Guidance for Industry 
and FDA Staff 
 
Dear Health Care Provider 
Letters:  Improving 
Communication of Important 
Safety Information 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
 
January 2014 
Procedural 
 
 
OMB Control No. 0910-0754 
Current expiration date available at https://www.reginfo.gov  
(Search ICR and enter OMB control number 0910-0754) 
See additional PRA statement in section VII of this guidance. 
 
201181fnlPRAupdate10/31/22   
Guidance for Industry 
and FDA Staff 
 
Dear Health Care Provider 
Letters:  Improving 
Communication of Important 
Safety Information 
 
Additional copies are available from: 
Office of Communications 
Division of Drug Information, WO51, Room 2201 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10903 New Hampshire Ave., Silver Spring, MD 20993  
Phone: 301-796-3400; Fax: 301-847-8714 
druginfo@fda.hhs.gov  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
and/or 
 Office of Communication, Outreach and  
Development, HFM-40  
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
1401 Rockville Pike, Rockville, MD 20852-1448  
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm   
(Tel) 800-835-4709 or 301-827-1800 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
January 2014 
Procedural 
 
 
  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  FDA CONSULTATION ON DEVELOPMENT OF DHCP LETTERS ..................... 2 
IV.  WHEN TO USE A DHCP LETTER AND WHICH TYPE OF DHCP LETTER TO 
USE ..................................................................................................................................... 3 
A.  Important Drug Warning Letters ................................................................................................ 3 
B.  Important Prescribing Information Letters ................................................................................ 4 
C.  Important Correction of Drug Information Letters ................................................................... 4 
V.  CONTENT AND FORMAT OF DHCP LETTERS ...................................................... 5 
A.  Content Recommendations ........................................................................................................... 5 
B.  Format Recommendations .......................................................................................................... 10 
VI.  ASSESSMENT OF THE DHCP LETTER IMPACT ................................................. 10 
VII.  PAPERWORK REDUCTION ACT OF 1995 .............................................................. 11 
APPENDIX A:  IMPORTANT DRUG WARNING - MODEL LETTER ............................ 12 
APPENDIX B:  IMPORTANT PRESCRIBING INFORMATION - MODEL LETTER ... 14 
APPENDIX C:  CORRECTION OF DRUG INFORMATION - MODEL LETTER ......... 16 
i 
  Contains Nonbinding Recommendations 
 
Guidance for Industry and FDA Staff1 
 
Dear Health Care Provider Letters: 
Improving Communication of Important Safety Information 
 
 
 
This guidance represents the Food and Drug Administrations (FDAs) current thinking on this topic.  It 
does not create or confer any rights for or on any person and does not operate to bind FDA or the public.  
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 
and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for 
implementing this guidance.  If you cannot identify the appropriate FDA staff, call the appropriate 
number listed on the title page of this guidance.  
 
 
 
I.  INTRODUCTION  
 
This guidance provides recommendations to industry and FDA staff on the content and format of 
Dear Health Care Provider (DHCP) letters.2  DHCP letters are correspondence  often in the 
form of a mass mailing from the manufacturer or distributor of a human drug or biologic or from 
FDA  intended to alert physicians and other health care providers about important new or 
updated information regarding a human drug or biologic (hereafter drug and product refer to 
both biologic and small molecule drug products).  DHCP letters may also be distributed by email 
and are often made available on the Internet (e.g., on company Web sites or through patient 
advocacy groups).  This guidance provides recommendations on (1) when to issue a DHCP 
letter, (2) the types of information to include in a DHCP letter, (3) how to organize that 
information so that it is communicated effectively to health care providers, and (4) formatting 
techniques to make the information more accessible.  
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agencys current thinking on a topic and should 
be viewed only as recommendations, unless specific regulatory or statutory requirements are 
cited.  The use of the word should in Agency guidances means that something is suggested or 
recommended, but not required.  
 
