VFEND SPECIAL INVESTIGATION FOR PROPHYLAXIS
Conditions: Fungal Infection
Sponsor: Pfizer

Vfend Special Investigation 
- For prophylaxis of invasive fungal infections in pediatric and adults –
NON-INTERVENTIONAL (NI) STUDY PROTOCOL
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STUDY INFORMATION
Title
Vfend Special Investigation
－For prophylaxis of invasive fungal infections in 
pediatric and adults－
Protocol number
A1501106
Protocol version identifier
Ver. 1.0
Date of last version of protocol
N/A
Active substance
Voriconazole
Medicinal product
Vfend 200 mg for Intravenous Use
Vfend Tablets 50 mg
Vfend Tablets 200 mg
Vfend Dry Syrup 2800 mg
Research question and objectives
This study is intended to assess the following 
items, etc. for the safety and effectiveness of Vfend 
200 mg for Intravenous Use, Vfend Tablets 50 mg, 
Vfend Tablets 200 mg, and Vfend Dry Syrup 2800 
mg (hereinafter referred to as product) in daily 
clinical practice for prophylactic administration of 
this product for invasive fungal infections in 
children and adults and review the necessity for 
further special investigation and post-marketing 
clinical study. 
- Unknown adverse reactions including those
associated with long-term use
- Occurrence of adverse reactions under actual 
clinical settings including long-term use.
- Factors considered to affect the safety and 
effectiveness of this product
Author
Post-marketing Study Strategy and Management
PMS Planning and Operation Group 1 
PPD

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TABLE OF CONTENTS
1. LIST OF ABBREVIATIONS......................................................................................................4
2. RESPONSIBLE PARTIES..........................................................................................................5
3. AMENDMENTS AND UPDATES.............................................................................................6
4. MILESTONES.............................................................................................................................6
5. RATIONALE AND BACKGROUND........................................................................................6
6. RESEARCH QUESTION AND OBJECTIVES .........................................................................7
6.1. Safety Specifications.......................................................................................................7
7. RESEARCH METHODS ............................................................................................................7
7.1. Study design ....................................................................................................................7
7.2. Setting..............................................................................................................................8
7.2.1. Inclusion criteria .................................................................................................8
7.2.2. Exclusion criteria..............................................................................................10
7.2.3. Sites for this study ............................................................................................10
7.2.4. Planned investigation period.............................................................................10
7.2.5. Study procedure................................................................................................10
7.2.6. Observation period............................................................................................10
7.3. Variables........................................................................................................................10
7.3.1. Background.......................................................................................................11
7.3.2. Targeted drug use record ..................................................................................12
7.3.3. Concomitant therapy.........................................................................................12
7.3.4. Tests..................................................................................................................12
7.3.5. Completion (discontinuation) record................................................................13
7.3.6. Effectiveness evaluation ...................................................................................13
7.3.7. Adverse events..................................................................................................14
7.3.8. Major investigation items .................................................................................14
7.4. Data sources ..................................................................................................................15
7.5. Study size ......................................................................................................................15
7.5.1. Planned sample size..........................................................................................15
7.5.2. Rationale for sample size..................................................................................15
7.6. Data management..........................................................................................................16

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7.6.1. Data collection method.....................................................................................16
7.6.2. Patient registration............................................................................................16
7.6.3. Reminders concerning completion, revision, and submission of case 
report form....................................................................................................17
7.7. Data analysis .................................................................................................................17
7.8. Quality control...............................................................................................................18
7.9. Limitations of the research methods .............................................................................18
7.10. Other aspects ...............................................................................................................18
8. PROTECTION OF HUMAN SUBJECTS ................................................................................18
8.1. Patient Information and Consent...................................................................................18
8.2. Patient withdrawal.........................................................................................................19
8.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ....................19
8.4. Ethical Conduct of the Study ........................................................................................19
9. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS .......................................................................................................................19
9.1. REQUIREMENTS........................................................................................................19
9.2. Reporting period............................................................................................................20
9.3. Causality assessment.....................................................................................................20
9.4. DEFINITIONS OF SAFETY EVENTS .......................................................................21
9.4.1. Adverse events..................................................................................................21
9.4.2. Serious adverse events......................................................................................22
9.4.3. Scenarios necessitating reporting to Pfizer Safety within 24 hours .................23
9.5. Single reference safety document..................................................................................25
10. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS..............25
11. ORGANIZATIONAL SYSTEM FOR STUDY IMPLEMENTATION.................................26
12. NAME, ADDRESS AND OUTSOURCED OPERATIONS OF THE PERSON WHO 
WAS CONTRACTED WITH THE OPERATIONS...........................................................26
13. ADDITIONAL MEASURES THAT MAY BE IMPLEMENTED BASED ON THE 
STUDY RESULTS AND CRITERIA FOR DETERMINATION OF THE 
INITIATION ........................................................................................................................26
14. SCHEDULED TIMING OF MILESTONES AND THEIR RATIONALES FOR 
REPORTING OF STUDY IMPLEMENTATION STATUS AND EVALUATION 
OF OBTAINED RESULTS TO THE PMDA .....................................................................26

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15. OTHER ASPECTS..................................................................................................................27
16. CONTACT INFORMATION..................................................................................................27
16.1. Contact information for the contents of the study.......................................................27
17. REFERENCES ........................................................................................................................27
18. LIST OF TABLES...................................................................................................................27
19. LIST OF FIGURES .................................................................................................................27
20. LIST OF STAND ALONE DOCUMENTS ............................................................................27
21. ADDITIONAL INFORMATION............................................................................................27
1. LIST OF ABBREVIATIONS
Acronym
Tittle
AE
adverse event
Al-P
Alkaline phosphatase
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
BUN
Blood urea nitrogen
CRP
C-reactive protein
EDP
exposure during pregnancy
GGT
Gamma-glutamyltransferase 
IEC
Independent Ethics Committee 
IRB
institutional review board
NIS
Non interventional study  
SRSD
Single Reference Safety Document

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2. RESPONSIBLE PARTIES
The Good Post marketing Study Practice officer
Principal Investigator(s) of the Protocol
N/A

