Dosage and Administration 
Section of Labeling for 
Human Prescription Drug 
and Biological Products  
Content and Format 
Guidance for Industry  
 
 
DRAFT GUIDANCE 
 
  This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 60 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance.  Submit electronic comments to https://www.regulations.gov.  Submit written 
comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD  20852.  All comments should be identified with the 
docket number listed in the notice of availability that publishes in the Federal Register. 
 
For questions regarding this draft document, contact (CDER) Eric Brodsky at (301) 796-0855, or 
(CBER) the Office of Communication, Outreach, and Development at 800-835-4709 or 240-402-
8010. 
 
 
 
 
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 2023 
Labeling 
Revision 1 
46227790dft.docx 
10/17/22   
Dosage and Administration 
Section of Labeling for 
Human Prescription Drug 
and Biological Products  
Content and Format 
Guidance for Industry  
 
Additional copies are available from: 
 
Office of Communications, Division of Drug Information 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD  20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs 
 
and/or 
 
Office of Communication, Outreach, and Development  
Center for Biologics Evaluation and Research 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD  20993-0002 
Phone: 800-835-4709 or 240-402-8010 
Email: ocod@fda.hhs.gov 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-
guidances 
 
 
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 2023 
Labeling 
Revision 1 
   
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  GENERAL PRINCIPLES................................................................................................ 2 
III.  ORGANIZATION AND FORMAT ................................................................................ 4 
A.  Subsections ..................................................................................................................................... 4 
B.  Tables and Figures ......................................................................................................................... 6 
IV.  CONTENT ......................................................................................................................... 6 
A.  Critical Information for the Safe and Effective Use of the Drug ............................................... 7 
B.  Fundamental Dosage- and Administration-Related Information ............................................. 9 
1. Recommended Starting or Loading Dose or Dosage ..................................................................... 10 
2. Recommended Titration Schedule .................................................................................................. 10 
3. Maximum Recommended Dosage .................................................................................................. 11 
4. Maximum Recommended Duration ................................................................................................ 11 
5. Recommended Dosage in Pediatric Patients ................................................................................. 12 
6. Recommended Dosage in Geriatric Patients ................................................................................. 12 
7. Recommended Dosage for Fixed-Combination Drug Products and Co-Packaged Products ....... 13 
8. Administration Instructions Included With the Recommended Dosage ......................................... 14 
9. Recommended Monitoring for Effectiveness .................................................................................. 14 
C.  Other Therapy Used Before, During, or After Drug Treatment or Administration ............. 15 
1. Other Therapy Used Before Drug Administration ......................................................................... 15 
2. Other Therapy Used During or After Drug Treatment or Administration .................................... 16 
D.  Dosage Modifications ................................................................................................................... 16 
1. Dosage Modifications Intended to Reduce the Risk of Adverse Reactions .................................... 16 
2. Dosage Modifications for Drug Interactions ................................................................................. 17 
E.  Dosage in Patients With Renal Impairment .............................................................................. 18 
F.  Dosage in Patients With Hepatic Impairment ........................................................................... 21 
G.  Dosage in Other Specific Populations ........................................................................................ 21 
H.  Information About Switching and Substitution ........................................................................ 22 
1. Switching to the Subject Drug ........................................................................................................ 22 
2. Cautionary Statements Relating to Substitution ............................................................................ 22 
I.  Recommendations Regarding Missed Dose(s) ........................................................................... 23 
J.  Recommendations in Event of Vomiting After Oral Drug Administration ........................... 23 
K.  Recommendations for Drug Discontinuation or Dosage Reduction When There Are Risks of 
Withdrawal ................................................................................................................................... 23 
L.  Additional Preparation and Administration Instructions........................................................ 23 
1. Preparation and Administration Instructions for Parenteral Products ......................................... 25 
2. Administration Instructions for Certain Dosage Forms ................................................................ 26 
3. Preparation of a Product Stored in the Refrigerator or Freezer ................................................... 27 
4. Preparation and Storage of Pharmacy Bulk Packages ................................................................. 28 
5. Preparation/Administration of Solid Oral Dosage Forms With Qualified Liquids or Soft Foods 28 
i   
6. Preparation and Administration of Oral Dosage Forms Via Enteral Tubes ................................. 29 
7. Instructions to Avoid Harm Related to Drug Handling and Administration ................................. 29 
8. Information on Drug Incompatibilities If the Drug Is Mixed In Vitro With Other Drugs ............. 30 
9. Radiation Dosimetry ...................................................................................................................... 30 
10.  Liposome Drug Products ........................................................................................................... 30 
M.  Storage Instructions for the Reconstituted or Diluted Product ............................................... 30 
V.  ADDITIONAL RECOMMENDATIONS ..................................................................... 31 
A.  Abbreviations and Symbols ........................................................................................................ 31 
B.  Metric System ............................................................................................................................... 32 
C.  USP Descriptor ............................................................................................................................. 32 
ii  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1  Dosage and Administration Section of Labeling for Human 
2  Prescription Drug and Biological Products  Content and Format 
3  Guidance for Industry1 
4   
5   
6   
7  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
8  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
9  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
10  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
11  for this guidance as listed on the title page. 
12   
13   
14   
15  I.  INTRODUCTION  
16   
17  This guidance is intended to assist applicants in developing the DOSAGE AND 
18  ADMINISTRATION section of labeling as described in 21 CFR 201.57(c)(3), a regulation 
19  governing the content and format of this section of human prescription drug and biological 
20  product labeling,2 to ensure that this section contains the dosage- and administration-related 
21  information needed for safe and effective use of a drug.3,4  Applicants should follow the 
22  recommendations in this guidance when developing the DOSAGE AND ADMINISTRATION 
23  section for a new drug submitted to FDA under a new drug application under section 505(b) of 
 
1 This guidance has been prepared by the Labeling Policy Team, in collaboration with other staff in the Office of 
New Drugs; other offices in the Center for Drug Evaluation and Research (including the Office of Clinical 
Pharmacology, Office of Generic Drugs, Office of Medical Policy, Office of Pharmaceutical Quality, Office of 
Regulatory Policy, Office of Surveillance and Epidemiology); and the Center for Biologics Evaluation and Research 
at the Food and Drug Administration. 
 
2 For the purposes of this guidance, references to drugs, drug products, and drug and biological products include 
drugs approved under section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355) and 
biological products licensed under section 351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262) that are 
regulated as drugs. 
 
3 The standard for licensure of a biological product as potent under section 351(a) of the PHS Act has long been 
interpreted to include effectiveness (see 21 CFR 600.3(s)).  In this guidance, we use the terms safety and 
effectiveness and safety, purity, and potency synonymously in the discussions pertaining to biological products.  See 
also the guidance for industry Providing Clinical Evidence of Effectiveness for Human Drug and Biological 
Products (May 1998) and the draft guidance for industry Demonstrating Substantial Evidence of Effectiveness for 
Human Drug and Biological Products (December 2019).  When final, this guidance will represent the FDAs 
current thinking on this topic.  For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
 
4 This is one of many guidance documents addressing labeling for human prescription drugs.  For additional human 
prescription drug labeling guidance documents, see the FDAs Labeling Resources for Human Prescription Drugs 
website (available at https://www.fda.gov/drugs/laws-acts-and-rules/fdas-labeling-resources-human-prescription-
drugs). 
 
  1  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
24  the FD&C Act or a biologics license application under section 351(a) of the PHS Act, and when 
25  revising existing information in the labeling for a currently approved drug in a supplement to 
26  such applications.5  This guidance provides examples (denoted with a sawtooth line in the left 
27  margin) of required and recommended information in the DOSAGE AND ADMINISTRATION 
28  section.6  
29   
30  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
31  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
32  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
33  the word should in Agency guidances means that something is suggested or recommended, but 
34  not required.  
35   
36   
37  II.  GENERAL PRINCIPLES 
38   
39  Information in the DOSAGE AND ADMINISTRATION section should be presented in a clear, 
40  concise manner, using active voice and command language whenever possible.  Because the 
41  Prescribing Information is written for health care practitioners, information in this section should 
42  be presented in a manner that is pertinent and understandable to health care practitioners, which 
43  can help reduce medication errors.7 
44   
45  Dosing regimens must not be implied or suggested in other sections of the labeling if not 
46  included in this section.8  This section must be updated when new information becomes available 
47  that causes the labeling to be inaccurate, false, or misleading.9  Applicants should review this 
48  section at least annually10 to ensure that this section contains accurate, clear, and up-to-date 
49  information.  Information that would ordinarily be required in this section may be omitted if the 
50  information is clearly inapplicable.11 
 
5 See generally, 21 CFR parts 314 and 601. 
 
6 In the notice announcing the availability of this draft guidance, FDA also withdrew the guidance for industry 
Dosage and Administration Section of Labeling for Human Prescription Drug and Biological Products  Content 
and Format (March 2010), which formerly provided FDAs thinking relating to certain information in the DOSAGE 
AND ADMINISTRATION section.  
 
7 Complicated or detailed patient-use instructions regarding preparation, administration, storage, and/or disposal of 
prescription drugs that are written for patients or caregivers can typically be found in FDA-approved patient labeling 
(e.g., Instructions for Use).  See the guidance for industry Instructions for Use  Patient Labeling for Human 
Prescription Drug and Biological Products  Content and Format (July 2022). 
 
8 21 CFR 201.57(c)(3)(ii) and 21 CFR 201.57(c)(15)(i). 
 
9 21 CFR 201.56(a)(2). 
 
10 See section VII.B. (Changes to the Regulations for Applications Not Covered by the Final Rule) in the guidance 
for industry Labeling for Human Prescription Drug and Biological Products  Implementing the PLR Content and 
Format Requirements (February 2013).  
 