 
 
1 This guidance has been prepared by the Office of Medical Policy in the Center for Drug Evaluation and Research 
(CDER) and the Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration.  
2 The concepts provided in this guidance may be used, in appropriate circumstances, to help develop correspondence 
to meet certain communication plan requirements for Risk Evaluation and Mitigation Strategies (REMS) under 
section 505-1(e)(3) of the Federal Food, Drug, and Cosmetic Act.   
  1  Contains Nonbinding Recommendations 
 
II.  BACKGROUND 
 
New or updated information about drug products emerges throughout a products life cycle.  For 
marketed products, there are occasions when it is important to communicate this information 
promptly to health care providers involved in prescribing or dispensing a drug or in caring for 
patients who receive a drug.  The DHCP letter is one of the mechanisms used to communicate 
important new information about a marketed product.  FDA regulations describe the process for 
mailing important new information about drug products (21 CFR 200.5), but do not provide 
instructions on the format and content of the actual letter.  Nor do the regulations provide 
information on electronic or other means of communication.   
 
Formal and informal evaluations of DHCP letters have shown that the communication quality of 
these letters  the extent to which the information is accessible and can be understood  has 
varied widely.  A 2005 study (the Mazor study) evaluated the quality of a group of DHCP letters 
sent during 2000 and 2001 that were intended to communicate important new drug safety 
information.3  The Mazor study found a correlation between the quality or perceived quality of a 
DHCP letter and the extent to which physicians perceived the new information as important.  
Letters that were evaluated as clearer, more concise, better organized and formatted and that 
focused on the most important aspects of the new safety information were considered more 
effective in communicating the new information. 
 
FDA therefore believes that guidance on the format and content of the DHCP letter would help 
improve the effectiveness of DHCP letters in communicating drug information.  This guidance 
provides recommendations intended to improve the quality of DHCP letters and enhance the 
communication of important drug information.  These recommendations are based on some of 
the findings and recommendations from the Mazor study, FDAs own experience in evaluating 
DHCP letters, and the Agencys general risk communication experience. 
 
III.  FDA CONSULTATION ON DEVELOPMENT OF DHCP LETTERS 
 
FDA believes that effective communication of important new information in DHCP letters can 
best be accomplished if FDA and the manufacturer work together to determine: 
 
  Whether a DHCP letter should be used to convey new information 
  How to present the new information in the DHCP letter 
  The target audience for the information in the DHCP letter 
  The time frame for distributing the DHCP letter 
 
FDA encourages manufacturers to consult with the appropriate review division (e.g., the Offices 
of Drug Evaluation within the Office of New Drugs, the Office of Generic Drugs) during the 
development of a DHCP letter to ensure that the letter clearly and accurately reflects both the 
manufacturers and FDAs understanding of the issue and the action required.  In addition to 
 
3 Mazor KM, Andrade SE, Auger J, Fish L, Gurwitz JH, 2005, Communicating Safety Information to Physicians:  
An Examination of Dear Doctor Letters, Pharmacoepidemiol Drug Saf, 14 (12):869-875. 
  2  Contains Nonbinding Recommendations 
 
providing a broader range of input into the content of the letter, such consultation could help 
ensure FDAs concurrence that the content of the letter is not in some way false or misleading.  
 
Discussion with the appropriate FDA review division should also address the intended target 
audience(s) for the DHCP letter so the letter can be directed more selectively to those health care 
providers (and their professional societies) who need the information.  For example, a DHCP 
letter describing a product used to treat Alzheimers disease should be sent to neurologists, 
psychiatrists, geriatricians, and internists.  A DHCP letter describing a recommended action for 
pharmacists should be directed to pharmacists; a letter describing revised safety information and 
use instructions for dialysis patients should be distributed to dialysis centers and nephrologists.  
Further, the means by which the letter will be distributed (e.g., mass mailing, electronic 
distribution) should be discussed.  
 
The planned time frame for distributing the letter to the target audience should be determined 
through discussion between the manufacturer and the FDA review division so that the intended 
audience receives the information promptly, as appropriate to the issue being communicated.  
 
IV.  WHEN TO USE A DHCP LETTER AND WHICH TYPE OF DHCP LETTER TO 
USE 
 
When is a DHCP Letter Needed? 
 