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3. AMENDMENTS AND UPDATES
N/A
4. MILESTONES
Milestone
Planned date
Start of data collection
October 2015
End of data collection
October 2018
Final study report
To be decided
5. RATIONALE AND BACKGROUND
Vfend (nonproprietary name: voriconazole) is a new triazole therapeutic agent for invasive fungal infections
developed by Pfizer UK Central Laboratory which has a similar structure as fluconazole.
Vfend selectively acts on fungal cells and demonstrates its antimycotic action by inhibiting cytochrome P450-
dependent 14α-demethylase in the ergosterol biosynthesis which is a component of fungal cell membranes. 
Vfend 200 mg for Intravenous Use, Vfend Tablets 50 mg, and Vfend Tablets 200 mg were approved as drugs 
indicated for invasive aspergillosis, pulmonary aspergilloma, chronic necrotic pulmonary aspergillosis, 
candidemia, esophageal candidiasis*, candidal peritonitis, bronchopulmonary candidiasis, cryptococcal 
meningitis, pulmonary cryptococcosis, fusariosis, and scedosporiosis on April 11, 2005.  
Furthermore, since the options for antimycotic agents which can be used for pediatric patients are limited in 
Japan, the “Review Committee on Unapproved or Off-Labeled Drugs with High Medical Need” held in April 
2010 evaluated that the pediatric indication of voriconazole had high medical need and requested the 
development of voriconazole for pediatric use.  The pharmacokinetic study of voriconazole in pediatric 
patients was conducted in Japan and the pediatric indication of voriconazole was approved on September 26,
2014.  In so doing, since the dosage and administration in children need to be adjusted per weight and the use 
of tablets in younger children is expected to be difficult, the approval of oral dry syrup was also obtained as a 
new dosage form. 
While the prophylactic administration of antifungal agents for patients with hematopoietic stem cell 
transplantation is recommended in the domestic and overseas guidelines, considering the fact that the 
prophylactic administration of voriconazole is recommended especially for invasive aspergillosis as one of the 
options, etc., the application for additional indication for prophylaxis of deep mycosis in patients with 
hematopoietic stem cell transplantation was submitted and the approval was obtained on August 24, 2015. 
The Special Investigation of Vfend - For prophylaxis of invasive fungal infections in children and adults -
(hereinafter referred to as “This study”) will be conducted to collect information on occurrence of adverse 
reactions by Vfend 200 mg for Intravenous Use, Vfend Tablets 50 mg, Vfend Tablets 200 mg, and Vfend Dry 
Syrup 2800 mg by type of diseases, etc., quality, effectiveness and safety in daily clinical practice for 
prophylactic administration of this product for invasive fungal infections in children and adults.  The 
information collected from this study shall be used to provide proper use information and prepare documents 
for the application of re-examination.

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This study shall be conducted in strict compliance with the "Ordinance concerning Standards for Conducting 
Post-Marketing Study and Studies on Pharmaceutical products" (MHLW Ordinance No. 171 dated December
20, 2004)
Data obtained from the patients registered in this study will be reported to the MHLW pursuant to the
Pharmaceutical and Medical Device Act; pertinent to which, data may be publicly posted in MHLW's 
"Pharmaceutical and Medical Device Safety Information" and "Pharmaceuticals and Medical Devices 
Information Website (http://www.info.pmda.go.jp) as a listing of patients, which will present the names of 
drugs, adverse reactions, sex, age (increment of 10 years), and other relevant information. Furthermore, data 
collected may also be disclosed if the MHLW is required to disclose such information in accordance with the 
"Act on Access to Information Held by Administrative Organs" (Law No. 42 dated May 14, 1999) provided 
that in no event will the names of physicians, medical institutions, and other personal information be subject to 
such disclosure, nor will it be posted or disclosed in any form or shape.
*Only for tablets and dry syrup
6. RESEARCH QUESTION AND OBJECTIVES
This study is intended to assess the following items, etc. for the safety and effectiveness of Vfend 200 mg for 
Intravenous Use, Vfend Tablets 50 mg, Vfend Tablets 200 mg, and Vfend Dry Syrup 2800 mg (hereinafter 
referred to as product) in daily clinical practice for prophylactic administration of this product for invasive 
fungal infections in children and adults and review the necessity for further special investigation and post-
marketing clinical study. 
- Unknown adverse reactions including those associated with long-term use
- Occurrence of adverse reactions under actual clinical settings including long-time use
- Factors considered to affect the safety and effectiveness of this product
6.1. Safety Specifications
[Important identified risks] Hepatic toxicity, QT prolongation, ventricular tachycardia, ventricular fibrillation, 
arrhythmia, atrioventricular block complete, visual events, phototoxicity, peripheral neuropathy such as 
Guillain-Barre syndrome, renal failure, blood disorder, interstitial pneumonia, heart failure, consciousness 
disturbed
[Important potential risks] None
[Important missing information] Safety of pediatric use
7. RESEARCH METHODS
7.1. Study design
This study is a prospective multicenter cohort study conducted in patients receiving the product; for which, 
case report forms will be recorded based on data presented in medical records obtained from daily clinical 
practice.

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7.2. Setting
Patients who were administered this product for the purpose of prophylaxis of invasive fungal infections at the 
initiation of administration of this product
7.2.1. Inclusion criteria
1.
Patients who have not developed invasive fungal infections at the time of initiation of administration of
this product (patients with medical history of invasive fungal infections can be registered)
2.
Patients with history of hematopoietic stem cell transplantation or patients who plan to receive 
hematopoietic stem cell transplantation
The indications and dosage and administration of this product are as follows.  The latest package 
insert should be referred to when administering this product.
[ INDICATIONS]
Severe mycosis as follows:
- Invasive Aspergillosis, Pulmonary aspergilloma, Chronic necrotic pulmonary aspergillosis.
- Candidemea, Esophageal Candidasis*, Candidal peritonitis, Bronchopulmonary candidiasis.
- Cryptococcal meningitis, Pulmonary Cryptococcosis.
- Fusariosis.
- Scedosporiosis.                  * Only for tablets and dry syrup
Prophylaxis of invasive fungal infections in patients undergoing HSCT (Hematopoietic Stem Cell 
Transplantation)
[ DOSAGE AND ADMINISTRATION ]
<for Intravenous Use>
Adult
Voriconazole is administered by intravenous drip infusion at the 
dose of 6 mg/kg twice daily on day 1 and 3 mg/kg or 4 mg/kg 
twice daily from day 2 onward.
Children (Aged 2 to <12 and 12 ≥
whose body weight is less than 50 
kg)
9 mg/kg as voriconazole twice daily on day 1 and 8 mg/kg twice 
daily from day 2 should be given intravenously. Dose may be 
increased depending on condition of patients or if poorly 
responded by 1 mg/kg at a time, and dose in intolerant patients 
should be reduced by 1 mg/kg at a time.
Children (Aged ≥12 whose body 
weight is 50 kg or more)
6 mg/kg as voriconazole twice daily on day 1 and 4 mg/kg twice 
daily from day 2 should be given intravenously.

