria
instructions for incision/excision surgery specimen
bevacizumab

| 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 Rare Happens to <5 patients out of  every 100 Immediate:  Within 1-2 days  of receiving  drug  Occasional Happens to 5-20 patients  out of every 100 High blood pressure,  low blood pressure,  fever, chills, shaking  chills, headache, nausea,  vomiting Difficulty breathing,  Allergic Reaction cough or voice change 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 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  Infection, joint pains,  chest pains, low blood  counts*, fatigue, weight  loss, loss of appetite,  change in bowel habits.   |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
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.
instructions for incision/excision surgery specimen
biotin brand name(s) appearex adverse

- gastrointestinal upset
- administration of anticonvulsant medications may impair Biotin absorption
instructions for incision/excision surgery specimen
bisacodyl brand name(s) alophen pills

- **Gastrointestinal:** Abdominal colic, Abdominal discomfort, Diarrhea, Proctitis, With suppository use  
- 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.  
- appendicitis
- intestinal obstruction - gastroenteritis
instructions for incision/excision surgery specimen
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
instructions for incision/excision surgery specimen
risks and side effects related

- 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
- 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
instructions for incision/excision surgery specimen
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  
- **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%)
instructions for incision/excision surgery specimen
budesonide serious

- **Cardiovascular:** Syncope (inhalation, 1% to 3%); Chest Pain (0-3%), Palpitations (05%), 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)  
- 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%)
instructions for incision/excision surgery specimen
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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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
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buspirone serious

- **Cardiovascular:** Congestive heart failure (rare), Myocardial infarction (rare) - **Neurologic:** Cerebrovascular accident (rare)  
- **Gastrointestinal:** Nausea (3%)
- **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%)
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calcitriol adverse effects serious

- **Dermatologic:** Dermatitis, Acute blistering - **Endocrine metabolic:** Poisoning by vitamin D, Hypercalcemia syndrome Common:
- **Endocrine metabolic:** Hypercalcemia
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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%)  
| 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                                                                                                                                                                                                                                                                                                               |  
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 StevensJohnson 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.  
| Common                           | Serious                                                                            |              |
|----------------------------------|------------------------------------------------------------------------------------|--------------|
| Loss of appetite Nausea Vomiting | Heart disease Othostatic hypotension (1%) Dyskinesia (frequent) Psychotic disorder |              |
| Version 2.0 Final                | Page 102 of 268                                                                    | Confidential |
| Issued 12 June 2013              |                                                                                    |              |
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carbidopa/levodopa 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
instructions for incision/excision surgery specimen
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                                                                                                                                                                                                                                                                               |                    |                                                                                                                             |
| Version 2.0 Final   | Page 103 of 268                                                                                                                                                                                                                                                                                      | Confidential       |                                                                                                                             |
| Issued 12 June 2013 |                                                                                                                                                                                                                                                                                                      |                    |                                                                                                                             |  
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.  
| 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) |
| -                              | Abnormal levels of certain  salts in the body like sodium  and potassium                                                                                                                                   |
| -                              |                                                                                                                                                                                                            |
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ccnu (lomustine)

| Possible side effects of lomustine: Common                                                                     | Occasional                                                                                                                              | Rare             |                                      |     |     |
|----------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------|------------------|--------------------------------------|-----|-----|
| Immediate:                                                                                                     | Within 1-2                                                                                                                              | Nausea, vomiting | Diarrhea, hair loss, confusion, loss |     |     |
| days of receiving drug.                                                                                        | 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               | High level of liver enzymes in the   |     |     |
| appetite                                                                                                       | 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            | Continued decrease in the number     |     |     |
| completion of treatment.                                                                                       | of white blood cells and platelets  made in the bone marrow, which  may become more of a problem  after repeated doses.                 |                  |                                      |     |     |
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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%)  
- **Gastrointestinal:** Diarrhea (1.4%)
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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**
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cefazolin adverse effects

Serious:
- **Dermatologic:** Stevens-Johnson syndrome - **Hematologic:** Leukopenia**Immunologic:** Anaphylaxis, Immune hypersensitivity reaction - **Neurologic:** Encephalopathy, Seizure
- **Renal:** Renal failure  
- **Dermatologic:** Pruritus
- **Gastrointestinal:** Diarrhea
- **Hematologic:** Drug-induced eosinophilia
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cefepime adverse effects serious