In general, a DHCP letter is used to notify health care providers about important new or updated 
information about a drug.  In most cases, the information relates to an important safety concern 
that could affect the decision to use a drug or require some change in behavior by health care 
providers, patients, or caregivers to reduce the potential for harm from a drug.  Some DHCP 
letters are written as part of Risk Evaluation and Mitigation Strategies (REMS) communication 
programs to inform intended target audiences about the implementation of a new or modified 
REMS or to present additional required safety information about the product.  In some cases, a 
DHCP letter provides information on how to improve the effectiveness of a drug or information 
about drug shortage issues.  A DHCP letter also may be needed to correct misleading 
information in advertising or other types of prescription drug promotion.   
 
Three types of DHCP letters are specifically described in FDA regulations (21 CFR 200.5): 
Important Drug Warning Letters, Important Prescribing Information Letters, and Important 
Correction of Drug Information Letters.  As described in the previous paragraph, DHCP letters 
relating to other topics (e.g., REMS, drug shortages) may use the concepts and recommendations 
from this guidance. 
 
A.  Important Drug Warning Letters 
 
Important Drug Warning letters are used to convey important new safety information that 
concerns a significant hazard to health (21 CFR 200.5(c)(1)) and therefore could affect the 
decision to use a drug or require a change in behavior concerning use of the drug (e.g., a specific 
type of monitoring).  This type of DHCP letter is used to convey information that is being 
incorporated into one or more of the following sections of the prescribing information:  BOXED 
  3  Contains Nonbinding Recommendations 
 
WARNINGS, CONTRAINDICATIONS, or WARNINGS AND PRECAUTIONS.  Examples of 
the types of safety concerns that are communicated in Important Drug Warning letters include, 
but are not limited to, the following: 
 
  Previously unknown serious or life-threatening adverse reactions 
  Clinically important new information about a known adverse reaction 
  Identification of a subpopulation at greater risk in whom the drug should be used 
with added caution (e.g., patients with renal or hepatic failure, HIV+ patients) 
  Identification of a subpopulation in which the drug is contraindicated  
  A drug interaction or medication error that may result in a serious or life-
threatening adverse reaction 
  Implementation of a new or modified REMS  
 
See Appendix A:  Important Drug Warning - Model Letter. 
 
B.  Important Prescribing Information Letters 
 
Important Prescribing Information letters (21 CFR 200.5(c)(2)) are used to convey important 
changes to the prescribing information other than those changes that are described in an 
Important Drug Warning letter (section IV.A).  An Important Prescribing Information letter 
ordinarily is used to convey important changes to the INDICATIONS AND USAGE and 
DOSAGE AND ADMINISTRATION sections of the prescribing information.  The types of 
information that are communicated in Important Prescribing Information letters include, but are 
not limited to, the following: 
 
  Change in the INDICATIONS AND USAGE section intended to minimize risk, 
improve effectiveness, or convey a limitation of the indications  
  Change to the dose or dosage regimen intended to minimize risk or improve 
effectiveness 
  Change in the supply of the drug to address a drug shortage issue 
 
A DHCP letter should not be used to merely announce a new indication, even an important one.   
 
If the new information results in the addition of serious risk information to the BOXED 
WARNINGS, CONTRAINDICATIONS, or WARNINGS AND PRECAUTIONS sections of the 
prescribing information, in addition to changes to the INDICATIONS AND USAGE or 
DOSAGE AND ADMINISTRATION sections, the letter should be elevated to an Important 
Drug Warning letter.   
 
See Appendix B:  Important Prescribing Information - Model Letter. 
 
C.  Important Correction of Drug Information Letters 
 
Important Correction of Drug Information letters (21 CFR 200.5(c)(3)) are intended to correct 
false or misleading information or other misinformation in prescription drug promotional 
labeling and advertising that is the subject of a Warning Letter or other Agency action.  This 
  4  Contains Nonbinding Recommendations 
 
guidance provides recommendations for the format and content of such letters (see, in particular, 
section V.A.6).  However, the circumstances in which FDA would seek to have a manufacturer 
disseminate corrective information using a DHCP letter are outside the scope of this guidance.  
 
See Appendix C: Important Correction of Drug Information - Model Letter. 
 