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<Tablet>
Adult (body weight ≥40 kg)
A recommended oral dose of voriconazole is 300 mg twice daily 
between meals on day 1, and 150 or 200 mg/dose twice daily 
between meals on day 2 and thereafter. Dose may be increased 
depending on condition of the patients or if poorly responded; 
provided that a total daily dosage should not exceed 400 
mg/dose twice daily on day 1 and 300 mg/dose twice daily on 
day 2 and thereafter. 
Adult (body weight <40 kg)
A recommended oral dose of voriconazole is 150 mg twice daily 
between meals on day 1, and 100 mg/dose twice daily between 
meals on day 2 and thereafter. Dose may be increased from day 
2 onward depending on condition of patients or if poorly 
responded; provided that a total daily dosage should not exceed 
150 mg/dose twice daily. 
Children (Aged 2 to <12 and ≥12 
whose body weight is less than 50 
kg)
After the administration of Voriconazole injection, a 
recommended maintenance oral dose of voriconazole following 
injection therapy is 9 mg/kg/dose twice daily between meals.
Dose may be increased by 1 mg/kg at a time depending on 
condition of patients or if poorly responded, and dose in 
intolerant patients should be reduced by 1 mg/kg at a time 
(unless the dosage was at its maximum 350 mg, in which case, 
dose should be reduced by 50 mg at a time). 
A total daily dosage should not exceed 350 mg/dose twice daily.
Children (Aged ≥12 whose body 
weight is 50 kg or more)
After the administration of Voriconazole injection, a 
recommended maintenance oral dose of voriconazole following 
injection therapy is 200 mg/dose twice daily between meals; 
which may be increased up to 300 mg/dose twice daily 
depending on condition of patients or if poorly responded. 
<Dry Syrup>
Adult (body weight ≥40 kg)
A recommended oral dose of voriconazole is 300 mg twice daily 
between meals on day 1, and 150 or 200 mg/dose twice daily 
between meals on day 2 and thereafter. Dose may be increased 
depending on condition of patients or if poorly responded; 
provided that a total daily dosage should not exceed 400 
mg/dose twice daily on day 1 and 300 mg/dose twice daily on 
day 2 and thereafter. 
Adult (body weight <40 kg)
A recommended oral dose of voriconazole is 150 mg twice daily 
between meals on day 1, and 100 mg/dose twice daily between 
meals on day 2 and thereafter. Dose may be increased from day 
2 onward depending on condition of patients or if poorly
responded; provided that a total daily dosage should not exceed 
150 mg/dose twice daily. 
Children (Aged 2 to <12 and ≥12 
whose body weight is less than 50 
kg)
After the administration of Voriconazole injection, a 
recommended maintenance oral dose of voriconazole following 
injection therapy is 9 mg/kg/dose twice daily between meals. 
Dose may be increased by 1 mg/kg at a time depending on 

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condition of patients or if poorly responded, and dose in 
intolerant patients should be reduced by 1 mg/kg at a time 
(unless the dosage was at its maximum 350 mg, in which case, 
dose should be reduced by 50 mg at a time). 
A total daily dosage should not exceed 350 mg/dose twice daily.
Children (Aged ≥12 whose body 
weight is 50 kg or more)
After the administration of Voriconazole injection, a 
recommended maintenance oral dose of voriconazole following
injection therapy is 200 mg/dose twice daily between meals; 
which may be increased up to 300 mg/dose twice daily 
depending on condition of patients or if poorly responded. 
7.2.2. Exclusion criteria
Patients who correspond to the following must not be registered to this study. 
- Patients who have been registered to this study before
7.2.3. Sites for this study
Sites with presence of doctors specialized in the target therapeutic area primarily in the following departments, 
at which, the product can be prescribed:
Departments of hematology, pediatrics, pediatric hematology, etc.
7.2.4. Planned investigation period
Investigation period ：October 2015 to October 2018
Registration period ：October 2015 to August 2018
(Registration will be discontinued even before the end of the registration period if the target number of patients 
is reached)
7.2.5. Study procedure
7.2.5.1. Study methods
This study will be conducted with a central registration system.
7.2.6. Observation period
The observation period shall start on the day the administration of this product begins and ends on the day the 
administration is completed; provided that the patients will be followed until the last day of the investigation
period as long as possible if the administration period prolongs. 
7.3. Variables
This study will be conducted in accordance with the following assessment schedule.

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Table 1. Schedule of observation
Timing
Variables
Baseline
Observation 
period
Termination of 
observation period
Background
ID number
●
Sex
●
Age at the time when the 
administration of the targeted drug is 
initiated
●
Height/body weight
●
Hospitalization status 
(inpatient/outpatient)
●
Objective of administration
●
History of hematopoietic stem cell 
transplantation
●
Disease history
●
Prior antifungal agents administered for 
prophylaxis of invasive fungal infections
●
Presence/absence of pregnancy
●
Targeted drug use record
●
Concomitant medications, concomitant 
medications for careful 
administration/contraindication, and 
immunosuppressants for prophylaxis of 
invasive fungal infections
●
Tests
●
Effectiveness evaluation
●
Completion (discontinuation) record
●
Confirmation of presence/absence of adverse 
events that correspond to major investigation
items (presence/absence of occurrence of 
hepatic toxicity/visual events)
●
Adverse events
●
  ●：Data items
7.3.1. Background
Input the information at the initiation of this product
(1) ID number
(2) Sex
(3) Age (at the time when the administration of the targeted drug is initiated)
(4) Height
(5) Body weight
(6) Hospitalization status (inpatient/outpatient)
(7) Objective of administration (infection for which this product is prescribed)
-Primary prophylaxis* / secondary prophylaxis** / others
*Primary prophylaxis: Prophylaxis of patients without history of fungal infection