11 See 21 CFR 201.56(d)(4). 
 
  2  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
51   
52  When developing the DOSAGE AND ADMINISTRATION section, consider if information is 
53  more appropriate for other sections or subsections of labeling (e.g., package type information 
54  should generally be included in the DOSAGE FORMS AND STRENGTHS and HOW 
55  SUPPLIED/STORAGE AND HANDLING sections rather than the DOSAGE AND 
56  ADMINISTRATION section).   
57   
58  Cross-references to detailed discussions in other sections of labeling that provide the basis for 
59  recommendations in the DOSAGE AND ADMINISTRATION section should be included in this 
60  section, as appropriate, such as including a cross-reference to the Pharmacokinetics subsection of 
61  the CLINICAL PHARMACOLOGY section that provides the rationale for when a drug should 
62  be administered with food.12   
63   
64  When developing the DOSAGE AND ADMINISTRATION section, applicants should use the 
65  term dose to refer to a specific amount of drug taken at one time, and the term dosage to refer to 
66  a specific amount of drug administered at a specific frequency (and over a certain duration, if 
67  applicable).  The appropriate term (dosage versus dose) should be used throughout the labeling 
68  depending on the information being discussed.   
69   
70  Except where noted in this guidance, information that is not directly related to dosage, 
71  preparation, or administration of the drug or storage of the prepared product should ordinarily 
72  not be included in the DOSAGE AND ADMINISTRATION section to avoid distracting from or 
73  competing with the required and recommended information in this section.  Such information 
74  may be appropriate for inclusion in other sections of labeling.  For example, FDA generally 
75  recommends avoiding including the following information in the DOSAGE AND 
76  ADMINISTRATION section:  
77   
78    Contraindications or statements when use is inadvisable (e.g., avoid use, not 
79  recommended) in a specific population or with concomitant use of another drug.13   
80   
81    Efficacy data (e.g., After 4 weeks of therapy, 40% and 10% of patients treated with 
82  DRUG-X and placebo achieved a response, respectively.)14  
83   
84  Information that is not specific to the drug and is considered general medical knowledge (e.g., 
85  information such as use the optimal dosage or statements such as individual patients will 
86  experience a variable time to onset and degree of symptom improvement) should generally not 
 
12 See section IV.B. (Using Cross-References) in the guidance for industry Labeling for Human Prescription Drug 
and Biological Products  Implementing the PLR Content and Format Requirements. 
 
13 See sections IV.D.2., E., and F. of this guidance for exceptions to this recommendation. 
 
14 Information on time to achieve a clinically significant effect (e.g., a time to event endpoint), if appropriate, should 
generally be included in the CLINICAL STUDIES section instead of the DOSAGE AND ADMINISTRATION 
section.  See also the appendix in the guidance for industry Clinical Studies Section of Labeling for Human 
Prescription Drug and Biological Products  Content and Format (January 2006).   
 
  3  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
87  be included in this section to avoid distracting from or competing with the required and 
88  recommended information in this section.   
89   
90   
91  III.  ORGANIZATION AND FORMAT 
92   
93  Information in the DOSAGE AND ADMINISTRATION section should be organized and 
94  presented in a manner that promotes comprehension and readability.  Because the amount and 
95  type of information in this section vary considerably across drugs, a range of different 
96  organizational schemes may adequately achieve comprehension and readability. 
97   
98  The sequence of dosage- and administration-related information in this section should be based 
99  on its relative clinical importance.  The most clinically relevant dosage- and administration-
100  related information should generally appear first (e.g., the recommended dosage for each 
101  indication and subpopulation, the route(s) of administration, instructions on how and when to 
102  administer an orally administered drug relative to the ingestion of food or food substances).15  
103  Other types of dosage- and administration-related information (e.g., dosage modifications for 
104  drug interactions, instructions on how to reconstitute the supplied lyophilized powder, 
105  instructions on how to administer a solid oral dosage form with qualified liquids or soft foods) 
106  should generally appear later in the section.   
107   
108  A.  Subsections  
109   
110  Distribution of content into subsections or addition of headings within subsections16 in the 
111  DOSAGE AND ADMINISTRATION section may be used to enhance the organization, 
112  presentation, and accessibility of information.17  If subsections are created, FDA recommends 
113  the following: 
114   
115    Using subsection headings that accurately reflect the content.   
116   
117    Presenting the recommended dosage information in a single subsection if the 
118  recommended dosage for a drug is the same across multiple approved indications or 
119  subpopulations.  
120   
121    Placing all information under subsections instead of inserting information between the 
122  section heading and first subsection heading (i.e., capture information under numbered 
123  subsections instead of between the section 2 heading and subsection 2.1) because floating 
 
15 See section IV.B. in this guidance. 
 
16 Headings may also be added under the DOSAGE AND ADMINISTRATION section if there are no subsections. 
 
17 See 21 CFR 201.56(d)(2).  Because subsection headings are required to appear in the Full Prescribing 
Information: Contents (Table of Contents) (see 21 CFR 201.57(b)), the inclusion of subsections in the DOSAGE 
AND ADMINISTRATION section may assist health care practitioners with locating specific dosage- and 
administration-related information.   
 
  4  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
124  content will not be associated with a specific subsection heading in Full Prescribing 
125  Information: Contents18 and may therefore be less accessible.19 
126   
127    Creating separate subsections for lengthy or complex information (e.g., 2.x Preparation 
128  Instructions and 2.x Administration Instructions).  However, a single subsection 
129  should be considered when such information is straightforward (e.g., 2.x Preparation 
130  and Administration Instructions). 
131   
132  If separate subsections are used for the recommended dosage for distinct indications in the 
133  DOSAGE AND ADMINISTRATION section, FDA recommends distinguishing these 
134  subsection headings from subsection headings in the INDICATIONS AND USAGE section20 so 
135  health care practitioners can more easily locate information about the approved indications and 
136  the recommended dosage.  For example, if the INDICATIONS AND USAGE section includes 
137  the headings 1.1 Disease-A and 1.2 Disease-B, instead of using the same subheadings (i.e., 2.1 
138  Disease-A and 2.2 Disease-B), use 2.1 Recommended Dosage for Disease-A and 2.2 
139  Recommended Dosage for Disease-B in the DOSAGE AND ADMINISTRATION section. 
140   
141  In uncommon circumstances, if a drug has very complicated dosage- and administration-related 
142  information, then this section may include a subsection that provides a summary of these 
143  complicated recommendations and/or instructions (e.g., 2.x Dosage and Administration 
144  Overview, 2.x Dosage Overview).  This subsection should generally appear first with a cross-
145  reference to details that appear in the other subsections in this section. 
146   
 
18 See 21 CFR 201.57(b). 
 
19 If labeling has floating content between the section 2 heading and subsection 2.1, FDA recommends that 
applicants move the floating content to the appropriate subsection(s) in the DOSAGE AND ADMINISTRATION 
section.  
 
20 Subsection headings are not required under the INDICATIONS AND USAGE section; thus, the indications for 
Disease-A and Disease-B may be listed directly under the INDICATIONS AND USAGE section heading. 
 
  5  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
147  B.  Tables and Figures  
148   
149  For complex dosage, preparation and administration instructions, or dosage modifications 
150  intended to reduce the risk of adverse reactions,21,22 FDA recommends using tables,23 figures, 
151  bulleted lists, or algorithms in the DOSAGE AND ADMINISTRATION section.  Table and 
152  figure titles should reflect the content (e.g., if this section includes two or more tables with 
153  dosage- and administration-related information about different subpopulations, each table title 
154  should include the subpopulation) and should appear in bolded, title case.  The text preceding the 
155  table or figure should briefly mention or identify the content in the table or figure (e.g., See 
156  Table 1 for the recommended dosage in pediatric patients aged X years and older.).    
157   
158   
159  IV.  CONTENT  
160   
161  Information that must appear in the DOSAGE AND ADMINISTRATION section includes, but 
162  is not limited to, the drugs recommended dose24 and, as appropriate: 
163   
164    The dosage range25 
165   
166    An upper limit beyond which safety and effectiveness have not been established, or 
167  beyond which increasing the dose does not result in increasing effectiveness26 
168   
169    Dosages for each indication and subpopulation27 
170   
 
21 For the purposes of prescription drug labeling, an adverse reaction is an undesirable effect, reasonably associated 
with use of a drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its 
occurrence.  This definition does not include all adverse events observed during use of a drug, only those adverse 
events for which there is some basis to believe there is a causal relationship between the drug and the occurrence of 
the adverse event.  See 21 CFR 201.57(c)(7).   
 
22 See section IV.D.1. of this guidance. 
 
23 Integrating a human factors engineering process in the development of tables that include a large amount of 
complex dosing information is recommended to ensure their design supports the users needs and minimizes 
medication errors. 
 
24 21 CFR 201.57(c)(3)(i).  We recommend that the term usual dose be avoided in drug labeling subject to the 
content and format requirements under 21 CFR 201.56(d) and 201.57.  The term usual dose does not appear in 21 
CFR 201.57, which is the subject of this guidance, and could be interpreted to refer to the most prescribed dose, 
which may be inconsistent with the recommended dose. 
 
25 21 CFR 201.57(c)(3)(i)(A). 
 
26 21 CFR 201.57(c)(3)(i)(B). 
 
27 21 CFR 201.57(c)(3)(i)(C). 
 
  6  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
171    The intervals recommended between doses28 
172   
173    The optimal method of titrating dosage29 
174   
175    The usual duration of treatment when treatment duration should be limited30 
176   
177    Dosing recommendations based on clinical pharmacologic data31 
178   
179    Specific direction on administration of the dosage form32 (e.g., route(s) of 
180  administration)33   
181   
182  The titles of headings in this section of the guidance are being used to organize information in 
183  the guidance and do not necessarily represent FDA recommendations for specific subsection 
184  headings to be used in the DOSAGE AND ADMINISTRATION section of labeling.  
185   
186  The DOSAGE AND ADMINISTRATION section generally presents the following categories of 
187  information, if applicable to the drug.  For many drugs, not all categories described below will be 
188  applicable.   
189   
190  A.  Critical Information for the Safe and Effective Use of the Drug 
191    
192  When certain dosage- and administration-related information is particularly critical to the safe 
193  and effective use of the drug (e.g., lack of knowledge of the information or nonadherence to a 
194  recommendation could have serious consequences for patients), this information should appear 
195  as the first information presented within the DOSAGE AND ADMINISTRATION section.  A 
196  cross-reference should be included to other subsection(s) in this section or other sections of 
197  labeling that contain additional details (e.g., WARNINGS AND PRECAUTIONS).34  Examples 
198  include but are not limited to the following situations:  
199   
 
28 21 CFR 201.57(c)(3)(i)(D). 
 
29 21 CFR 201.57(c)(3)(i)(E). 
 
30 21 CFR 201.57(c)(3)(i)(F). 
 
31 21 CFR 201.57(c)(3)(i)(G). 
 
32 21 CFR 201.57(c)(3)(iv). 
 
33 See 21 CFR 201.100(d)(1). 
 
34 Detailed descriptions of the clinically significant adverse reactions or risks, or the steps to take to prevent, 
mitigate, monitor for, or manage the adverse reactions or risks that are not related to dosage or administration 
modifications should be described in the WARNINGS AND PRECAUTIONS section instead of the DOSAGE 
AND ADMINISTRATION section. See section II. (WARNINGS AND PRECAUTIONS SECTION) in the 
guidance for industry Warnings and Precautions, Contraindications, and Boxed Warning Sections of Labeling for 
Human Prescription Drug and Biological Products - Content and Format (October 2011). 
 