- **Dermatologic:** Stevens-Johnson syndrome, Toxic epidermal necrolysis
- **Gastrointestinal:** Pseudomembranous enterocolitis - **Immunologic:** Anaphylaxis
- **Neurologic:** Encephalopathy, Myoclonus, Seizure - **Gastrointestinal:** Clostridium difficile colitis, Pseudomembranous enterocolitis 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%)
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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%)  
- **Dermatologic:** Injection site reactions,, Rash (2.2%),
- **Gastrointestinal:** Diarrhea, Vomiting, Nausea
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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  
- **Dermatologic: Rash (0.6-1.5%)** - **Gastrointestinal:** Diarrhea (0.6% to 1.25%), Nausea (0.14% to 1.25%)
cefoxitin
adverse effects serious

- **Dermatologic:** Erythema multiforme, Stevens-Johnson syndrome - **Gastrointestinal:** Pseudomembranous enterocolitis - **Immunologic:** Anaphylaxis - **Neurologic:** Seizure Common:
- **Dermatologic:** Injection site reaction
- **Hematologic:** Thrombophlebitis
cefoxitin
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
cefoxitin
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)  
- **Hematologic:** Eosinophilia (14-32%),  
| 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                                                                                                                                                                                                                                                                                                                                                                                                 | 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                                                                                                                                                                                                                                                                                                                                                                                         | May mask fever in neutropenic  patients (L)                                                                                                                                                                                                                                                                                                                                                                                  | Upper respiratory tract                                                                                                                                                                                                                                           | Fluid retention (L), peripheral edema, GI |
| infection                                                                                                                                                                                                                                                                                                                                                                                                                                    | bleed, or bleeding from peptic ulcer disease  (L), sinusitis, pharyngitis, rhinitis                                                                                                                                                                                                                                                                                                                                          |                                                                                                                                                                                                                                                                   |                                           |
| Delayed: Any time later  during therapy,  excluding the above conditions                                                                                                                                                                                                                                                                                                                                                                     | 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:                                                                                                                                                                                                                                                                                                                                                                                                                | Mild elevation of  SGOT (AST)/SGPT  (ALT)                                                                                                                                                                                                                                                                                                                                                                                    |                                                                                                                                                                                                                                                                   |                                           |
| 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.                                                                                                                                                                                                                                                                                                                                                                                                           |                                                                                                                                                                                                                                                                                                                                                                                                                              |                                                                                                                                                                                                                                                                   |                                           |
cefoxitin
cetirizine adverse effects

Serious:
- None indicated Common:
- **Gastrointestinal:** Xerostomia - **Neurologic:** Headache, Somnolence (13.7%), Asthenia (5.2%) - **Other:** Fatigue (5.9%)
cefoxitin
cetuximab brand name(s) erbitux adverse

- **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%)  
- **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%)  
- 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.  
- specific contraindications have not been determined
cefoxitin
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
cefoxitin
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  
- **Hematologic:** Anemia, Thrombocytopenia  
| 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) |
|                                                                                                                                                                                                                             |                                                                                                                                                                                                                    |
cefoxitin
chlorothiazide

Patient should avoid activities requiring coordination until drug effects are realized, as this drug may cause dizziness or spasticity.
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.  
| 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 |
cefoxitin
chlorpromazine

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.  
Patient should not drink alcohol or use other CNS depressants while taking this drug.  
Patient should avoid exposure to organophosphorus insecticides during drug therapy.  
| 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.
cefoxitin
chlorzoxazone adverse effects serious

- **Gastrointestinal:** Gastrointestinal hemorrhage (rare) - **Hepatic:** Hepatotoxicity (rare)
- **Immunologic:** Anaphylaxis (rare)  
- **Cardiovascular:** Lightheadedness - **Neurologic:** Dizziness, Excitement, Paradoxical, Somnolence - **Other:** Malaise  
| 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%) |  
emulsion, 17%)
Conjunctival hyperemia Eye discharge Excessive tear production Pain in eye (with ophthalmic emulsion, 1-5%)
Visual disturbance (with ophthalmic emulsion, 15%)
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).
cefoxitin
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)
- **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%)  
- **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