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**Secondary prophylaxis: Prophylaxis of patients with history of fungal infection
(8) History of hematopoietic stem cell transplantation (before initiation of administration or immediately after 
initiation of this product)
- Date of hematopoietic stem cell transplantation, type of transplantation (autograft, allogeneic full 
transplantation/allogeneic mini-transplantation), source of transplantation (bone marrow/cord blood/peripheral 
stem cell)
- Occurence of GVHD (graft versus host disease)
- Disease indicated for transplantation/severity
(9) Presence/absence and severity of hepatic function disorder, renal impairment 
(10) Disease history（medical history and complications）
- Name of disease or syndrome, as well as history or pre-existing disease 
(11) Antifungal agents administered from the date of hematopoietic stem cell transplantation to the day before 
the start date of administration for prophylaxis of invasive fungal infections (name of antifungal agent, route of 
administration, reason for discontinuation)
7.3.1.1. Presence/absence of pregnancy
Input the presence/absence of pregnancy from the start date of administration until the completion of 
observation period.
7.3.2. Targeted drug use record
The following will be recorded regarding administration of this product.
(1) Dosage form 
(2) Dose
(3) Body weight used for calculation of adjustment of this product
(4) Frequency of administration
(5) Administration period
7.3.3. Concomitant therapy
7.3.3.1. Concomitant medications for prophylaxis of invasive fungal infections, mediations listed in
precautions for coadministration / contraindication for coadministration and immunosuppressants
The following information will be recorded for concomitant medications for prophylaxis of invasive fungal 
infections, concomitant medications for precautions for coadministration /contraindications for 
coadministration, and immunosuppressants from the initiation of administration of this product until the 
completion date of observation period. 
(1) Drug name (product name)
(2) Daily dose
(3) Route of administration
(4) Administration period
7.3.4. Tests
7.3.4.1. Plasma voriconazole concentration
If the plasma concentration of voriconazole was measured, input the test results.

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(1) Date and time of blood collection
(2) Date and time of administration of this product immediately before blood collection
(3) Plasma voriconazole concentration
7.3.4.2. Laboratory tests
Input the following test items and test items for adverse events. 
[Observation items] White blood cell count, neutrophil count, platelet count, total bilirubin, AST, ALT, Al-P, 
GGT, CRP, BUN, serum creatinine
7.3.5. Completion (discontinuation) record 
If the administration of this product is completed or discontinued, the reason will be recorded excluding the 
case where the administration is continued.
If an adverse event is selected for the reason, the information in detail should be recorded in the adverse event 
column.
〔Reason for completion〕
- Completion of prophylaxis
- If the objective of administration is changed from prophylaxis to treatment, completion of administration of 
this product for treatment.
〔Reason for discontinuation〕
- For the onset of invasive fungal infections
- Adverse events (other than invasive fungal infections)
- No return to hospital
- Hospital transfer
- Other
7.3.6. Effectiveness evaluation
7.3.6.1. Presence/absence of invasive fungal infections
The result of presence or absence of invasive fungal infections during the observation period will be recorded. 
If the administration with this product is continued at the completion of study period, the onset of invasive 
fungal infections until the completion of study period will be judged. 
(1) Presence/absence of onset
- Without onset
- With onset Proven diagnosis* / probable diagnosis** / Possible case*** and reason for judgment
- Underminable (reason for undeterminable)
The diagnostic criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study 
Group (EORTC/MSG) will be followed.

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*Proven diagnosis: Patients who have clinical symptoms and findings of inflammation caused by mycosis and 
the causative fungi are proved from the histological diagnosis of the focus of infection or mycological 
diagnosis from the originally sterile site, etc.
**Probable diagnosis: At least one host factor + one clinical criterion + one mycological criterion
***Possible case: At least one host factor + meeting one clinical criterion but no mycological criterion
(2) Date of onset in case of onset
(3) Name of fungal type in case of onset, sensitivity to this product
7.3.7. Adverse events
Confirm the status of adverse events from the initiation of administration of this product to the completion of 
observation period, and record the following information. Upon discovery of an adverse event, the attending 
doctor should take appropriate actions, and promptly report to Pfizer Japan Inc. (hereinafter "Sponsor"), and if 
causal relation with this product cannot be ruled out, the doctor should follow up the event until the adverse 
event or its sequelae are resolved or stabilized at the level acceptable by the attending doctor and Sponsor.
Moreover, a study should be conducted on patients in whom a serious adverse reaction, or an adverse reaction 
not specified in the package insert occurred if it is determined necessary by Sponsor.
(1) Presence/absence of adverse event
(2) Name of adverse event
(3) Date of occurrence
(4) Action
(5) Seriousness
(6) Outcome
(7) Causality
〔If the adverse event is associated with abnormal change in laboratory values, i.e., laboratory tests, the 
following information should also be recorded.〕
(1) Laboratory parameter
(2) Site reference value
(3) Unit
(4) Date of test
(5) Results
7.3.8. Major investigation items
The following items will be major investigation items in this study.
(1) Hepatic toxicity
For patients who developed events related to hepatic toxicity including abnormal hepatic function test values, 
assess the occurrence status and the differences in patient background, dose, etc. between patients who can be 
continuously administered this product and patients who must be discontinued administration of this product. 
(2) Visual events
Set the presence or absence of visual events as an investigation item.  Assess the occurrence status for patients 
who developed visual events and the differences in patient background, dose, etc. between patients who can be 

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continuously administered with this product and patients who must be discontinued administration of this 
product.
7.3.8.1. Confirmation of presence/absence of adverse events that correspond to  major investigation 
items
7.3.8.1.1. Presence/absence of hepatic toxicity
The presence/absence of hepatic toxicity including hepatitis, jaundice, hepatic failure, coma hepatic, ALT 
(GPT) increased, AST (GOT) increased, and GGT increased should be recorded for target patients in this study.  
If aggravation or new occurrence of hepatic toxicity is observed, the information in detail should be recorded 
in the adverse event column.
7.3.8.1.2. Presence/absence of occurrence of visual events
The presence/absence of aggravation or new occurrence of visual events including photophobia, vision blurred, 
and visual disturbance should be recorded for target patients in this study. If aggravation or new occurrence of 
visual event is observed, the information in detail should be recorded in the adverse event column.
7.4. Data sources
In this study, the investigators extract the necessary information from the medical record in accordance with 
the protocol.
7.5. Study size
7.5.1. Planned sample size
200 patients (100 patients each for children and adults)
7.5.2. Rationale for sample size
It was considered that the following evaluations were possible if the target sample size was set to be 200 
patients in total; 100 patients each for children and adults. 
Safety perspectives:
In the phase 3 study of prophylactic administration of Vfend in foreign patients with HSCT (study A1501073), 
the incidence of adverse reactions classified into the SOC of hepatobiliary disorders was 20.2% (47/233 
patients). Of those, one patient was led to discontinuation of administration of this product.  In the phase 3 
study of secondary prophylactic administration of Vfend in foreign patients with HSCT (study A1501038), the 
incidence of adverse reactions classified into the SOC of hepatobiliary disorders was 24.4% (11/45 patients). 
Of those, two patients were led to discontinuation of this product.  Also, in the clinical study of Vfend 
conducted in Japanese children (from 2 years old to under 15 years old) (study A1501096), the incidence of 
adverse reactions related to hepatic toxicity including abnormal hepatic function test values was 19.0% (4/21 
patients). Of those, two patients were led to discontinuation of this product.  Based on the above, the incidence 
of hepatic toxicity in patients administered this product for prophylaxis of invasive fungal infections was 
similar between Japanese and foreign patients and it was considered that such incidence was also similar 
between adults and children. 