  7  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
200    Medication errors35 (e.g., attributable to an inappropriate route of administration) have 
201  occurred and resulted in serious adverse reactions.  
202   
203    The dosage form (e.g., injection) needs to be diluted before administration because 
204  administration of undiluted drug may result in toxicity. 
205   
206    Inappropriate substitution of one drug for another drug (e.g., substituting drugoxide 
207  liposome injection for drugoxide injection)36 may lead to clinically significant adverse 
208  reaction(s) or loss of effectiveness.37 
209   
210    Infusion rates that exceed the maximum recommended infusion rate have resulted in 
211  clinically significant adverse reactions (e.g., hypotension).   
212   
213    Contact with the product has serious consequences for the patient or the health care 
214  practitioner (e.g., radiation safety for radiopharmaceuticals or safe handling of a container 
215  with dry natural rubber or natural rubber latex).38   
216   
217    FDA has determined that a drug must be administered in a specific health care setting 
218  (e.g., hospital) or by a specific user (e.g., health care practitioner only).39  
219   
220    Evaluations, procedures, or tests (e.g., pregnancy testing in females of reproductive 
221  potential for a drug that has embryo-fetal toxicity) are required40 or necessary (e.g., 
 
35 For the purposes of this guidance, a medication error is any preventable event that may cause or lead to 
inappropriate medication use or patient harm while the medication is in the control of the health care practitioner or 
patient (see also National Coordinating Council for Medication Error Reporting and Prevention, About Medication 
Errors | NCC MERP available at https://www.nccmerp.org/about-medication-errors). 
 
36 The DOSAGE AND ADMINISTRATION section should include a statement recommending against substituting 
the liposome drug product for the nonliposome product or another liposome drug product that contains the same 
active ingredient unless FDA has determined that the products are therapeutically equivalent.  See the guidance for 
industry Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and 
Bioavailability; and Labeling Documentation (April 2018). 
 
37 See section IV.H.2. of this guidance. 
 
38 See the guidance for industry and FDA staff Recommendations for Labeling Medical Products to Inform Users 
that the Product or Product Container is not Made with Natural Rubber Latex (December 2014). 
 
39 A labeling provision such as this may be based on a risk evaluation and mitigation strategy that FDA approved 
with elements to assure safe use (ETASU).  In this case, the drugs ETASU may require that (1) the drug be 
dispensed to patients only in certain health care settings, such as hospitals; (2) health care practitioners who 
prescribe the drug have particular training or experience, or are specially certified; (3) pharmacies, practitioners, or 
health care settings that dispense the drug are specially certified; (4) the drug be dispensed to patients with evidence 
or other documentation of safe-use conditions, such as laboratory test results; (5) the patient using the drug be 
subject to certain monitoring; or (6) each patient using the drug be enrolled in a registry.  See Section 505-l(f)(3) of 
the FD&C Act. 
 
40 Ibid.   
 
  8  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
222  evaluating for active tuberculosis and testing for latent tuberculosis) before drug 
223  initiation.  For example: 
224   
225  2.x Recommended Evaluation and Testing Before Initiating DRUG-X 
226  Before initiating DRUG-X, evaluate for active tuberculosis and test for latent 
227  tuberculosis [see Warnings and Precautions (5.1)].   
228   
229  B.  Fundamental Dosage- and Administration-Related Information 
230   
231  Unless there is critical information for the safe and effective use of the drug (as described in 
232  section IV.A. of this guidance), FDA generally recommends that the following information 
233  appear first within the DOSAGE AND ADMINISTRATION section, because this information 
234  describes the fundamental dosage- and administration-related information:41  
235   
236    Recommended dosage information: 
237   
238    This section should express the recommended dosage in terms of the drugs 

239  recommended dose and, as appropriate, the recommended intervals between doses 
240  (i.e., dosing frequency) and duration, if applicable, for each indication.  FDA 
241  generally recommends using the term recommended dosage, as appropriate, in this 
242  section of labeling.42  
243   
244    If appropriate for the drug, the dosage range must be included in this section43 and 

245  should be included with the other recommended dosage information.  
246   
247    If applicable, this section should include the recommended starting or loading dose or 

248  dosage; the recommended titration schedule; the maximum recommended dosage; 
249  and the maximum recommended duration.44 
250   
251    For weight-based or body surface area-based dosing based on ideal or adjusted body 

252  weight, this section should identify the method for calculating the dose.   
253   
254    If applicable, this section should include therapeutic drug monitoring information.45 

 
41 If there is critical information for the safe and effective use of the drug (as described in section IV.A. of this 
guidance), then the recommended dosage and administration information described in this section of the guidance 
(section IV.B.) will generally appear immediately after the critical information for the safe and effective use of the 
drug in the DOSAGE AND ADMINISTRATION section. 
 
42 FDA recommends that the term usual dosage be avoided in drug labeling subject to the content and format 
requirements under 21 CFR 201.56(d) and 201.57.  The term usual dosage could be interpreted to refer to the most 
prescribed dosage, which may be inconsistent with the recommended dosage. 
 
43 21 CFR 201.57(c)(3)(i)(A). 
 
44 See sections IV.B.1., IV.B.2., IV.B.3., and IV.B.4. in this guidance, respectively. 
 
45 See section IV.B.9. in this guidance. 
 
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255   
256    If applicable, this section should include the formula or formulas for calculating the 

257  recommended dosage.  
258   
259    Administration instructions included with the recommended dosage (e.g., route(s) of 
260  administration)46   
261   
262  If there are important considerations concerning compliance with the dosage regimen47 (e.g., 
263  patient adherence to the recommended dosage), this information must be included in this section 
264  and because of its importance, should appear with the elements cited above, appearing close to 
265  the beginning of this section.  For example, if adherence to a precise dosage is particularly 
266  important for the safe and effective use of the drug (e.g., if doses should be given 8 hours apart 
267  instead of three times a day), this section should include such information and cross-reference 
268  other sections of the labeling that describe the data supporting these specific recommendations 
269  (e.g., CLINICAL PHARMACOLOGY, CLINICAL STUDIES).48 
270   
271  1.  Recommended Starting or Loading Dose or Dosage   
272   
273  If a dosing regimen includes a recommended starting or loading dose or dosage, this information 
274  should be included as part of the recommended dosage in the DOSAGE AND 
275  ADMINISTRATION section.  For example: 
276   
277  2.x Recommended Dosage and Administration 
278  The recommended dosage of DRUG-X is as follows: 
279   
280    Day 1:  Administer a single 50 mg dose by intravenous infusion over 30 minutes 
281  (loading dose) 
282    Day 2:  Administer the first 50 mg subcutaneous dose 
283    Day 9 and thereafter:  Administer 50 mg every week subcutaneously 
284   
285  2.  Recommended Titration Schedule  
286   
287  If the dosage of a drug is titrated (e.g., increased incrementally to achieve effectiveness while 
288  reducing the risk of adverse reactions), the DOSAGE AND ADMINISTRATION section must 
289  include the optimal method to titrate the dosage49 (i.e., recommended titration schedule) and 
 
46 See section IV.B.8. in this guidance. 
 
47 21 CFR 201.57(c)(3)(i)(I). 
 
48 For more information about recommendations concerning adherence with the dosage regimen, see sections IV.I. 
and J. of this guidance. 
 
49 21 CFR 201.57(c)(3)(i)(E). 
 
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290  should include specific dosage increments and the frequency and timing of the increments.  For 
291  example:50  
292   
293  2.x Recommended Dosage and Administration 
294  Administer DRUG-X as a continuous intravenous infusion over 48 hours as follows 
295  (dosage is based on ideal body weight): 
296   
297    Initiate at 50 mcg/kg/hour  
298    0 to 4 hours: 50 mcg/kg/hour 
299    4 to 8 hours: 100 mcg/kg/hour 
300    8 to 12 hours: 150 mcg/kg/hour 
301    12 to 48 hours: 200 mcg/kg/hour 
302   
303  3.  Maximum Recommended Dosage 
304   
305  The upper (dosage) limit beyond which safety and effectiveness have not been established, or 
306  beyond which increasing the dose does not result in increasing effectiveness (i.e., maximum 
307  recommended dosage), must be included in the DOSAGE AND ADMINISTRATION section 
308  as appropriate.51   
309   
310  4.  Maximum Recommended Duration  
311   
312  When treatment duration should be limited, the DOSAGE AND ADMINISTRATION section 
313  must include the usual duration of treatment.52  Examples of when treatment duration should be 
314  limited include when there are reasonable concerns about the safety or effectiveness of the drug 
315  with longer term use, when the disease or condition being treated is limited in duration, and 
316  when only short-term use of the drug is recommended to treat or prevent the disease or condition 
317  (e.g., when antibacterial drug is used to treat an uncomplicated urinary tract infection). 
318   
319  However, statements about the lack of longer term data should not be included in this section 
320  when all the following items apply: 
321   
322    The effectiveness of a drug for a chronic condition was evaluated only in short-term 
323  clinical trials, but these trials were of sufficient duration to support such an approval, and 
324  there are no known or anticipated and reasonable safety or effectiveness concerns with 
325  respect to longer term use.  
326   
 
50 This section must also contain specific direction on administration of the dosage form, if needed (see 21 CFR 
201.57(c)(3)(iv)).  For drugs administered intravenously, include the rate of administration and the recommended 
infusion duration, if needed, in the DOSAGE AND ADMINISTRATION section. 
 
51 21 CFR 201.57(c)(3)(i)(B). 
 
52 21 CFR 201.57(c)(3)(i)(F) and see 21 CFR 201.100(d)(1). 
 
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327    The drug is indicated for long-term use because of the chronic nature of the disease or 
328  condition (e.g., drugs for the treatment of hypertension).   
329   
330  In these circumstances, including statement(s) about the lack of longer term data in the 
331  DOSAGE AND ADMINISTRATION section may have the unintended effect of 
332  inappropriately encouraging health care practitioners to limit the duration of use of the drug.  
333  Information on the duration of use of the drug in the clinical trials should generally be discussed 
334  in the CLINICAL STUDIES section instead of this section.53   
335   
336  5.  Recommended Dosage in Pediatric Patients   
337   
338  The recommended dosage in pediatric patients for all approved pediatric indications must be 
339  included in the DOSAGE AND ADMINISTRATION section.54  If the recommended dosage is 
340  different between adults and pediatric patients, or among pediatric subpopulations, this section 
341  must identify the recommended dosages for each of the pediatric subpopulations55 (e.g., by 
342  pediatric age group, by weight or body surface area).  If a pediatric subpopulation should use 
343  only a specific age-appropriate dosage form (e.g., oral solution, tablets for oral suspension), this 
344  section should so state. 
345   
346  6.  Recommended Dosage in Geriatric Patients 
347   
348  If the recommended dosage is different between geriatric patients and adults younger than 65 
349  years of age, the DOSAGE AND ADMINISTRATION section must include the recommended 
350  dosage in geriatric patients.56  This section must include the recommended dosage in geriatric 
351  patients for all approved geriatric-specific indications.57   
352   
 
53 Also see the guidance for industry Clinical Studies Section of Labeling for Human Prescription Drug and 
Biological Products  Content and Format.   
 