V.  CONTENT AND FORMAT OF DHCP LETTERS 
 
A.  Content Recommendations 
 
In general, FDA believes that a DHCP letter should clearly state the following at or near the 
beginning of the letter to most effectively communicate new information:  
 
  Purpose of the letter (e.g., to inform prescribers about a specific new drug safety issue) 
  Description of the new information 
  Existing information that has changed, if any (e.g., information that is no longer valid in 
light of the new information) 
  Action for a health care provider to take in response to the new information, if any 
 
The letter should be clear and concise and contain sufficient detail to meaningfully inform the 
target audience.  We recommend the letter not exceed two pages (or comparable length of 
electronic content).  The letter should avoid discussion of noncritical information that could 
obscure the more important information and should include the appropriate contact information.  
(See Appendix A for an example of a letter that reflects these recommendations.)  For example, 
if the letter concerns an adverse reaction, it should provide manufacturer and FDA contact 
information for reporting new cases of the reaction.  Ordinarily, it is not sufficient merely to state 
that the labeling has changed and to provide the new labeling language.  New information should 
be summarized, highlighted, and presented using language from the new labeling, as appropriate. 
The recommended content and format for DHCP letters is described below in items 18.  
 
These content recommendations apply to DHCP letters distributed electronically to the extent 
practicable for the type of communication used.  For additional recommendations specific to 
electronic distribution, consult the guidance for industry Using Electronic Means to Distribute 
Certain Product Information.4   
 
1.  Envelope and Letter Heading 
 
Depending on the nature of the information contained in the DHCP letter, one of the following 
statements is required to appear on the envelope (corresponding to the three types of DHCP 
letters described in section IV of this document) (21 CFR 200.5).   
 
  IMPORTANT DRUG WARNING  
 
 
4 We update guidances periodically.  To make sure you have the most recent version of a guidance, check the FDA 
Drugs guidance Web page at http://www.fda.gov/RegulatoryInformation/Guidances/default.htm. 
  5  Contains Nonbinding Recommendations 
 
  IMPORTANT PRESCRIBING INFORMATION  
 
  IMPORTANT CORRECTION OF DRUG INFORMATION 
 
FDA recommends repeating the heading from the envelope on the letter in a similar format 
because mail may be opened and separated from its envelope before reaching the intended 
recipient.  The letter heading may use a smaller font than the envelope heading, if necessary.  For 
a DHCP letter distributed electronically, the letter heading should be the statement that would 
have appeared on the envelope if paper distribution had been used.  The electronic distribution 
guidance referenced in footnote 4 contains recommendations on how to make an electronically 
distributed DHCP letter distinctive in appearance so that it will be promptly recognized and read. 
Additionally, if the letter is distributed by email, FDA recommends using the letter heading as 
the subject line of the email.  FDA also recommends including the letter as the body of the email, 
not as a separate attachment.   
 
2.  Addressees (Target Audience) 
 
A DHCP letter should be directed to all health care providers who are likely to prescribe, 
dispense, or administer the drug, as well as others who need to know the information.  The letter 
should be directed to the full range of health care providers who could prescribe the drug, 
including nurse practitioners and physician assistants who have prescribing authority.  The 
DHCP letter should also be sent to other health care providers who may need to know the 
information even if they do not prescribe the drug.  For example, the emergency departments or 
primary care physicians might not routinely prescribe the drug that is the subject of a DHCP 
letter, but might be providing care for patients with a drug-induced adverse reaction described in 
the letter.  Similarly, a DHCP letter that announces the introduction of a new medication guide 
should be sent to pharmacists who would be required to distribute the medication guide to their 
patients.  
 
3.  Subject Line 
 
A subject line that includes the drug name (proprietary, followed by established or proper) and a 
concise description of the issue that is addressed in the body of the letter (e.g., drug safety 
concern) should immediately follow the letter heading.  The subject line also may include 
characterization of the seriousness of the problem (e.g., serious, life-threatening, or fatal adverse 
reactions) and the population at risk.  Vague terms intended to characterize the incidence of a 
reaction (e.g., rare, infrequent) should generally be avoided.  However, statements regarding a 
well-defined increase in the magnitude of risk or rate of a reaction (e.g., rate of reaction X is 
doubled) and the rate observed in controlled trials or epidemiological studies can be appropriate.  
Consider placing the subject line within a border, text box, or in bold type to further draw 
attention to the information.  See the following examples: 
 