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In the case where the number of patients to be collected for the special investigation for prophylactic 
administration of Vfend for invasive fungal infections is set to be 200 patients and the incidence of hepatic
toxicity is presumed to be 20%, it is estimated that at least 31 patients with hepatic toxicity will be 
accumulated at a probability of about 95%.  With the cumulation of this sample size, it was considered 
possible to compare and review the proportion of patients who discontinued the administration of this product 
with the clinical studies. 
Although the incidence of visual events varies among different studies (study A1501073: 12.0%, study 
A1501038: 4.4%, and study A1501096: 42.9%), if it is presumed that there is the incidence of 5% or higher, 
the expected value of the incidence to be observed in 200 patients will be at least 10 patients.  While it is 
possible that there may be no patient who discontinues the administration of this product due to visual events 
based on the results of clinical studies, if any patient who discontinues the administration of this product is 
observed, how it happened will be examined. 
Effectiveness perspectives: 
The successful rate of prophylaxis at Day 100 in the phase 3 study of prophylactic administration (study 
A1501073) was 54.3% (121/223 patients) and the successful rate of prophylaxis at Day 180 was 48.9% 
(109/223 patients). Presuming that the 50% prophylactic effect can be obtained at Day 180 by referring to the 
above results, the 95% CI will be 40 - 60% if the target sample size is set to be 100 patients and 43-57% if the 
target sample size is set to be 200 patients.  The prophylactic effect can be confirmed at the estimate accuracy 
of about ±10% if 100 patients for whom this product is administered for prophylaxis of invasive fungal 
infections are accumulated and that of about ±7% if 200 patients are accumulated. 
7.6. Data management
7.6.1. Data collection method
Data for this study shall be collected using a specific case report form provided by Sponsor. Investigator will 
complete promptly after observation period and submit them to the Sponsor.
7.6.2. Patient registration
7.6.2.1. Procedure of patient registration
(1) Registration
The following information regarding registration should be recorded in the registration forms if this product is 
given to patients who meet the following registration criteria; patients should be registered via FAX at the 
registration center until the target number of patients is registered. Patients should be registered via FAX 
within 2 weeks from the initiation of administration of this product with the start date of administration as Day 
1.
1) Registration criteria
- Patients who have not developed invasive fungal infection at the initiation of administration with this product
- Patients who received hematopoietic stem cell transplantation or patients who plan to receive hematopoietic 
stem cell transplantation
2) Registration data

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Patient identification number, sex, age at the initiation of administration, date on which administration of this 
product begins and eligibility to registration criteria
(2) Exclusion from the registration
Patients found to not meet the registration criteria after the registration form is received at the registration 
center will be excluded from the registration.
7.6.3. Reminders concerning completion, revision, and submission of case report form
7.6.3.1. Completion
The investigator shall, upon confirming the study items, complete the CRF based on medical charts and other 
medical records such as relevant test results, using an ineffaceable ink such as ballpoint pen.
7.6.3.2. Revision
Upon receiving Sponsor's inquiry on the contents of the CRF (query forms), the investigator will again confirm 
the contents of medical records described earlier, and as required, correct relevant sections and resubmit the 
form. Corrections in the CRF should be struck out with a double line (=) with a "correction seal" on the double 
line; the double line should be drawn so that the original contents prior to correction are legible.
7.6.3.3. Submission
CRFs should be submitted promptly upon completion in accordance with the procedures set out by Sponsor.
7.7. Data analysis
The details of analysis method on data collected in this study shall be described in the Statistical Analysis Plan 
to be separately prepared.
1) Definition of analysis set
The safety analysis set shall include patients for whom the registration in this study and administration of this 
product have been confirmed and the safety has been evaluated.
The effectiveness analysis set shall include patients for whom the presence/absence of invasive fungal 
infections has been evaluated among the safety analysis set.
2) Analysis method
(1) Safety analysis
[ Patient Registration Center ]
FAX No.:  0120－007－233 （Accessible 24 hours a day）

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The number of patients who developed each adverse reaction and the proportions will be tabulated.  Also, for 
patients who developed major investigation items of hepatic toxicity and visual events, differences between 
patients who can continuously receive this product and patients who must discontinue the administration of
this product will be analyzed experimentally. 
(2) Effectiveness analysis
The proportion of patients who developed invasive fungal infections (the number of patients with proven 
diagnosis + the number of patients with probable diagnosis/number of patients for effectiveness analysis 
excluding undeterminable patients × 100), proportion of patients with successful prophylaxis of invasive 
fungal infections (the number of patients without onset of invasive fungal infections/the number of patients for 
effectiveness analysis excluding undeterminable patients × 100), and each 95% CI will be calculated for
effectiveness analysis set.  Also, the analysis using the survival analysis method (Kaplan-Meier method) will 
be performed. 
Detailed methodology for summary and statistical analyses of data collected in this study will be documented
in a Statistical Analysis Plan (SAP), which will be dated, filed and maintained by the Sponsor. The SAP may 
modify the plans outlined in the protocol; any major modifications of primary endpoint definitions or their 
analyses would be reflected in a protocol amendment.
7.8. Quality control
Pfizer staff in charge of site will explain the contents of the protocol, etc. to the investigator prior to the 
implementation of this study and ask the investigator to prepare a case report form based on medical charts.
7.9. Limitations of the research methods
The following matters are considered for this study:
1) Since no control group is set in the study, there is a limit to the judgment on whether or not a risk of 
developing adverse events and adverse reactions increases due to the administration of the study drug.
2) The consideration for confounding factors may not be adequate because the background information may 
not be sufficiently obtained.
3) Since this is a study that collects the information described in medical charts, the set data may not be 
collected or there may be missing information.
7.10. Other aspects
N/A
8. PROTECTION OF HUMAN SUBJECTS
8.1. Patient Information and Consent
All parties will ensure protection of patient personal data and will not include patient names on any sponsor 
forms, reports, publications, or in any other disclosures, except where required by laws. In case of data transfer, 
Pfizer will maintain high standards of confidentiality and protection of patient personal data.