54 21 CFR 201.57(c)(3)(i)(C) and (H) and 21 CFR 201.57(c)(9)(iv)(B), (C), and (D).  Also see the guidance for 
industry Pediatric Information Incorporated Into Human Prescription Drug and Biological Product Labeling 
(March 2019). 
 
55 Ibid. 
 
56 21 CFR 201.57(c)(3)(i)(C) and (H) and 21 CFR 201.57(c)(9)(v)(B)(3).  See also the draft guidance for industry 
Geriatric Information in Human Prescription Drug and Biological Product Labeling (September 2020).  When 
final, this guidance will represent the FDAs current thinking on this topic.   
 
57 21 CFR 201.57(c)(9)(v)(A).  A geriatric-specific indication is an indication only in geriatric patients (or a subset 
of the geriatric population) and not in younger adult patients.  See the draft guidance for industry Geriatric 
Information in Human Prescription Drug and Biological Product Labeling. 
 
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353  7.  Recommended Dosage for Fixed-Combination Drug Products and Co-Packaged 
354  Products  
355   
356  For the purposes of this guidance, a fixed-combination drug product (FCDP)58 is one in which 
357  two or more active ingredients are combined at a fixed dosage in a single dosage form.  For a 
358  FCDP, the DOSAGE AND ADMINISTRATION section should identify the recommended 
359  dosage of each drug or biologic component.  For example, for the fictitious FCDP, DRUG-X 
360  (active-ingredient-a, active-ingredient-b, and active-ingredient-c tablets): 
361   
362  2.x Recommended Dosage 
363  The recommended dosage of DRUG-X is one tablet (containing 500 mg of active-
364  ingredient-a, 250 mg of active-ingredient-b, and 100 mg of active-ingredient-c) orally once 
365  daily.   
366   
367  For co-packaged products,59 this section should identify the recommended dosage for each drug 
368  or biological product that is co-packaged.  Although FDA generally recommends avoiding 
369  including identifying characteristics of a drug in this section,60 such characteristics may be 
370  included in this section if necessary to facilitate safe use of the co-packaged product.  For 
371  example, for the fictitious co-packaged product, DRUG-X (active-ingredient-a tablets; active-
372  ingredient-b tablets):61 
373   
374  2.x Recommended Dosage 
375  DRUG-X is a co-packaged product containing active-ingredient-a tablets and active-
376  ingredient-b tablets.  The recommended oral dosage of DRUG-X is the following: 
377   
378    In the morning, take 100 mg of active-ingredient-a (one square blue tablet) and 50 mg 
379  of active-ingredient-b (one round yellow tablet)   
380    In the evening, take 100 mg of active-ingredient-a (one square blue tablet)    
381   
 
58 FCDPs include drug-drug combinations, biologic-biologic combinations, and drug-biologic combinations.  For the 
purposes of this guidance, the term FCDP does not refer to drug-device or biologic-device combination products. 
 
59 For the purposes of this guidance, a co-packaged drug product is a product that contains two or more separate 
drugs (e.g., two drugs, two biologics, one drug and one biologic) in their final dosage forms that are intended to be 
used together for a common or related therapeutic purpose and that are contained in a single package or unit.  For 
the purposes of this guidance, the term co-packaged products does not refer to a separate drug and device or a 
separate biologic and device contained in a single package or unit.  
 
60 See section II of this guidance. 
 
61 Data from human factor studies could be used to inform the development of the dosage- and administration-
related information for the co-packaged product. 
 
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382  8.  Administration Instructions Included With the Recommended Dosage    
383   
384  Certain administration instructions (e.g., route or routes of administration) should be included 
385  with the recommended dosage in the DOSAGE AND ADMINISTRATION section.62   
386   
387  For example, for orally administered drugs, this section should include specific instructions on 
388  how and when to administer the drug relative to the ingestion of food or food substances63 next 
389  to the recommended dosage.  If an orally administered drug should be administered on an empty 
390  stomach, this section should provide specific instructions on when to administer the drug relative 
391  to the ingestion of food or food substances (e.g., [[Include recommended dosage]] Administer 
392  DRUG-X on an empty stomach, at least 2 hours prior to or 2 hours after food).  If an orally 
393  administered drug can be administered with or without food, then this section should so state.64  
394  If there are additional pharmacokinetic details on the effects of food on the absorption of orally 
395  administered drugs, this section should include a cross-reference to the Pharmacokinetics 
396  subsection of the CLINICAL PHARMACOLOGY section (e.g., [[Include recommended 
397  dosage]].  Administer DRUG-X with or without food [see Clinical Pharmacology (12.3)]).   
398   
399  When the DOSAGE AND ADMINISTRATION section provides recommendations regarding 
400  the administration of an orally administered drug with food and those recommendations are not 
401  based on pharmacokinetic or pharmacodynamic data, this section should refer to appropriate 
402  sections of labeling that provide the explanation for the recommendation, if applicable.  For 
403  example, a recommendation to administer the drug with food to reduce the incidence of drug-
404  associated nausea might be based on clinical data comparing such administration to 
405  administration without food.  In that case, statements in the DOSAGE AND 
406  ADMINISTRATION section conveying this recommendation should refer another section where 
407  the information concerning nausea (the adverse reaction) would be further discussed (e.g., 
408  WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS). 
409   
410  9.  Recommended Monitoring for Effectiveness  
411   
412  Therapeutic drug monitoring is used for some drugs as part of the dosing regimen to achieve or 
413  maintain effectiveness or to reduce the risk of adverse reactions.  If they are established and 
414  clinically significant, efficacious or toxic concentration ranges and therapeutic concentration 
415  windows of the drug or its metabolites must be included in the DOSAGE AND 
416  ADMINISTRATION section.65  This section must also include information on when therapeutic 
 
62 For additional administration instructions that are required and recommended in the DOSAGE AND 
ADMINISTRATION section of labeling, see section IV.L. of this guidance. 
 
63 See the guidance for industry Assessing the Effects of Food on Drugs in INDs and NDAs  Clinical 
Pharmacology Considerations (June 2022). 
 
64 Ibid.  Although the DOSAGE AND ADMINISTRATION section should generally not include pertinent negative 
information, given that health care practitioners are particularly interested in food or food substance effects on the 
recommended dosage of orally administered drugs (if any), FDA recommends including information on the lack of a 
food effect (e.g., that the drug can be taken with or without food) in this section, as appropriate. 
 
65 21 CFR 201.57(c)(3)(i)(J). 
 
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417  drug concentration monitoring is necessary66 (including recommended frequency of monitoring) 
418  and should include dosage modifications based on levels and a cross-reference to other sections 
419  of the labeling that include the data that support these recommendations (e.g., CLINICAL 
420  PHARMACOLOGY, CLINICAL STUDIES).  For example: 
421   
422  2.x Recommended Therapeutic Drug Monitoring 
423  Obtain plasma trough concentrations of drugoxide after kidney transplant surgery and 
424  maintain drugoxide concentrations [see Clinical Pharmacology (12.3)] within the 
425  following therapeutic drug concentration windows:   
426   
427    Post-surgery to Month 1:  15 ng/mL to 20 ng/mL  
428    Month 1 to 2:  10 ng/mL to 15 ng/mL  
429    Month 2 to 6:  7.5 ng/mL to 10 ng/mL 
430    After Month 6:  5 ng/mL to 10 ng/mL 
431   
432  If specific monitoring is recommended during drug therapy to determine the lowest effective 
433  dosage (i.e., lowest dosage of DRUG-X needed to achieve or maintain effectiveness), this 
434  section should include information on the type of monitoring (e.g., the name of the assay or 
435  assays needed to detect drug levels), frequency of monitoring, and how to subsequently modify 
436  the dosage.67    
437    
438  If there is specific information on when to discontinue a drug because of lack of effectiveness, 
439  this section should include this information.  For example: 
440   
441  Discontinue DRUG-X if the patient experiences two or more recurrences of Condition-A 
442  while taking the recommended dosage. 
443   
444  C.  Other Therapy Used Before, During, or After Drug Treatment or 
445  Administration 
446   
447  1.  Other Therapy Used Before Drug Administration   
448   
449  If there is important information about administering other drugs before initiating the subject 
450  drug,68 this information should be included in the DOSAGE AND ADMINISTRATION section.  
451  For example, if premedication is recommended to minimize potential hypersensitivity reactions, 
452  this section should describe the premedication regimen and include a cross-reference to the 
 
66 Ibid. 
 
67 Information on the time to onset of efficacy, if available, should generally be included in the CLINICAL 
STUDIES section, as appropriate, rather than the DOSAGE AND ADMINISTRATION section.  See the guidance 
for industry Clinical Studies Section of Labeling for Human Prescription Drug and Biological Products  Content 
and Format.  Also see section IV.D.1. of this guidance for recommendations on monitoring that are needed during 
drug therapy to modify the dosage or administration to reduce the risk of adverse reactions. 
 
