Labeling for 

Combined Hormonal 

Contraceptives 

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DRAFT GUIDANCE
 
 
 
  This guidance document is being distributed for comment purposes only.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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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 Jennifer Dao at 301-796-8189.  
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER)
  
 
December 2017 

Labeling 

 
15419dft.doc  
12/14/17    
Labeling for 

Combined Hormonal 

Contraceptives 

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/GuidanceComplianceRegulatoryInformation/Guidances/default.htm  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER)
  
 
December 2017 

Labeling 

   
TABLE OF CONTENTS  
 
I.   INTRODUCTION............................................................................................................. 1
  
II.   BACKGROUND ............................................................................................................... 2
  
III.   LABELING RECOMMENDATIONS............................................................................ 2 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
Labeling for Combined Hormonal Contraceptives  
1 
Guidance for Industry1  
2 
3   
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7  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 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   
16  I.  INTRODUCTION 
17   
18  This guidance provides recommendations on information that should be included in the 
19  prescribing information for combined hormonal contraceptives (CHCs) that contain estrogen and 
20  progestin. CHCs include combined oral contraceptives (COCs), as well as non-oral products 
21  such as transdermal systems and vaginal rings. Many of the labeling recommendations in this 
22  guidance represent class labeling that should be included in all CHC prescribing information.  
23  General advice is provided [within brackets in bold font] where modifications of the prescribing 
24  information for specific products are needed.  
25   
26  This guidance follows the content and format requirements of the final rule Requirements on 
27  Content and Format of Labeling for Human Prescription Drug and Biological Products, issued 
28  in 2006, that amended human prescription and biological product labeling (commonly referred to 
29  as the physician labeling rule (PLR)),2,3 as well as the final rule Content and Format of Labeling 
30  for Human Prescription Drug and Biological Products; Requirements for Pregnancy and 
                                                 
1 This  guidance has been  prepared by the Division of Bone, Reproductive,  and Urologic Products in the Center for 
Drug Evaluation and Research at the Food and Drug Administration.  
 
2 21 CFR  201.56 and 201.57;  final rule Requirements on Content and Format of Labeling  for Human Prescription 
Drug and Biological Products (71 FR 3922, January 24, 2006); 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/LawsActsandRules/ucm084159.htm 
 
3 See the guidance for industry Labeling for Human Prescription Drug and  Biological Products  Implementing the 
PLR Content and Format Requirements. We  update guidances periodically.  To make sure you have the most recent 
version of a guidance, check the FDA Drugs guidance web page at  
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.  
 
  1
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
31  Lactation Labeling (commonly referred to as the pregnancy and lactation labeling rule (PLLR)) 
32  that was issued in 2014, which amended the 2006 PLR regulations.4,5    
33   
34  This guidance does not address the content of patient labeling, which is required for COCs under 
35  21 CFR 310.501. Applicants are advised to consider 21 CFR 310.501 and recently approved 
36  patient labeling for other contraceptive products when developing patient labeling for their 
37  products. 
38   
39  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
40  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
41  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
42  the word should in Agency guidances means that something is suggested or recommended, but 
43  not required. 
44   
45   
46  II.  BACKGROUND 
47   
48  The content and format requirements of the PLR and the PLLR (21 CFR 201.56 and 201.57) 
49  required revisions to CHC labeling under certain circumstances. In addition, the labeling for 
50  recently approved CHCs is consistent with the labeling requirements set forth in the PLR and the 
51  PLLR. This newer CHC labeling may be different from the labeling for some older CHC 
52  products. The updates to this guidance set forth labeling recommendations that represent newer 
53  class labeling that should be included in all CHC prescribing information consistent with the 
54  labeling requirements set forth in the PLR and PLLR (21 CFR 201.56 and 201.57).  We note that 
55  the specific advice provided in this guidance is not intended to cover every aspect of the PLR 
56  and PLLR requirements for CHC labeling.  Accordingly, we refer the reader to 21 CFR 201.56 
57  and 201.57, which set forth the PLR and PLLR content and format labeling requirements.  We  
58  also refer the reader to the PLR Requirements for Prescribing Information web page, which lists 
59  additional guidances that address specific requirements under PLR and PLLR.6    
60   
61   
62  III.  LABELING RECOMMENDATIONS 
63   
64  This section provides FDA recommendations for CHC labeling other than patient labeling.  
65  Because all CHCs contain an estrogen and a progestin, FDA believes that class labeling based on 
66  information known about estrogens/progestins generally is appropriate for many sections of 
67  CHC labeling. This section provides the recommended class labeling statements.  However, 
                                                 
4 21 CFR  201.56 and 201.57(c)(9);  final  rule  Content and Format of Labeling for Human Prescription Drug and 
Biological Products; Requirements for Pregnancy and Lactation Labeling (79 FR 72064, December 4, 2014); 
https://federalregister.gov/a/2014-28241 
 
5 See the draft guidance for industry Pregnancy, Lactation, and Reproductive Potential:  Labeling for Human 
Prescription  Drug and Biological Products  Content and Format. When  final, this guidance will represent the 
FDAs current  thinking on this topic.    
 