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In this study, the information will be collected by transcribing medical chart information described in routine 
medical practice. In doing so, the informed consent will not be used because the information collected from 
medical charts is anonymized and does not contain any information that identifies individual patients.
8.2. Patient withdrawal
Patients may withdraw from the study at any time at their own request, or they may be withdrawn at any time 
at the discretion of the investigator or sponsor for safety, behavioral, or administrative reasons.  In any 
circumstance, every effort should be made to document outcome, if possible.  The investigator should inquire 
about the reason for withdrawal and follow-up with the patient regarding any unresolved adverse events.  
8.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
In this study, the review by the IRB/IEC is not essential.
8.4. Ethical Conduct of the Study
This study is excluded from the patient since it includes the scope of application of the “Good Post-Marketing 
Study Practice” (Ordinance of Ministry of Health, Labour and Welfare No. 171 of December 20, 2004)
9. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE REACTIONS
The handling of each event in the case where the investigator becomes aware of any event concerning the 
safety information should be prescribed as follows:
For an event that needs to be reported to the Sponsor within 24 hours, the investigator must report it using the 
designated “Non Interventional study AE Report Form (hereinafter referred to as “NIS AE Report Form”).
At the initiation of study, each staff in charge of each site shall request each investigator to report events that 
need to be reported within 24 hours of discovery, and visit the investigator periodically within the study period 
to request for reporting.
The NIS AE Report Form will be handled as part of the case report form.
9.1. REQUIREMENTS
The table below summarizes the requirements for recording safety events on the case report form and for 
reporting safety events on the non-interventional study (NIS) adverse event monitoring (AEM) Report Form to 
Pfizer Safety. These requirements should be described for the following 3 types of events.(1) serious adverse 
events (SAEs); (2) non-serious AEs (as applicable); and (3) scenarios involving exposure to a Pfizer product, 
including exposure during pregnancy, exposure during breast feeding, medication error, overdose, misuse, 
extravasation, and occupational exposure. These events are defined in the section “Definitions of safety 
events”.  
Safety event
Recorded on the case report 
form 
Reported on the NIS AEM
Report Form to Pfizer Safety 
within 24 hours of awareness
SAE
All
All
Non-serious AE
All
None

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Safety event
Recorded on the case report 
form 
Reported on the NIS AEM
Report Form to Pfizer Safety 
within 24 hours of awareness
Scenarios involving exposure to a 
Pfizer product, including exposure 
during pregnancy, exposure during 
breast feeding, medication error, 
overdose, misuse, extravasation; lack 
of efficacy; and occupational exposure
All (regardless of whether associated 
with an AE), except occupational 
exposure
All (regardless of whether 
associated with an AE) involving 
exposure to a Pfizer product
For each AE, the investigator must pursue and obtain information adequate both to determine the outcome of 
the adverse event and to assess whether it meets the criteria for classification as a SAE (see section "Serious 
Adverse Events” below)
Safety events must be reported to Pfizer within 24 hours of awareness of the event by the investigator as 
described in the table above. In particular, if the SAE is fatal or life-threatening, notification to Pfizer must be
made immediately, irrespective of the extent of available event information. This timeframe also applies to 
additional new (follow-up) information on previously forwarded safety event reports. In the rare situation that 
the investigator does not become immediately aware of the occurrence of a safety event, the investigator must 
report the event within 24 hours after learning of it and document the time of his/her first awareness of the 
events.
For those safety events that are considered serious or that are identified in the far right column of the table 
above that are reportable to Pfizer within 24 hours of awareness, the investigator is obligated to pursue and to 
provide any additional information to Pfizer in accordance with this 24-hour timeframe. In addition, an
investigator may be requested by Pfizer to obtain specific follow-up information in an expedited fashion. This 
information is more detailed than that recorded on the case report form. In general, this will include a 
description of the adverse event in sufficient detail to allow for a complete medical assessment of the case and 
independent determination of possible causality. Information relevant to the event, such as concomitant 
medications and illnesses must be provided. In the case of a patient death, a summary of available autopsy
findings must be submitted as soon as possible to Pfizer or its designated representative. 
9.2. Reporting period
For each patient, the safety event reporting period begins at the time of the patient’s first dose of this product, 
and lasts through the end of the observation period of the study, which must include at least 28 calendar days 
following the last administration of a drug under study; a report must be submitted to Pfizer Safety (or its 
designated representative) for any of the types of safety events listed in the table above occurring during this 
period. If a patient was administered a drug under study on the last day of the observation period, then the 
reporting period should be extended for 28 calendar days following the end of observation.
If the investigator becomes aware of a SAE occurring at any time after completion of the study and s/he 
considers the SAE to be related to this product, the SAE also must be reported to Pfizer Safety. 
9.3. Causality assessment
The investigator is required to assess and record the causal relationship. For all AEs, sufficient information 
should be obtained by the investigator to determine the causality of each adverse event. For AEs with a causal 

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relationship to this product, follow-up by the investigator is required until the event and/or its sequelae resolve 
or stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.  
An investigator’s causality assessment is the determination of whether there exists a reasonable possibility that 
this product caused or contributed to an adverse event. If the investigator’s final determination of causality is 
“unknown” and s/he cannot determine whether this product caused the event, the safety event must be reported 
within 24 hours.  
If the investigator cannot determine the etiology of the event but s/he determines that this product did not cause 
the event, this should be clearly documented on the case report form and the NIS AEM Report Form. 
9.4. DEFINITIONS OF SAFETY EVENTS
9.4.1. Adverse events
An AE is any untoward medical occurrence in a patient administered a medicinal product. The event need not 
necessarily have a causal relationship with the product treatment or usage. Examples of adverse events include 
but are not limited to:  
･Abnormal test findings (see below for circumstances in which an abnormal test finding constitutes an 
adverse event);
･Clinically significant symptoms and signs;
･Changes in physical examination findings;
･Hypersensitivity;
･Progression/worsening of underlying disease;
･Lack of efficacy;
･Drug abuse;
･Drug dependency.
Additionally, for medicinal products, they may include the signs or symptoms resulting from:
･Drug overdose;
･Drug withdrawal;
･Drug misuse; 
･Off-label use; 
･Drug interactions;
･Extravasation;
･Exposure during pregnancy;
･Exposure during breast feeding;
･Medication error;
･Occupational exposure.
Abnormal test findings
The criteria for determining whether an abnormal objective test finding should be reported as an adverse event 
are as follows: 