68 For the purposes of this guidance, the term subject drug refers to the drug for which the labeling is being 
developed. 
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453  detailed discussion of hypersensitivity reactions elsewhere in labeling (e.g., WARNINGS AND 
454  PRECAUTIONS, ADVERSE REACTIONS).   
455   
456  2.  Other Therapy Used During or After Drug Treatment or Administration   
457   
458  If the drug is indicated for use only in conjunction with concomitant therapy,69 the DOSAGE 
459  AND ADMINISTRATION section should identify the concomitant therapy (e.g., concomitant 
460  drug or drug class, surgery, or behavior modification).  If a drug must be given at a specific time 
461  relative to the concomitant therapy for effectiveness, this section should include this information 
462  and cross-reference to other sections of the labeling that summarize the data supporting this 
463  recommendation, if applicable (e.g., CLINICAL PHARMACOLOGY).  FDA generally 
464  recommends including such information with the recommended dosage. 
465   
466  If there are concomitant drugs recommended for use during treatment with the subject drug or 
467  other drugs recommended for use after administration of the subject drug or after treatment with 
468  the subject drug to reduce the risk of adverse reactions (e.g., antiemetics, antimicrobials, 
469  corticosteroids), this section should include this information and, as appropriate, should cross-
470  reference to the detailed discussion of these adverse reactions elsewhere in labeling (e.g., 
471  WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS).  If the subject drug needs to 
472  be given at a specific time relative to the timing of a recommended concomitant drug to prevent 
473  or reduce the risk of toxicity of the drug, the DOSAGE AND ADMINISTRATION section 
474  should include this information and cross-reference other sections that provide support for this 
475  recommendation (e.g., CLINICAL PHARMACOLOGY section). 
476   
477  D.  Dosage Modifications 
478   
479  When providing information on dosage modifications in the DOSAGE AND 
480  ADMINISTRATION section, to reduce the risk of medication errors, FDA generally 
481  recommends providing the precise modified dosage rather than the percentage of the original 
482  recommended dosage (e.g., state Reduce the DRUG-X dosage to 1 mg intravenously once 
483  daily instead of Reduce the DRUG-X dosage by 50%).   
484   
485  1.  Dosage Modifications Intended to Reduce the Risk of Adverse Reactions 
486   
487  If there are recommendations on dosage modifications (e.g., dosage reduction, dosage 
488  interruption, or permanent discontinuation) intended to reduce the risks of adverse reactions, this 
489  information should be included in the DOSAGE AND ADMINISTRATION section.  This 
490  section should cross-reference the detailed discussion of the adverse reactions in other sections 
491  of labeling, as appropriate (e.g., WARNINGS AND PRECAUTIONS, ADVERSE 
492  REACTIONS).  Detailed descriptions of the clinically significant adverse reactions (or the steps 
493  to take to prevent, mitigate, monitor for, or manage the adverse reactions that are not related to 
 
69 If the drug is used for an indication only in conjunction with a primary mode of therapy (e.g., diet, surgery, 
behavior changes, or some other drug), the INDICATIONS AND USAGE section must include a statement that the 
drug is indicated as an adjunct to that mode of therapy.  See 21 CFR 201.57(c)(2)(i)(A). 
 
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494  dosage or administration modifications) should be described in the WARNINGS AND 
495  PRECAUTIONS section rather than in the DOSAGE AND ADMINISTRATION section.70   
496   
497  Information on tests, procedures, and/or evaluations that are needed during treatment with the 
498  drug to modify the dosage or administration due to adverse reactions should be included in this 
499  section.71  However, if such tests, procedures, and/or evaluations will not result in a modification 
500  to the recommended dosage or administration, this information should generally appear 
501  elsewhere in labeling (e.g., in the WARNINGS AND PRECAUTIONS section).  For information 
502  on tests, procedures, and/or evaluations needed before drug initiation, see section IV.A. of this 
503  guidance.  
504   
505  2.  Dosage Modifications for Drug Interactions  
506   
507  If there are dosage modifications for drug interactions with other drugs, classes of drugs, or 
508  foods (e.g., dietary supplements, grapefruit juice),72 the DOSAGE AND ADMINISTRATION 
509  section must include this information, as appropriate,73 and should cross-reference to a detailed 
510  discussion of the drug interactions in other sections of labeling (e.g., DRUG INTERACTIONS, 
511  CLINICAL PHARMACOLOGY).  More specifically, when there is sufficient information to 
512  support specific recommendations to modify the dosage or administration of the subject drug 
513  (e.g., dosage reduction, alteration of the timing of a dose relative to dosing of another drug) to 
514  reduce the risk of a drug interaction, the specific recommendations should be included in the 
515  DOSAGE AND ADMINISTRATION section.  When there is not enough information to support 
516  a specific dosage or administration modification for the subject drug, the drug interaction should 
517  ordinarily not be discussed in this section.   
518   
519  FDA generally recommends that contraindications or statements about when use is inadvisable 
520  not appear in this section.74  However, if dosage modification of the subject drug is 
521  recommended when it is used with a subgroup of a specific drug interacting class75 (e.g., the 
522  subgroup of CYP3A inhibitors that are moderate CYP3A inhibitors), then: 
523   
 
70 See 21 CFR 201.57(c)(6)(i) and the guidance for industry Warnings and Precautions, Contraindications, and 
Boxed Warning Sections of Labeling for Human Prescription Drug and Biological Products - Content and Format. 
 
71 See section IV.B.9. of this guidance for recommendations on specific monitoring during drug therapy to 
determine the lowest effective dosage or to discontinue the drug due to inadequate effectiveness. 
 
72 21 CFR 201.57(c)(8)(i).   
 
73 21 CFR 201.57(c)(3)(i)(H). 
 
74 If a use is contraindicated or inadvisable, this information is included in other sections of labeling.  Also see 
section II of this guidance. 
 
75 For purposes of this guidance, we use the term drug interacting class to mean a group of drugs and/or foods that 
all share a specific characteristic that is relevant to clinically significant drug interaction(s) (e.g., all members of the 
class have in common a particular effect on drug metabolism).  In the case of drugs, the shared characteristic that 
identifies the drug interacting class may be unrelated to the drugs therapeutic class.   
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524    This section should generally provide recommendations for use of the subject drug for 
525  the remaining subgroups in the drug interacting class (e.g., strong CYP3A inhibitors) for 
526  completeness, including subgroups in which concomitant use is contraindicated or 
527  inadvisable as well as subgroups in which there are no recommended dosage 
528  modifications. 
529   
530    It is generally unnecessary to include a statement in this section that no dosage 
531  modification is needed for a remaining drug interacting class that rarely requires dosage 
532  modifications (e.g., weak CYP3A inhibitors).    
533    
534  For example:  
535   
536  2.x Dosage Modifications for CYP3A Inhibitors 
537  Avoid concomitant use with strong CYP3A inhibitors.  Reduce the DRUG-X dosage to 20 
538  mg once daily when used concomitantly with a moderate CYP3A inhibitor [see Drug 
539  Interactions (7.x)]. 
540   
541  If there are dosage modifications for two or more drugs, classes of drugs, or foods, consider 
542  including the dosage modifications in one subsection within this section with appropriate 
543  headings (e.g., CYP3A Inducers and P-glycoprotein Inhibitors headings appear under 2.x 
544  Dosage Modifications for Drug Interactions). 
545   
546  The description and mechanism of a drug interaction, study findings, clinical implications, and 
547  practical instructions for preventing or managing the drug interaction (except for dosage and 
548  administration modifications of the subject drug) should not be included in this section.  If there 
549  are recommended dosage modifications of the concomitant drug, this information should also not 
550  be included in this section; rather, this section should include a cross-reference to this 
551  information in the DRUG INTERACTIONS section, as appropriate.  
552   
553  E.  Dosage in Patients With Renal Impairment 
554   
555  If the dosage in patients with renal impairment is different from the recommended dosage in 
556  patients with normal kidney function, the DOSAGE AND ADMINISTRATION section must 
557  include the dosage in the applicable renal impairment subpopulation(s).76,77   
558   
559  If there are dosage differences for at least one of the renal impairment subpopulation(s) (e.g., 
560  patients with an estimated glomerular filtration rate (GFR) less than 30 mL/minute) compared 
561  with patients with normal kidney function, dosage recommendations should generally be 
562  provided for all subpopulations within the renal impairment population (i.e., patients with 
 
76 21 CFR 201.57(c)(3)(i)(C) and (H).  
 
77 If a subsection providing dosage information in patients with renal impairment is included in the DOSAGE AND 
ADMINISTRATION section, FDA recommends using a subsection heading such as Recommended Dosage in 
Patients with Renal Impairment rather than Renal Impairment because the latter heading is typically a reserved 
subsection heading in the USE IN SPECIFIC POPULATIONS section to facilitate coding of structured product 
labeling.   
 
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563  estimated GFR less than 90 mL/minute) in this section, including renal impairment 
564  subpopulations in which the: 
565   
566    Use of the drug is contraindicated or inadvisable78 
567   
568    Recommended dosage is the same as the recommended dosage in patients with normal 
569  kidney function  
570   
571  The example below is for DRUG-X, approved only in adult patients,79 whose recommended 
572  dosage in patients with normal kidney function is 2 grams administered intravenously every 8 
573  hours.  The estimated GFR bands are based on the data from the clinical studies, not on a renal 
574  impairment classification scheme.80  
575   
576  2.x Recommended Dosage in Patients With Renal Impairment 
577  The recommended dosage of DRUG-X in patients with renal impairment with a stable 
578  estimated GFR is described in Table 1 [see Use in Specific Populations (8.6) and Clinical 
579  Pharmacology (12.3)]. Administer each intravenous infusion over 3 hours.  
580   
581  Table 1. Recommended DRUG-X Dosage in Patients With Renal Impairment 
582   
Estimated GFR*  Dose  Frequency 
5089 mL/minute  2 grams   Every 8 hours 
2549 mL/minute  1.5 grams  Every 8 hours 
1524 mL/minute  1.5 grams  Every 12 hours 
<15 mL/minute or receiving intermittent hemodialysis**   1 gram  Every 12 hours 
583  * If the estimated GFR (eGFR) for an adult patient is calculated using an equation standardized to a body 
584  surface area value of 1.73 m2 (reported in units of mL/minute/1.73 m2), then multiply the standardized eGFR 
585  value by the patients body surface area and divide by 1.73 to obtain the eGFR in units of mL/minute.  
586  Finally, use the eGFR in units of mL/minute to determine the recommended dose and frequency. 
587  ** For adult patients with kidney failure receiving intermittent hemodialysis, administer DRUG-X after 
588  dialysis.  
589   
 
78 If the use of the drug is contraindicated or inadvisable in all renal impairment subpopulations, then this 
information should be included in other sections of the labeling, as appropriate (e.g., BOXED WARNINGS, 
CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, USE IN SPECIFIC POPULATIONS), rather than 
the DOSAGE AND ADMINISTRATION section (see section II of this guidance).   
 
79 If a drug is indicated for use only in adults (not pediatric patients), it is not necessary to include the term adults in 
the DOSAGE AND ADMINISTRATION section. 
 
80 For additional information on how to assess renal function, see section IV.A., Determination of Renal Function, in 
the draft guidance for industry Pharmacokinetics in Patients with Impaired Renal Function  Study Design, Data 
Analysis, and Impact on Dosing (September 2020).  When final, this guidance will represent the FDAs current 
thinking on this topic. 
 