6 https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/LawsActsandRules/ucm084159.htm 
  2
  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
68  there are sections in labeling that should contain product-specific information (e.g., data on the 
69  efficacy outcome or bleeding profile demonstrated in clinical trials of the specific product, or 
70  results of a drug-drug interaction study conducted with a particular CHC product).  These 
71  labeling sections are identified in this section, and general guidance is provided as to the type of 
72  information that should be included. 
73   
74  For the Highlights of Prescribing Information, recommendations for product-specific text are 
75  listed in the appropriate footnotes directly below the labeling example.  Where labeling sections 
76  are listed without any recommended language, the reader is encouraged to review approved CHC 
77  labeling in the PLR format for guidance. 
78   
HIGHLIGHTS OF PRESCRIBING INFORMATION   ------------------------WARNINGS AND PRECAUTIONS--------------- 
These highlights do not include all the information needed to use   	  Vascular risks:  Stop if a thrombotic or thromboembolic event 
[DRUG NAME] safely and effectively.  See full prescribing  occurs.  Stop at least 4 weeks before and through 2 weeks after  
information for [DRUG NAME].      major surgery.  Start no earlier than 4 weeks after delivery, in 
  females who are not breast-feeding.   Consider cardiovascular risk 
[NAME (established name of progestin component, followed by  factors before initiating in all females, particularly  those over 35 
established name  of estrogen component)] tablets, for oral use[1]   years. (5.1, 5.4) 
Initial U.S. Approval: [YEAR][2]     	  Liver disease:  Discontinue if jaundice occurs.  (5.2) 
   	  Hypertension.   If used in females with well-controlled hypertension,  
WARNING: CIGARETTE SMOKING AND SERIOUS  monitor blood pressure and stop use if blood pressure rises 
CARDIOVASCULAR EVENTS   significantly. (5.3)  
See full prescribing information for complete boxed warning.    	  Gallbladder disease:  May cause or  worsen gallbladder disease.  
 	  [NAME]  is contraindicated in women over 35 years old who  (5.5) 
smoke. (4)   	  Adverse carbohydrate and lipid effect:  Monitor glucose in 
 	  Cigarette smoking increases the risk of serious cardiovascular  prediabetic and diabetic females using [NAME].  Consider an 
events from combination hormonal contraceptive (CHC)  use.   alternate contraceptive method for females with uncontrolled 
(5.1)[3]   dyslipidemia. (5.6) 
 	  Headache. Evaluate significant change in headaches and 
----------------------RECENT MAJOR CHANGES[4]---------------------  discontinue if indicated. (5.7) 
     Uterine bleeding:  May cause irregular bleeding or amenorrhea.   
Evaluate for other  causes if symptoms persist. (5.8)   
----------------------INDICATIONS AND USAGE------------------------ 
[NAME] is a progestin/estrogen [text][5] indicated for use by females      
of reproductive potential to prevent pregnancy. (1)[6],[7]    ----------------------ADVERSE REACTIONS------------------------------ 
  Most common adverse reactions reported in clinical trials ( x%)[11]  
are:  [text].[12] (6.1)   
----------------------DOSAGE AND  ADMINISTRATION-------------- 
 
 	  One tablet by mouth at the same time every day in the order  
directed on the blister pack.[8] (2.1)[9]   To report SUSPECTED ADVERSE REACTIONS,  contact 
(MANUFACTURER) at [text][13] or FDA at 1-800-FDA-1088 or 
 
www.fda.gov/medwatch.  
-----------------------DOSAGE FORMS AND STRENGTHS------------ 
 
 
-----------------------DRUG INTERACTIONS------------------------------ 
-----------------------CONTRAINDICATIONS----------------------------- 
Enzyme inducers (e.g., CYP3A4):  May decrease the effectiveness of  
   High risk of arterial or venous thrombotic diseases (4) 