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･Test result is associated with accompanying symptoms, and/or
･Test result requires additional diagnostic testing or medical/surgical intervention, and/or
･Test result leads to a change in study dosing or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy, and/or
･Test result is considered to be an adverse event by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not constitute an 
adverse event. Any abnormal test result that is determined to be an error does not require reporting as an 
adverse event.
9.4.2. Serious adverse events
A serious adverse event is any untoward medical occurrence in a patient administered a medicinal or
nutritional product (including pediatric formulas) at any dose that:
･Results in death;
･Is life-threatening;
･Requires inpatient hospitalization or prolongation of hospitalization (see below for circumstances that 
do not constitute adverse events);
･Results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct 
normal life functions);
･Results in congenital anomaly/birth defect.
Medical and scientific judgment is exercised in determining whether an event is an important medical event. 
An important medical event may not be immediately life-threatening and/or result in death or hospitalization. 
However, if it is determined that the event may jeopardize the patient or may require intervention to prevent 
one of the other outcomes listed in the definition above, the important medical event should be reported as 
serious.
Examples of such events are intensive treatment in an emergency room or at home for allergic bronchospasm; 
blood dyscrasias or convulsions that do not result in hospitalization; or development of drug dependency or
drug abuse.
Additionally, any suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-
pathogenic, is considered serious. The event may be suspected from clinical symptoms or laboratory findings 
indicating an infection in a patient exposed to a Pfizer product. The terms “suspected transmission” and 
“transmission” are considered synonymous. These cases are considered unexpected and handled as serious 
expedited cases by PV personnel. Such cases are also considered for reporting as product defects, if 
appropriate.
Hospitalization
Hospitalization is defined as any initial admission (even if less than 24 hours) to a hospital or equivalent 
healthcare facility or any prolongation to an existing admission. Admission also includes transfer within the 
hospital to an acute/intensive care unit (e.g., from the psychiatric wing to a medical floor, medical floor to a 
coronary care unit, neurological floor to a tuberculosis unit). An emergency room visit does not necessarily 
constitute a hospitalization; however, an event leading to an emergency room visit should be assessed for 
medical importance. 

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Hospitalization in the absence of a medical AE is not in itself an AE and is not reportable. For example, the 
following reports of hospitalization without a medical AE are not to be reported. 
･Social admission (e.g., patient has no place to sleep)
･Administrative admission (e.g., for yearly exam)
･Optional admission not associated with a precipitating medical AE (e.g., for elective cosmetic surgery)
･Hospitalization for observation without a medical AE
･Admission for treatment of a pre-existing condition not associated with the development of a new AE 
or with a worsening of the pre-existing condition (e.g., for work-up of persistent pre-treatment lab 
abnormality)
･Protocol-specified admission during clinical study (e.g., for a procedure required by the study protocol)
9.4.3. Scenarios necessitating reporting to Pfizer Safety within 24 hours
Scenarios involving exposure during pregnancy, exposure during breastfeeding, medication error, overdose, 
misuse, extravasation, lack of efficacy, and occupational exposure are described below.
Exposure during pregnancy;
An exposure during pregnancy (EDP) occurs if:
1. A female becomes, or is found to be, pregnant either while receiving or having been exposed to (e.g., 
environmental) this product, or the female becomes, or is found to be, pregnant after discontinuing 
and/or being exposed to this product (maternal exposure). 
An example of environmental exposure would be a case involving direct contact with a Pfizer product in 
a pregnant woman (e.g., a nurse reports that she is pregnant and has been exposed to chemotherapeutic 
products).
2. A male has been exposed, either due to treatment or environmental exposure to this product prior to or 
around the time of conception and/or is exposed during the partner pregnancy (paternal exposure). 
As a general rule, prospective and retrospective exposure during pregnancy reports from any source are 
reportable irrespective of the presence of an associated AE and the procedures for SAE reporting should be 
followed.
If a study participant or study participant’s partner becomes, or is found to be, pregnant during the study 
participant’s treatment with this product, this information must be submitted to Pfizer, irrespective of whether 
an adverse event has occurred, must be submitted using the NIS AEM Report Form and the EDP Supplemental 
Form. 
In addition, the information regarding environmental exposure to this product, in a pregnant woman (e.g., a 
subject reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or spillage) must 
be submitted using the NIS AEM Report Form and the EDP supplemental form. This must be done
irrespective of whether an AE has occurred.  
Information submitted should include the anticipated date of delivery (see below for information related to 
termination of pregnancy).

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Follow-up is conducted to obtain general information on the pregnancy, in addition, follow-up is conducted to 
obtain information on EDP outcome for all EDP reports with pregnancy outcome unknown. A pregnancy is 
followed until completion or until pregnancy termination (e.g., induced abortion) and Pfizer is notified of the 
outcome. This information is provided as a follow up to the initial EDP report. In the case of a live birth, the 
structural integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test findings are 
conclusive for a congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (e.g., ectopic pregnancy, spontaneous abortion, 
intrauterine fetal demise, neonatal death, or congenital anomaly [in a live born, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death]), the procedures for reporting SAEs should be followed.
Additional information about pregnancy outcomes that are reported as SAEs follows: 
･Spontaneous abortion includes miscarriage and missed abortion;
･Neonatal deaths that occur within 1 month of birth should be reported, without regard to causality, as 
SAEs. In addition, infant deaths after 1 month should be reported as SAEs when the investigator assesses 
the infant death as related or possibly related to exposure to investigational product
Additional information regarding the exposure during pregnancy may be requested. Further follow-up of birth 
outcomes will be handled on a case-by-case basis (e.g., follow-up on preterm infants to identify developmental 
delays).  
In the case of paternal exposure, the study participant will be provided with the Pregnant Partner Release of 
Information Form to deliver to his partner. It must be documented that the study participant was given this 
letter to provide to his partner.
Exposure during breastfeeding;
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of an associated AE. 
An exposure during breastfeeding report is not created when a Pfizer drug specifically approved for use in 
breastfeeding women (e.g., vitamins) is administered in accord with authorized use. However, if the infant 
experiences an AE associated with such a drug’s administration, the AE is reported together with the exposure 
during breastfeeding.
Medication error;
A medication error is any unintentional error in the prescribing, dispensing or administration of a medicinal 
product that may cause or lead to inappropriate medication use or patient harm while in the control of the 
health care professional, patient, or consumer. Such events may be related to professional practice, health care 
products, procedures, and systems including: prescribing; order communication; product labeling, packaging, 
and nomenclature; compounding; dispensing; distribution; administration; education; monitoring; and use.
Medication errors include:
･Near misses, involving or not involving a patient directly (e.g., inadvertent/erroneous administration, 
which is the accidental use of a product outside of labeling or prescription on the part of the healthcare 