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590  The example below is for DRUG-X, whose recommended dosage in pediatric patients with 
591  normal kidney function is 40 mg/kg orally once daily.  The eGFR bands reflect how the drug was 
592  dosed in the clinical studies, not on a renal impairment classification scheme.81 
593   
594  2.x Recommended Dosage in Pediatric Patients With Renal Impairment 
595  The recommended dosage of DRUG-X in pediatric patients with renal impairment with a 
596  stable estimated GFR is described in Table 2 [see Use in Specific Populations (8.4, 8.6) 
597  and Clinical Pharmacology (12.3)]. 
598   
599  Table 2. Recommended DRUG-X Dosage in Pediatric Patients With Renal 
600  Impairment 
601   
Estimated GFR*  Dosage** 
6089 mL/minute/1.73 m2  30 mg/kg orally once daily 
3059 mL/minute/1.73 m2  20 mg/kg orally once daily 
1529 mL/minute/1.73 m2  10 mg/kg orally once daily 
<15 mL/minute/1.73 m2 or receiving peritoneal 
Use is not recommended 
dialysis or hemodialysis   
602  * Estimate GFR using an equation validated for use in the appropriate pediatric age range 
603  ** Dosage based on actual body weight. 
604   
605  Furthermore, in this section, FDA recommends the following, as appropriate: 
606   
607    When providing a recommended dosage in patients with renal impairment receiving 
608  dialysis, specify the dialysis modality or modalities (e.g., intermittent hemodialysis, 
609  peritoneal dialysis, continuous renal replacement therapy) instead of using the 
610  nonspecific term dialysis. 
611   
612    When providing recommendations for patients receiving intermittent hemodialysis, 
613  specify the timing of drug administration in relation to hemodialysis (e.g., When 
614  administered on a hemodialysis day, administer DRUG-X after hemodialysis). 
615   
616    Avoid using the terms end-stage renal disease or ESRD because these terms may not 
617  accurately describe the degree of renal impairment given that these terms can include 
618  patients with kidney failure as well as those with a kidney transplant with normal kidney 
619  function. 
620   
 
81 When providing dosage recommendations in pediatric patients with renal impairment in the DOSAGE AND 
ADMINISTRATION section, FDA recommends including the following or similar statement given that widely 
available eGFR equations for adult patients are generally not appropriate for use in pediatric patients:  Estimate 
GFR using an equation validated for use in the appropriate pediatric age range.  See the draft guidances for industry 
Pharmacokinetics in Patients with Impaired Renal Function  Study Design, Data Analysis, and Impact on Dosing 
and General Clinical Pharmacology Considerations for Pediatric Studies for Drugs and Biological Products 
(December 2014).  When final, these guidances will represent the FDAs current thinking on these topics. 
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621  F.  Dosage in Patients With Hepatic Impairment 
622   
623  If the dosage in patients with hepatic impairment (e.g., mild, moderate, or severe) caused by 
624  chronic liver disease is different from the recommended dosage in patients with normal hepatic 
625  function, the DOSAGE AND ADMINISTRATION section must include the dosage in the 
626  applicable hepatic impairment subpopulations.82  If the dosage in patients with hepatic 
627  impairment is included,83 this section should identify the method used for classifying hepatic 
628  function (e.g., the Child-Pugh Classification).84 
629   
630  If there are dosage differences for at least one of the hepatic impairment subpopulations (e.g., 
631  Child-Pugh C) compared with patients with normal hepatic function, recommendations for use of 
632  the drug should generally be provided for all the hepatic impairment subpopulations (e.g., Child-
633  Pugh A, B, and C) in this section, including hepatic impairment subpopulations in which the: 
634   
635    Use of the drug is contraindicated or inadvisable85  
636   
637    Recommended dosage is the same as the recommended dosage in patients with normal 
638  hepatic function 
639   
640  G.  Dosage in Other Specific Populations  
641   
642  If the recommended dosage in other specific patient populations (e.g., males and females, 
643  patients defined by certain genetic characteristics86 (such as patients who are CYP2D6 poor 
644  metabolizers), postpartum patients, pregnant patients, racial or ethnic subgroups87) is different 
 
82 21 CFR 201.57(c)(3)(i)(C) and (H). 
 
83 If a subsection providing dosage information in patients with hepatic impairment is included in the DOSAGE 
AND ADMINISTRATION section, FDA recommends using a subsection heading such as Recommended Dosage in 
Patients with Hepatic Impairment rather than Hepatic Impairment because the latter heading is typically reserved for 
a subsection heading in the USE IN SPECIFIC POPULATIONS section to facilitate coding of structured product 
labeling.   
 
84 Weissenbaum, K, 2019, Hepatic Encephalopathy:  Definition, Clinical Grading and Diagnostic Principles, Drugs, 
79(Suppl 1):S5S9; Tsoris, A and C Marlar, 2021, Use of the Child Pugh Score in Liver Disease, StatPearls, epub 
ahead of print, last updated on March 22, 2021, available at https://www.ncbi.nlm.nih.gov/books/NBK542308/. 
 
85 If the use of the drug is contraindicated or inadvisable in all hepatic impairment subpopulations, then this 
information should be included in other sections of the labeling, as appropriate (e.g., BOXED WARNING, 
CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, USE IN SPECIFIC POPULATIONS), rather than 
the DOSAGE AND ADMINISTRATION section (see section II of this guidance).   
 
86 See the guidance for industry Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical Studies 
and Recommendations for Labeling (January 2013). 
 
87 See the guidance for industry and FDA staff Collection of Race and Ethnicity Data in Clinical Trials (October 
2016). 
 
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645  from the recommended dosage in the general population, the DOSAGE AND 
646  ADMINISTRATION section must include the dosage in such specific patient populations.88,89  
647   
648  H.  Information About Switching90 and Substitution 
649   
650  1.  Switching to the Subject Drug 
651   
652  If there is adequate information to support how to switch to the subject drug from other drugs 
653  (e.g., drugoxide tablets to drugoxide extended-release tablets, intravenous heparin to an oral 
654  anticoagulant) and this information is important for the safety or effectiveness of the subject 
655  drug, the DOSAGE AND ADMINISTRATION section should include this information.   
656   
657  2.  Cautionary Statements Relating to Substitution 
658   
659  If applicable to the subject drug, the DOSAGE AND ADMINISTRATION section should advise 
660  against substitution of one drug for another drug (e.g., substitution of the subject drug for another 
661  drug, substitution of another drug for the subject drug) that would lead to harm or loss of 
662  effectiveness.91  In this situation, FDA recommends the use of phrases such as do not substitute 
663  DRUG-X for [insert drug name] [see Warnings and Precautions (5.x)]. 
664   
665  FDA recommends avoiding the term interchangeable in this section of labeling because it could 
666  create confusion with the same term which is generally used in an interchangeable biosimilarity 
667  statement in the Highlights of Prescribing Information of interchangeable biosimilar 
668  products.92,93  For example, this section should not state that drugoxide liposome injection and 
669  drugoxide injection are not interchangeable. 
670   
 
88 21 CFR 201.57(c)(3)(i)(C) and (H). 
 
89 See section IV.B.5., B.6., E., and F. of this guidance for information about the recommended dosage in pediatric 
patients, geriatric patients, patients with renal impairment, and patients with hepatic impairment, respectively. 
 
90 The term switching here does not refer to alternating or switching as described in section 351(k)(4)(B) of the PHS 
Act. 
 
91 When certain dosage- and administration-related information is particularly critical to the safe and effective use of 
the drug this information should appear as the first information presented within the DOSAGE AND 
ADMINISTRATION section.  See section IV.A. of this guidance. 
 
92 See answer to Question I.28 in the draft guidance for industry Biosimilarity and Interchangeability: Additional 
Draft Q&As on Biosimilar Development and the BPCI Act  (November 2020).  When final, this guidance will 
represent the FDAs current thinking on this topic. 
 
93 See also sections 351(i)(3) and 351(k)(4) of the PHS Act. 
 
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671  I.  Recommendations Regarding Missed Dose(s)  
672   
673  If there is adequate information to support dosage or administration recommendations about 
674  what to do in the event of missed dose(s), the DOSAGE AND ADMINISTRATION section 
675  should include this information. 
676   
677  J.  Recommendations in Event of Vomiting After Oral Drug Administration 
678   
679  If there is adequate information to support dosage or administration recommendations about what 
680  to do if vomiting occurs after oral drug administration, the DOSAGE AND ADMINISTRATION 
681  section should include this information. 
682   
683  K.  Recommendations for Drug Discontinuation or Dosage Reduction When 
684  There Are Risks of Withdrawal  
685   
686  If there are risks of withdrawal upon abrupt discontinuation or dosage reduction of a drug (e.g., 
687  known withdrawal syndrome),94 the DOSAGE AND ADMINISTRATION section should 
688  include instructions for drug discontinuation or dosage reduction, as applicable, including a 
689  specific tapering regimen, if available, and should cross-reference additional information about 
690  withdrawal reactions in other sections of labeling (e.g., WARNINGS AND PRECAUTIONS, 
691  DRUG ABUSE AND DEPENDENCE).  For example: 
692   
693  2.x Discontinuation of DRUG-X  
694  ... When discontinuing DRUG-X, decrease the daily oral dosage by 5 mg once weekly 
695  until discontinued [see Drug Abuse and Dependence (9.3)]. 
696   
697  A detailed description of the withdrawal syndrome after abrupt discontinuation or dosage 
698  reduction of a drug (except for the specific instructions for drug discontinuation or dosage 
699  reduction) should not be included in this section.95 
700   
701  L.  Additional Preparation and Administration Instructions 
702   
703  The DOSAGE AND ADMINISTRATION section:96 
704   
 
94 See the draft guidance for industry Drug Abuse and Dependence Section of Labeling for Human Prescription 
Drug and Biological Products  Content and Format (July 2019).  When final, this guidance will represent the 
FDAs current thinking on this topic. 
 
95 The Dependence subsection in the DRUG ABUSE AND DEPENDENCE section must provide details on the 
effects of abrupt withdrawal. See 201.57(c)(10)(iii).  That subsection also should summarize signs and symptoms of 
withdrawal after abrupt discontinuation or dosage reduction of a drug, and additional sections may discuss the 
clinical effects of dependence (e.g., WARNINGS AND PRECAUTIONS).  See the draft guidance for industry Drug 
Abuse and Dependence Section of Labeling for Human Prescription Drug and Biological Products - Content and 
Format. 
 
96 For other required and recommended administration or preparation instructions, see sections IV.A. and B.8. of this 
guidance.   
 