  6  Contains Nonbinding Recommendations 
 
Subject:  Severe, Life-Threatening, and Fatal Cases of Hepatoxicity Reported with 
DRUG NAME 
 
 
Subject:  Limitations on Use of DRUG NAME in Patients with Decreased Renal 
Function Because of Risk of Worsening Renal Function and Increased 
Mortality 
 
 
Subject:   Threefold Increase in Risk of Macular Edema in Elderly Taking DRUG NAME 
 
 
4.  Initial Paragraphs:  Important Drug Warning or Important Prescribing Information 
Letters 
 
In the initial paragraphs of the letter, briefly summarize information essential to a health care 
providers understanding of the nature and management of the problem and actions taken to 
address the issue.  This guidance describes a two-paragraph format, but in some cases a single 
paragraph is adequate to convey the most important information. 
 
Limit the initial paragraphs to the following types of information (to the extent known and 
relevant to the issue that is the subject of the letter): 
 
(a)  First Paragraph:  Concise Description of the Issue 
 
  Product name(s) and brief description of the indications and usage (more 
detail about indications and usage can be included in subsequent paragraphs, 
if warranted) 
 
  Concise description of the issue that gave rise to the new warning or other 
change in the prescribing information, including the nature and severity of 
the issue (e.g., adverse reaction or other potential harm) 
 
  For communicating labeling changes, verbatim language from prescribing 
information may be included if brief (a few sentences).  If the new language 
is lengthy or the change involves more than one section of labeling, 
summarize the new information in the letter and direct the reader to the full 
prescribing information, as appropriate.  
 
  Population(s) at risk (may be a subpopulation of the population for whom 
the drug is indicated) 
 
  Degree of risk, if known.  If there are reliable incidence and/or prevalence 
data from a controlled trial, observational study, or other source, include that 
information.  If the new information is based on spontaneous reports, the 
  7  Contains Nonbinding Recommendations 
 
number of reports may be included if that number is an important factor in 
explaining why FDA is taking regulatory action to revise the prescribing 
information and alert the health care community. 
 
  Whether the risk occurred with indicated or unapproved use of the drug  
 
  Rationale for change in indication, usage or dose 
 
  Availability of a new or modified Medication Guide addressing the issue 
 
(b)  Second Paragraph:  Actions Required to Address the Issue, If Any 
 
  Recommended action, including but not limited to:   
 
  Discontinue use 
o
  Limitations to use (e.g., specific populations, second line therapy) 
o
  Dose reduction 
o
  Patient monitoring for specific clinical findings or laboratory results 
o
  Additional testing required before prescribing 
o
 
  Patient counseling, including but not limited to, advising patients to: 
 
  Contact their health care provider if they experience a specific clinical 
o
sign or symptom 
  Stop the drug immediately if they experience a specific clinical sign or 
o
symptom 
  Consult their health care provider before discontinuing the drug 
o
 
5.  Interior Paragraphs: Important Drug Warning or Important Prescribing 
Information Letters 
 
Use subsequent interior paragraphs, if needed, to provide additional detail that would be helpful 
in understanding the issue, such as: 
 
  Attributes of affected patient populations or subsets 
  Summary of the data or other information that is the basis for a new safety 
warning (e.g., summary information about a controlled clinical trial, 
epidemiologic study, or spontaneous adverse event reporting) 
  Limitations of the data and other information (e.g., what is known and what is not 
known) 
  Mechanism of the adverse reaction 
  Whether the event is common to the drug class 
  Additional research undertaken to better understand an adverse reaction 
  Further discussion of a drugs indication(s) 
 
  8  Contains Nonbinding Recommendations 
 
6.  Correction of Drug Information Letters 
 
For letters intended to correct information in prescription drug advertising or 
promotional labeling, the letter should include: 
   
  Purpose of the letter (to correct false or misleading claims or other 
misinformation)  
  Statement that the information was the subject of a Warning Letter or other 
regulatory action by FDA, if applicable 
  Where and how the incorrect information was conveyed to health care providers 
  The information that was deemed false or misleading and why it was false or 
misleading  
  Corrected information 
  Indication, including limitations to use 
  Risk information 
  Reference to the full prescribing information (which must be enclosed in the 
letter) and to the medication guide or other approved patient information, if any. 
  Statement that the letter is not intended to be a complete description of the 
benefits and risks  
 
In addition, the letter should be free of promotional claims and presentations.   
 