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provider or the patient/consumer);
･Confusion with regard to invented name (e.g., trade name, brand name).
The investigator must submit the following medication errors to Pfizer, irrespective of the presence of an 
associated AE/SAE :
･Medication errors involving patient exposure to the product, whether or not the medication error is 
accompanied by an AE.
･Medication errors that do not involve a patient directly (e.g., potential medication errors or near 
misses). When a medication error does not involve patient exposure to the product the following 
minimum criteria constitute a medication error report:
･An identifiable reporter;
･A suspect product;
･The event medication error.
Overdose, Misuse, Extravasation
Reports of overdose, misuse, and extravasation associated with the use of a Pfizer product are reported to 
Pfizer by the investigator, irrespective of the presence of an associated AE/SAE.
Lack of efficacy;
Reports of lack of efficacy to a Pfizer product are reported to Pfizer by the investigator, irrespective of the 
presence of an associated AE/SAE or the indication for use of the Pfizer product.
Occupational exposure.
Reports of occupational exposure to a Pfizer product are reported to Pfizer by the investigator, irrespective of 
the presence of an associated AE/SAE.
9.5. Single reference safety document
A Single Reference Safety Document (SRSD) refers to a document that contains the information on the known 
safety profile. The package insert of this product will be the SRSD in this study. Pfizer Japan Inc. will evaluate 
the safety information reported by the investigator during the study period using the SRSD.
The investigator will also prescribe the drug and give the drug administration guidance based on the SRSD.
10. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
The study results may be published during scientific meetings, in research paper, etc. for the purpose of 
providing proper use information, etc.
COMMUNICATION OF ISSUES
In the event of any prohibition or restriction imposed (e.g., clinical hold) by an applicable Competent 
Authority in any area of the world, or if the investigator is aware of any new information which might 
influence the evaluation of the benefits and risks of a Pfizer product, Pfizer should be informed immediately.

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In addition, the investigator will inform Pfizer immediately of any urgent safety measures taken by the 
investigator to protect the study patients against any immediate hazard, and of any serious breaches of this NI 
study protocol that the investigator becomes aware of.
11. ORGANIZATIONAL SYSTEM FOR STUDY IMPLEMENTATION
The organizational system in this study is equivalent to that for the operations such as the risk management 
plan and post-marketing study.  The director of the Post Marketing Study Strategy and Management will be 
responsible for post-marketing study.
12. NAME, ADDRESS AND OUTSOURCED OPERATIONS OF THE PERSON WHO WAS 
CONTRACTED WITH THE OPERATIONS
1) Subcontractors
(1) Registration center
Company name: EP Pharma Line Co., Ltd.
Address: 3-27-12 Nishi-Ikebukuro, Toshima-ku, Tokyo
(2) Destination of case report and query forms, data management, and statistical analysis
Company name: EPS Corporation
Address: 8F Acropolis TOKYO, 6-29 Shinogawamachi, Shinjuku-ku, Tokyo
2) Scope of subcontract
Activities concerning registration center, destination of case report and query forms, data management, 
and statistical analysis, except for management activities.
13. ADDITIONAL MEASURES THAT MAY BE IMPLEMENTED BASED ON THE STUDY 
RESULTS AND CRITERIA FOR DETERMINATION OF THE INITIATION
The Drug Risk Management Plan should be reviewed and revised as necessary at each relevant milestone for 
the contents including the following information. 
The necessity to amend the protocol of this study including presence/absence of new safety specifications 
should be discussed. 
The necessity of risk minimization plan including that for new safety specifications should be discussed. 
14. SCHEDULED TIMING OF MILESTONES AND THEIR RATIONALES FOR REPORTING OF 
STUDY IMPLEMENTATION STATUS AND EVALUATION OF OBTAINED RESULTS TO THE 
PMDA
[Planned milestone]
At the time of Periodic Safety Report
[Rationale]
To comprehensively evaluate the safety information

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15. OTHER ASPECTS
1）Amendment of the protocol
Based on the new knowledge to be obtained according to the progress of this study, the need for amendment of 
the protocol will be examined and the protocol will be amended if necessary.  Also, the need for amendment of 
the protocol will be examined and the protocol will be amended even if the partial change in the dosage and 
administration or indication is approved during the reexamination period (except the case when the 
reexamination period is newly designated), etc.
2）Actions to be taken if any problem or question is observed
In the cases where the onset of any serious and unknown adverse reaction is suggested, a significant increase in 
the frequency of adverse reactions is observed, any problem is found in the effectiveness and safety of the drug 
compared to those prior to the approval, the onset of a different kind of adverse reaction is suggested, etc., the 
amendment of the package insert and implementation of a new special investigation or post-marketing clinical 
study should be considered.
16. CONTACT INFORMATION
16.1. Contact information for the contents of the study
Name
Pfizer Japan Inc. Post Marketing Study Strategy and Management 
Department
Address
Shinjuku Bunka Quint Building 3-22-7 Yoyogi Shibuya-ku, Tokyo 151-
8589
E-mail address
VFD-yobouPMS@pfizer.com
17. REFERENCES
None.
18. LIST OF TABLES
・Page11.  Table 1. Schedule of observation
19. LIST OF FIGURES
N/A
20. LIST OF STAND ALONE DOCUMENTS
N/A
21. ADDITIONAL INFORMATION
N/A