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705    Must contain specific directions for preparation of the drug97 before administration, if 
706  needed (e.g., reconstitution of a lyophilized powder, dilution) 
707   
708    Should identify the compatible diluents (including the volume of diluent required for 
709  reconstitution).  FDA recommends the use of the strength and the established name of the 
710  diluent in this section.  For example, use 0.9% Sodium Chloride Injection instead of 
711  normal saline or saline and use 5% Dextrose Injection instead of dextrose in 
712  sterile water  
713   
714    Must include the strength of the final dosage solution, when prepared according to 
715  instructions, in terms of milligrams of active ingredient per milliliter of reconstituted 
716  solution, unless another measure of the strength is more appropriate.98  In addition, with 
717  respect to diluted solutions, this section should also include the strength of the final 
718  dosage form (e.g., oral solution, oral suspension) in terms of milligrams of active 
719  ingredient per milliliter of diluted solution (unless another measure of the strength is 
720  more appropriate).  If a drug requires: 
721   
722    Only reconstitution before administration, this section should identify the volume of 

723  the reconstituted solution to be withdrawn and administered. 
724     
725    Only dilution before administration, this section should identify the volume of the 

726  diluted solution to be withdrawn and administered. 
727   
728    Both reconstitution and dilution before administration, this section should identify the 

729  volume of the reconstituted solution to be withdrawn (for dilution) and also identify 
730  the volume of the diluted solution to be withdrawn and administered.     
731   
732  This section must also contain specific directions on (i.e., instructions for) the administration of 
733  the dosage form, if needed.99  For example, for drugs administered as follows: 
734   
735    Intravenously, include the rate of administration (e.g., infusion rate in milligrams per 
736  minute) and recommended infusion duration, if needed.100  For an intravenous push or 
737  bolus administration, include the duration of the injection (e.g., administer over X 
738  minutes), if needed.101  
 
97 21 CFR 201.57(c)(3)(iv). 
 
98 21 CFR 201.57(c)(3)(iv).  See also United States Pharmacopeia (USP) General Chapter <7> Labeling.  Applicable 
provisions of USP General Chapters numbered below 1000 are requirements for compendial drug products if 
referenced in an applicable USP/National Formulary (NF) monograph, or if they are made applicable through USP 
General Notices for products with USP/NF monographs. See, for example, sections 501(b) and 502(g) of the FD&C 
Act.  Otherwise, they are recommendations. 
 
99 21 CFR 201.57(c)(3)(iv). 
 
100 Ibid. 
 
101 See 21 CFR 201.57(c)(3)(iv). 
 
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Draft  Not for Implementation 
739   
740    Intramuscularly or subcutaneously, state the recommended injection site(s) (e.g., gluteal, 
741  deltoid) and the rotation schedule, if needed.   
742   
743    If more than one injection is needed to achieve a full dose, provide specific 

744  administration instructions (e.g., Administer the second of the two subcutaneous 
745  injections at least two inches from the site of the first subcutaneous injection).   
746   
747    If the injection depth is important for administration or the injection duration is 

748  lengthy (e.g., two minutes or longer), include the recommended injection depth or the 
749  recommended duration of the injection, respectively. 
750   
751  If there are known clinically significant adverse reactions or risks associated with inappropriate 
752  administration, this section should briefly state the inappropriate administration that is 
753  inadvisable and should generally cross-reference to other sections for additional details (e.g., 
754  WARNINGS AND PRECAUTIONS).  For example, Do not administer intrathecally [see 
755  Warnings and Precautions (5.x)].102 
756   
757  If a pediatric subpopulation should not self-administer a drug,103 the DOSAGE AND 
758  ADMINISTRATION section should include this information. 
759   
760  1.  Preparation and Administration Instructions for Parenteral Products  
761   
762  If specific containers (e.g., glass, plastic, non-polyvinyl chloride) or devices (e.g., tubing, 
763  needles, syringes) are needed for preparation or administration of a parenteral product,104 the 
764  DOSAGE AND ADMINISTRATION section should include this information.  If the 
765  container(s) or device(s) will not be approved under the new drug application or the biologics 
766  license application, the types of container(s) or device(s) should typically be described in this 
767  section in general terms rather than identifying a specific manufacturers product.  If there are 
768  data that provide important incompatibility information about the use of the drug with specific 
769  containers or devices, this section should include information on which containers or devices are 
770  incompatible with the drug.   
771   
 
102 If such information is particularly critical to the safe and effective use of the drug, this information should appear 
as the first information presented within the DOSAGE AND ADMINISTRATION section.  See section IV.A. of this 
guidance. 
 
103 Circumstances when pediatric patients should not self-administer the drug include when human factors testing 
did not evaluate self-administration in pediatric patients. 
 
104 For the purposes of this guidance, parenteral is a general route of administration that is characterized by injection 
through the skin or other external boundary tissue or implantation within the body.  Specific parenteral routes 
include intra-arterial, intra-articular, intracisternal, intramuscular, intraocular, intrathecal, intravenous, 
intraventricular, and subcutaneous.  See USP General Chapter <1151> Pharmaceutical Dosage Forms. 
 
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Draft  Not for Implementation 
772  This section must include essential information on drug incompatibilities if the drug is mixed in 
773  vitro with other diluents105 and should include the explanation of the incompatibility.   
774   
775  For parenteral products, this section must include the following verbatim statement:106  
776   
777  Parenteral drug products should be inspected visually for particulate matter and 
778  discoloration prior to administration, whenever solution and container permit.   
779   
780  When appropriate, this section should include a statement on when to discard a parenteral 
781  product (e.g., Discard unused reconstituted solution) (also see section IV.L.3. and L.4. and M. 
782  of this guidance).107   
783   
784  If a parenteral product needs to be filtered before administration, this section should identify the 
785  appropriate filter(s) and filter pore size (e.g., low-protein binding, 0.2 micron, in-line filter).   
786   
787  2.  Administration Instructions for Certain Dosage Forms    
788   
789  For certain dosage forms, the DOSAGE AND ADMINISTRATION section should include 
790  recommended administration instructions that are important for safe and effective use of the 
791  drug.  For example: 
792   
793    For modified-release dosage forms (e.g., extended-release tablets, delayed-release 
794  tablets), if there are: 
795   
796    Data that demonstrate a risk associated with manipulating the modified-release 

797  product, this section should include the following (or similar) statement: Swallow 
798  tablets whole.  Do not split, crush, or chew the extended-release tablets [see Clinical 
799  Pharmacology (12.3)]. 
800   
801    No data to inform the risk associated with manipulating the modified-release product 

802  but there is concern that modification may alter the drugs safety or effectiveness, this 
803  section should generally provide a rationale.  For example: Swallow tablets whole.  
804  Avoid splitting, crushing, or chewing the extended-release tablets because doing so 
805  may compromise the extended-release characteristics, effectiveness, or safety of 
806  DRUG-X. 
807   
 
105 21 CFR 201.57(c)(3)(iv). See section IV.L.8 of this guidance for recommendations regarding information on 
drug incompatibilities if the drug is mixed in vitro with other drugs.  
 
106 Ibid. 
 
107 Discard statements in labeling should be supported by appropriate data on when to stop using an injectable 
medical product.  See USP General Chapter <7>.  Also see the guidance for industry Selection of the Appropriate 
Package Type Terms and Recommendations for Labeling Injectable Medical Products Packaged in Multiple-Dose, 
Single-Dose, and Single-Patient-Use Containers for Human Use (October 2018). 
 
  26  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
808    For system dosage forms (a drug-containing delivery system that controls the release rate 
809  of the drug from the system by diffusion kinetics, active transport, or other means), this 
810  section should provide the rate of release and the total duration of the drug release,108 and 
811  instructions for application, rotation, and removal when applicable. 
812   
813    For chewable tablets, this section should include the following (or similar) statement to 
814  inform the health care practitioner that chewable tablets must always be chewed or 
815  crushed:109  Chew or crush DRUG-X completely before swallowing.  Do not swallow 
816  the chewable tablets whole.   
817   
818    For tablets for oral suspension or tablets for oral solution, this section should include a 
819  statement to inform the health care practitioner that these dosage forms should be 
820  dispersed in liquid and, if applicable, can also be swallowed whole or chewed.110  
821   
822  3.  Preparation of a Product Stored in the Refrigerator or Freezer  
823   
824  If applicable, the DOSAGE AND ADMINISTRATION section should discuss the time needed 
825  to allow a refrigerated or frozen product (supplied or prepared) to warm to room temperature 
826  before use.  For example: 
827   
828  2.x Preparation Instructions 
829  Remove the DRUG-X vial from the refrigerator and allow the vial to sit for 30 to 40 
830  minutes at room temperature 20oC to 25oC (68oF to 77oF) before use.  Do not use an 
831  external heat source to heat the product because heat may damage the product. 
832   
833  If a refrigerated reconstituted or diluted product is removed from the refrigerator, this section 
834  should include recommendations on the length of time the reconstituted or diluted product can be 
835  kept at room temperature before use and appropriate discard instructions.  For example: 
836   
837  2.x Preparation Instructions 
838  After removal of the DRUG-X reconstituted solution from the refrigerator, use the 
839  reconstituted solution within 2 hours or discard.    
840   
 
108 See Appendix A Dosage Form Terms for Use in Human Drug Product Labeling in the draft guidance for 
industry Product Title and Initial U.S. Approval in the Highlights of Prescribing Information for Human 
Prescription Drug and Biological Products  Content and Format (January 2018).  See also the draft guidance for 
industry Transdermal and Topical Delivery Systems  Product Development and Quality Considerations (November 
2019) for more information about the expression of strength and quality considerations that should be considered 
when supporting the information that is included in the DOSAGE AND ADMINISTRATION section.  When final, 
these guidances will represent the FDAs current thinking on these topics.  
 
109 See the guidance for industry Quality Attribute Considerations for Chewable Tablets (August 2018). 
 
110 See USP Nomenclature Guidelines, available at https://www.usp.org/sites/default/files/usp/document/usp-
nomenclature-guidelines.pdf. 
 