7.  Final Paragraph 
 
The final paragraph should include the following information, to the extent relevant: 
 
  How to report new cases of the adverse reaction or other safety issue described in the 
letter 
  Company contact information for direct inquiries regarding the safety issue 
  FDA contact information 
 
Example: 
 
Health care providers and patients are encouraged to report adverse events in patients 
taking TRADENAME to SPONSOR at 1-800-xxx-xxxx.  You are encouraged to report 
negative side effects of prescription drugs to the FDA.  Visit www.fda.gov/medwatch, or 
call 1-800-FDA-1088. 
 
You also may contact our medical information department at 1-800--xxx-xxxx if you 
have any questions about the information contained in this letter or the safe and effective 
use of TRADENAME. 
 
Also include reference to the full prescribing information (which must be enclosed in the letter) 
and to the medication guide or other approved patient information, if any. 
 
  9  Contains Nonbinding Recommendations 
 
8.   Types of Information That Should Not Be in a DHCP Letter 
 
Additional detail that could obscure more important information or divert attention from more 
important information should be omitted.  Examples of such information include, but are not 
limited to: 
   
  Market information about the drug, including numbers of prescriptions, patient 
exposures, approvals, and pending approvals 
  Extensive details about the design of a clinical study 
  Information about a safety review panel  
  Plans to further investigate the problem, if not specifically related to safety 
  Promotional language or claims 
 
B.  Format Recommendations 
 
Format the letter in a way that will help make the information in the letter easily accessible to the 
reader.  We recommend using typographic and formatting techniques to maximize readability, 
including: 
 
  Two-page limit 
  Informative paragraph headings 
  Vertical lists with bullets or numbering, where appropriate 
  Text emphasis techniques to draw attention to major points (e.g., bold font, larger 
font, italics) 
  Minimum 12-point font 
  Easily readable font based on the type of media used (e.g., serif or sans serif) 
  Use of upper and lowercase letters (i.e., avoid all caps) 
  Adequate spacing and leading (i.e., letters should not touch within lines; lines of 
text should not touch one another) 
  Use of white space to delineate paragraphs and organize text5  
 
These format recommendations also apply to DHCP letters distributed electronically to the 
extent practicable for the type of communication used (see footnote 4). 
 
VI.  ASSESSMENT OF THE DHCP LETTER IMPACT 
 
Manufacturers should conduct an evaluation, for their own use, of the extent to which the target 
audience received the DHCP letter and is aware of the information that was communicated in the 
letter.   
 
If the DHCP letter is part of a REMS, there must be an evaluation plan in place, as specified in 
the REMS.  Additional information on REMS evaluations may be found in the draft guidance for 
 
5 See, for example, Chapparro B, Baker JR, Shaikh AD, Hull S, and Brady L, 2004, Reading Online Text:  A 
Comparison of Four White Space Layouts, Usability News, 6(2).  Available at 
http://psychology.wichita.edu/surl/usabilitynews/62/whitespace.htm. 
  10  Contains Nonbinding Recommendations 
 
industry Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), 
REMS Assessments, and Proposed REMS Modifications.6   
 
VII.  PAPERWORK REDUCTION ACT OF 1995 
 
This guidance contains information collection provisions that are subject to review by the Office 
of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
(44 U.S.C. 3501-3520).  The time required to complete this information collection is estimated to 
average 100 hours per response, including the time to review instructions, search existing data 
sources, gather the data needed, and complete and review the information collection.  Send 
comments regarding this burden estimate or suggestions for reducing this burden to:   
 
Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Avenue, WO Bldg. 51, Silver Spring, MD  20993-0002 
 
 
 
An Agency may not conduct or sponsor, and a person is not required to respond to, a collection 
of information unless it displays a currently valid OMB control number.  The OMB control 
number for this information collection is 0910-0754.  The current expiration date is available at 
https://www.reginfo.gov (search ICR and enter OMB control number 0910-0754). 
 