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841  4.  Preparation and Storage of Pharmacy Bulk Packages   
842   
843  For products supplied as pharmacy bulk packages (PBPs), the DOSAGE AND 
844  ADMINISTRATION section should describe proper techniques for preparation of the product 
845  and the time frame during which the PBP may be used after initial entry of the container 
846  (provided it is held under labeled storage conditions).111,112  This section should also state that 
847  the PBP is not for direct infusion.  For example: 
848   
849  2.x Preparation and Storage of the Pharmacy Bulk Package 
850  DRUG-X 1,000 mL is supplied as a pharmacy bulk package (PBP) for admixing only and 
851  is not for direct intravenous infusion.  Before administration, DRUG-X must be transferred 
852  to a separate container, prepared, and used as an admixture.  
853   
854    Use only in a suitable work area, such as a laminar flow hood or an equivalent clean 
855  air compounding area. 
856    Inspect the DRUG-X PBP for particulate matter. 
857    Penetrate the bulk PBP closure only one time using a suitable sterile transfer device 
858  or dispensing set that allows measured dispensing of the contents.  
859    Once the container closure is penetrated, transfer the PBP contents within 4 hours and 
860  discard any unused contents. 
861   
862  5.  Preparation/Administration of Solid Oral Dosage Forms With Qualified Liquids 
863  or Soft Foods 
864   
865  If a liquid or soft food is qualified as a vehicle to be used for the administration of a solid oral 
866  dosage form (e.g., capsules, granules, tablets), the DOSAGE AND ADMINISTRATION section 
867  should include directions for using the recommended liquid or soft food vehicle to administer the 
868  drug.113  For example:   
869   
870  2.x Preparation and Administration Instructions 
871  Swallow DRUG-X whole.  However, for patients who have difficulty swallowing capsules: 
872   
873    Carefully open the capsule and sprinkle the entire contents of the capsule onto room 
874  temperature applesauce (between a teaspoonful (5 mL) and a tablespoonful (15 mL)).  
875    Stir the mixture for 10 seconds. 
 
111 USP General Chapter <7>. 
 
112 For products supplied as imaging bulk packages (IBPs), the DOSAGE AND ADMINISTRATION section should 
describe proper techniques for preparation of the product and the time frame during which the IBP may be used after 
initial entry of the container (provided it is held under labeled storage conditions).  See USP General Chapter <659> 
Packaging and Storage Requirements for more information about IBPs. 
 
113 See the draft guidance for industry Use of Liquids and/or Soft Foods as Vehicles for Drug Administration: 
General Considerations for Selection and In Vitro Methods for Product Quality Assessments (July 2018).  When 
final, this guidance will represent the FDAs current thinking on this topic. 
 
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876    Consume the entire mixture within 30 minutes of mixing.  Do not save the mixture 
877  for later use. 
878   
879  6.  Preparation and Administration of Oral Dosage Forms Via Enteral Tubes   
880   
881  If there are adequate data that support the use of an oral dosage form (e.g., capsules, granules, 
882  oral suspensions, powders, and tablets) via enteral tube, the DOSAGE AND 
883  ADMINISTRATION section should include information on the preparation and administration 
884  of the oral dosage form via the enteral tube (e.g., nasogastric, gastrostomy, jejunostomy).  This 
885  section should include, as applicable, the characteristics of the recommended enteral tube, drug 
886  product and enteral tube preparation instructions, recommended administration instructions, and 
887  instructions on maintenance of the enteral tube following administration.114    
888   
889  If specific data exist to warrant a recommendation to not administer an oral dosage form via 
890  enteral tube, then this section should so state and provide a brief rationale, if appropriate.115 
891   
892  7.  Instructions to Avoid Harm Related to Drug Handling and Administration 
893   
894  If mishandling a drug may have serious consequences for the patient or others who may interact 
895  with the product (e.g., flammable products, hazardous drugs,116 radioactive products, products 
896  with latex, transdermal systems), the DOSAGE AND ADMINISTRATION section should 
897  include instructions to avoid harm related to drug handling and administration.  
898   
899  For hazardous drugs, this section (as well as the HOW SUPPLIED/STORAGE AND 
900  HANDLING section) should include the following statement with a numerical citation to the 
901  applicable Occupational Safety and Health Administration (OSHA) reference:117   
902   
903  DRUG-X is a hazardous drug.  Follow applicable special handling and disposal 
904  procedures.x  
905   
906  For radioactive products, this section should include instructions for avoiding radiation exposure 
907  of the patient and health care practitioners administering the drug (e.g., use effective shielding 
908  and waterproof gloves, use only under the direction of health care practitioners who are qualified 
909  by specific training and experience in the safe use and handling of radioactive materials).   
910   
 
114 See the draft guidance for industry Oral Drug Products Administered Via Enteral Feeding Tube: In Vitro Testing 
and Labeling Recommendations (June 2021).  When final, this guidance will represent the FDAs current thinking 
on this topic. 
 
115 Ibid. 
 
116 See Occupational Safety and Health Administrations website about hazardous drugs at 
https://www.osha.gov/hazardous-drugs. 
 
117 In this example, the x represents a numerical citation to the reference to OSHA Hazardous Drugs that should 
appear in the REFERENCES section.  See http://www.osha.gov/hazardous-drugs. 
 
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911  8.  Information on Drug Incompatibilities If the Drug Is Mixed In Vitro With Other 
912  Drugs  
913   
914  If the drug is mixed in vitro with other drugs, the DOSAGE AND ADMINISTRATION section 
915  must include essential information on drug incompatibilities118 and should include the 
916  explanation of the incompatibility.  For example: 
917   
918  2.x Drug Incompatibilities 
919  Avoid admixture of DRUG-X with calcium gluconate injection because ingredient-a in 
920  DRUG-X is unstable in the presence of calcium gluconate.  
921   
922  9.  Radiation Dosimetry 
923   
924  For radioactive drugs, the DOSAGE AND ADMINISTRATION section must include radiation 
925  dosimetry information (e.g., the estimated radiation absorbed for organs and tissues after drug 
926  administration) for health care practitioners administering the drug and the patient receiving the 
927  drug.119  FDA recommends that the radiation dosimetry information be presented at the end of 
928  this section under a subsection (i.e., the last subsection) entitled 2.x Radiation Dosimetry to 
929  improve accessibility of this information. 
930   
931  10.  Liposome Drug Products  
932   
933  See the guidance for industry Liposome Drug Products: Chemistry, Manufacturing, and 
934  Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation for 
935  recommended dosage- and administration-related information for liposome drug products in the 
936  DOSAGE AND ADMINISTRATION section.   
937   
938  M.  Storage Instructions for the Reconstituted or Diluted Product 
939   
940  The DOSAGE AND ADMINISTRATION section, as appropriate:120 
941   
942    Must contain storage conditions needed to maintain the stability of the reconstituted 
943  product, when important121 and should contain storage conditions needed to maintain the 
944  sterility of the reconstituted product  
945   
946    Should contain storage conditions needed to maintain the stability and sterility of the 
947  diluted product 
948   
 
118  21 CFR 201.57(c)(3)(iv). 
 
119 21 CFR 201.57(c)(3)(iii). 
 
120 Typically, storage instructions for the reconstituted or diluted product are included with the preparation 
instructions in the same subsection in the DOSAGE AND ADMINISTRATION section. 
 
121 21 CFR 201.57(c)(3)(iv). 
 
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949    Should include the duration for which the reconstituted or diluted product can be safely 
950  used under these storage conditions,122 and an appropriate discard statement 
951   
952  For example:123 
953   
954  2.x Storage Instructions for the Reconstituted Product 
955  If the DRUG-X reconstituted solution is not used immediately, store at controlled room 
956  temperature at 20C to 25C (68F to 77F) for up to 6 hours or refrigerate at 2C to 8C 
957  (36F to 46F) for no more than 24 hours.  Discard the unused DRUG-X reconstituted 
958  solution after 6 hours if stored at controlled room temperature or after 24 hours if 
959  refrigerated. 
960   
961  Information on storage conditions of the supplied drug (e.g., unopened package) (e.g., Keep the 
962  supplied vial in the outer carton to protect from light.) should not be included in the DOSAGE 
963  AND ADMINISTRATION section.124   
964   
965   
966  V.  ADDITIONAL RECOMMENDATIONS  
967   
968  A.  Abbreviations and Symbols  
969   
970  Applicants should consider whether abbreviations and symbols used in the DOSAGE AND 
971  ADMINISTRATION section could create the potential for medication errors, and if so, avoid 
972  their use.125  For example, the abbreviation QD should be avoided because it has been misread as 
973  QID; instead, it is preferable to use a phrase like once daily. 
974   
975  However, certain commonly used symbols (e.g., /, >, <, , ) may sometimes be preferable in 
976  this section when there is minimal risk of medication errors and where the replacement of 
977  symbols by lengthier, spelled-out words would make the presented information more difficult to 
978  read or understand.  For example, applicants should consider stating the following: 
979   
980    ALT > 3 times upper limit of normal (ULN) to  5 times ULN (instead of ALT 
981  greater than 3 times upper limit of normal (ULN) to less than or equal to ALT 5 times 
982  ULN) 
983   
 
122 USP General Chapter <7>. 
 
123 If the specific temperature ranges have already been described in the DOSAGE AND ADMINISTRATION 
section (e.g., for controlled room temperature), it is not necessary to repeat the specific temperature ranges in this 
subsection. 
 
124 The HOW SUPPLIED/STORAGE AND HANDLING section of labeling must include, as appropriate, storage 
conditions of the supplied drug (e.g., unopened package).  21 CFR 201.57(c)(17)(iv). 
 
125 Refer to the Institute for Safe Medication Practices list of error-prone abbreviations, symbols, and dose 
designations at https://www.ismp.org/recommendations/error-prone-abbreviations-list. 
 
  31  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
984    Estimated glomerular filtration rate of 30 mL/minute to 50 mL/minute (instead of 
985  estimated glomerular filtration rate of 30 mL per minute to 50 mL per minute) 
986   
987    5 mg/kg/day (instead of 5 mg per kg per day) 
988   
989  Additionally, certain widely understood abbreviations that are not associated with medication 
990  errors need not be defined in this section (e.g., mg, kg, mL). 
991   
992  B.  Metric System  
993   
994  FDA recommends using the metric system for dosage instead of the British Imperial System 
995  (e.g., use kg instead of lbs, and use mL instead of tsp).  FDA recommends that the DOSAGE 
996  AND ADMINISTRATION section not state the dosage in both the metric system and the British 
997  Imperial System because presenting both units of measure (e.g., kg and pounds) has contributed 
998  to medication errors.126  
999   
1000  C.  USP Descriptor 
1001   
1002  For drug products regulated under NDAs and ANDAs that are recognized in USP, the descriptor 
1003  USP should not be used next to the established name of the drug product in the DOSAGE AND 
1004  ADMINISTRATION section to avoid cluttering the required and recommended information in 
1005  this section.127   
 
126 Ibid. 
 
127 However, if an applicant wants to use the USP descriptor next to the established name of such a drug product in 
labeling, FDA recommends that it appear as such in the DOSAGE FORMS AND STRENGTHS, DESCRIPTION, 
and/or HOW SUPPLIED/STORAGE AND HANDLING sections. 
  32