 
 
 
6 When final, this guidance will represent the FDAs current thinking on this topic.   
  11  Contains Nonbinding Recommendations 
 
 
APPENDIX A 
 
Month Year 
 
IMPORTANT DRUG WARNING - MODEL LETTER 
 
 
  Subject:  Serious Risks with Use of Tradename (established name) Tablets: 
    Central Nervous System Posttransplant 
  Lymphoproliferative Disorder (PTLD), and 
    Progressive Multifocal Leukoencephalopathy (PML) 
 
 
 
Dear Health Care Provider: 
 
The purpose of this letter is to inform you of important safety information for Tradename, a 
selective co-stimulation blocker approved for prophylaxis of organ rejection in adult patients 
receiving liver transplants. 
 
Serious Risks With Use of Tradename 
 
Risk of Central Nervous System Posttransplant Lymphoproliferative Disorder (PTLD) and 
Progressive Multifocal Leukoencephalopathy (PML) 
  Patients treated with Tradename are at an increased risk for developing PTLD, specifically 
involving the central nervous system (CNS), which can be fatal. 
  Risk factors for PTLD include cytomegalovirus (CMV) infection and T cell depleting 
therapy. 
  In clinical trials with Tradename, three cases of PML were reported in patients receiving 
Tradename at doses higher than the recommended regimen. 
 
Contraindications (use only if relates to new drug warning) 
Tradename is contraindicated in transplant recipients with CMV infection. 
 
Prescriber Action 
 
Counsel patients about the risks and benefits of Tradename, including: 
  The potential risks for PTLD and PML 
  The need for CMV prophylaxis for at least 6 months after transplantation 
 
Tell your patients to contact their doctor immediately to report any changes in memory, speech, 
behavior, or vision. 
  12  Contains Nonbinding Recommendations 
 
 
Reporting Adverse Events 
 
Health care providers and patients are encouraged to report adverse events in patients taking 
TRADENAME to SPONSOR at 1-800-xxx-xxxx.  You are encouraged to report negative side 
effects of prescription drugs to the FDA.  Visit www.fda.gov/medwatch, or call 1-800-FDA-
1088. 
 
You may also contact our medical information department at 1-800-xxx-xxxx if you have any 
questions about the information contained in this letter or the safe and effective use of 
Tradename. 
 
This letter is not intended as a complete description of the benefits and risks related to the use of 
Tradename.  Please refer to the enclosed full prescribing information (and medication guide, if 
there is a medication guide for this product, or any other approved patient information). 
 
 
Sincerely, 
 
 
 
Company Representative 
 
 
 
Enclosure(s):  Tradename Full Prescribing Information 
 
 
 
 
  13  Contains Nonbinding Recommendations 
 
APPENDIX B 
 
Month Year 
 
 
IMPORTANT PRESCRIBING INFORMATION - MODEL LETTER 
 
 
Subject:     Introducing New Strength for Tradename (established name) for Oral 
Suspension:  Changing the Concentration from 12 mg/mL to 6 mg/mL and 
Dispenser From mgs to mLs 
 
 
Dear Health Care Provider: 
 
The purpose of this letter is to introduce a new strength of Tradename for Oral Suspension 
6 mg/mL.  We have changed the concentration from 12 mg/mL to 6 mg/mL and the dispenser 
from mgs to mLs to help reduce the potential for prescribing and dosing confusion.  The 
12 mg/mL concentration is no longer being manufactured.  Tradename is indicated in patients 
1 year and older for treatment of uncomplicated influenza.  
 
Dosing and Administration 
 
The dosing for Tradename for mL (Oral Suspension) is based on the patients weight.  A 10 mL 
oral dosing dispenser is provided with the oral suspension.  Patients with a weight of 15 kg 
(33 lbs) or less should receive 5 mL of the oral suspension for each dose.  Patients weighing 
16 kg thru 23 kg (34 lbs thru 51 lbs) should receive 7.5 mL per dose.  Patients weighing 24 kg 
thru 40 kg (52 lbs thru 88 lbs) should receive 10 mL per dose; and patients weighing 41 kg 
(89 lbs) or more should receive 12.5 mL for each dose.  (This requires administering a 10 mL 
dose, followed by another 2.5 mL dose.)  Frequency for treatment is twice daily for 5 days.  
 
Prescriber Action (use only if relates to new prescribing information) 
 
Counsel patients about the risks and benefits of Tradename, including: 
  The new dosing requirements to ensure appropriate dosing. 
  The potential risks for X . . . .   
  Patients should stop using the drug immediately if they experience zzz side effect. 
  Patients should contact their doctor immediately if they experience abcd side effect. 
 
Reporting Adverse Events 
 
Heath care providers and patients are encouraged to report adverse events in patients taking 
TRADENAME to SPONSOR at 1-800-xxx-xxxx.  You are encouraged to report negative side 
effects of prescription drugs to the FDA.  Visit www.fda.gov/medwatch, or call 1-800-FDA-
1088. 
 
  14  Contains Nonbinding Recommendations 
 
You may also contact our medical information department at 1-800-xxx-xxxx if you have any 
questions about the information contained in this letter or the safe and effective use of 
Tradename. 
 
This letter is not intended as a complete description of the benefits and risks related to the use of 
Tradename.  Please refer to the enclosed full prescribing information (and medication guide, if 
there is a medication guide for the product, or any other approved patient information).  
 
For additional information, please call Sponsor at 1-800-xxx-xxxx or visit www.tradename.com. 
 
 
Sincerely, 
 
 
Company Representative 
 
 
Enclosure(s):  Tradename Full Prescribing Information  
 
  15  Contains Nonbinding Recommendations 
 
APPENDIX C 
 
Month Year 
 
CORRECTION OF DRUG INFORMATION - MODEL LETTER 
 
 
 
Subject:   Correction of Information for Tradename (established name) Tablets in 
 
response to FDA Warning Letter  
 
 
 
 
Dear Health Care Provider: 
 
You may have seen a Sales Aid for Tradename (established name) Tablets distributed by 
SPONSOR sales representatives.  The U.S. Food and Drug Administration (FDA) issued a 
Warning Letter to SPONSOR because it determined that the Sales Aid failed to include 
important risk information regarding Tradename.  This letter is being sent to you at the request of 
the U.S. Food and Drug Administrations (FDA) Office of Prescription Drug Promotion (OPDP).   
 
Important Risk Information Omitted from the Tradename Sales Aid Outlined in the FDA 
Warning Letter 
 
Risk of Central Nervous System Posttransplant Lymphoproliferative Disorder (PTLD) and 
Progressive Multifocal Leukoencephalopathy (PML) 
  Patients treated with Tradename are at an increased risk for developing PTLD, specifically 
involving the central nervous system (CNS), which can be fatal. 
  Risk factors for PTLD include cytomegalovirus (CMV) infection and T cell depleting 
therapy. 
  In clinical trials with Tradename, three cases of PML were reported in patients receiving 
Tradename at doses higher than the recommended regimen. 
 
Indication for Tradename 
 
Tradename is indicated for the prophylaxis of organ rejection in adult patients receiving liver 
transplants. 
 
This letter is not intended as a complete description of the benefits and risks related to the use of 
Tradename.  Please refer to the enclosed full prescribing information (and medication guide, if 
there is a Medication Guide for the product, or any other approved patient information).  
 
Reporting Adverse Events 
 
Heath care providers and patients are encouraged to report adverse events in patients taking 
TRADENAME to SPONSOR at 1-800- xxx-xxxx.  You are encouraged to report negative side 
  16  Contains Nonbinding Recommendations 
 
effects of prescription drugs to the FDA.  Visit www.fda.gov/medwatch, or call 1-800-FDA-
1088. 
 
You may also contact our medical information department at 1-800-xxx-xxxx if you have any 
questions about the information contained in this letter or the safe and effective use of 
Tradename. 
 
For additional information, please call Sponsor at 1-800-xxx-xxxx or visit www.tradename.com. 
 
 
Sincerely, 
 
 
 
Company Representative 
 
 
 
Enclosure(s):  Tradename Full Prescribing Information  
 
  17