[NAME] or increase breakthrough bleeding.  Counsel patients to use a 
   Breast cancer or other estrogen- or progestin-sensitive cancer (4) 

back-up or alternative method of contraception when enzyme inducers 
   Liver tumors, acute viral hepatitis or decompensated cirrhosis (4) 

are used with [NAME]. (7.1)  
   Undiagnosed abnormal uterine bleeding (4) 
 
 
   Pregnancy (4, 8.1) 

-----------------------USE IN SPECIFIC POPULATIONS--------------- 
   Hypersensitivity reactions to components of [NAME][10] (4) 
     Pregnancy:   Discontinue if pregnancy occurs. (8.1) 
 
   Lactation:  Advise use of another  method; [NAME] can decrease 
  milk production. (8.2)  
 
See 17 for PATIENT COUNSELING INFORMATION and FDA-
approved patient labeling. 
 
        Revised: [month/ye ar]  
79  [1] Should be modified as appropriate for non-oral formulations.  
80  [2] The year of the first approval of the combination of hormones should be inserted. 
  
81  [3] For oral hormonal contraceptives, it is acceptable to use the term  combination oral contraceptives (COCs) in place of CHCs.
  
82  [4] If applicable 

83  [5] COC or CHC 

84  [6] If other indications are approved, they should be provided in bullet form in the same order as in the Full Prescribing Information.  

85 
Recommended language for specific secondary indications is provided as follows:  
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  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
86 
[Acne:  Treat moderate acne in females who choose to use a combined hormonal contraceptive for contraception. (1.x)  
87 
Folate supplementation:  Raise folate levels in females who choose to use a combined hormonal contraceptive for contraception. (1.x)  
88 
Premenstrual Dysphoric Disorder (PMDD):  Treat symptoms of PMDD for females who choose to use a combined hormonal 
89 
contraceptive for contraception. (1.x)] 
90 
In the case of multiple indications, the format should be:  

91  [NAME] is a progestin/estrogen [text][5] indicated for  use by females  of reproductive potential to: 

92 
   [then list each indication as a separate bullet, beginning with prevent pregnancy] 
93  [7] If there were entry  criteria in the clinical trials that excluded females above a certain weight or body  mass index (BMI), the following language 

94 
should be added: 

95 
[Limitation of Use:  The efficacy in females with a [weight/BMI above x] has not been evaluated.]
  
96  [8] This should be revised as needed if a different dispenser is used. 

97  [9] For COCs, a bulleted format should be used to summarize if different pills are taken at different times during the cycle.  It should be noted if 

98 
the product must be taken with water  or with respect to meals.  This section should be  modified as appropriate for non-oral formulations.  Day 1 

99 
or Sunday start should be described as appropriate for  clarity.
  
100  [10] Only if evidence of hypersensitivity reactions exists, not if hypothetical concern. 
101  [11] The rate used as the cutoff for reporting should be specified.  
102  [12] All at or above the frequency cutoff should be specified, with terms likely to represent the same phenomenon grouped, and listed in 
103 
descending order of frequency.  Frequency  for individual terms should not be provided.  If approved for multiple  indications, applicants should 
104 
discuss with FDA whether to provide separate lists or to pool the adverse reaction data. 
105  [13] The manufacturers phone number should be inserted.  
106   
FULL PRESCRIBING INFORMATION: CONTENTS*  8   USE IN SPECIFIC POPULATIONS 
  8.1  Pregnancy 
WARNING:  CIGARETTE SMOKING AND SERIOUS  8.2  Lactation 
CARDIOVASCULAR EVENTS   8.3  Females and Males of Reproductive Potential 
1   INDICATIONS AND USAGE   8.4  Pediatric Use 
2  DOSAGE AND ADMINISTRATION  8.5  Geriatric Use 
   2.1   How to Start and Take [NAME]  8.6  Hepatic Impairment 
   2.2    Dosing [NAME]  8.7  Renal Impairment 
         2.3     Missed Doses  8.8 Race/Ethnicity  
   2.4    Advice in Case of Gastrointestinal Disturbances  8.9  Body Mass Index (BMI)/Body  Weight 
3  DOSAGE FORMS AND STRENGTHS   10  OVERDOSAGE  
4  CONTRAINDICATIONS   11  DESCRIPTION  
5  WARNINGS AND PRECAUTIONS  12  CLINICAL PHARMACOLOGY  
5.1  Thromboembolic Disorders and Other Vascular Conditions   12.1   Mechanism of Action  
5.2  Liver  Disease  12.2  Pharmacodynamics 
5.3  Hypertension  12.3  Pharmacokinetics  
5.4    Age-related Considerations   13  NONCLINICAL TOXICOLOGY 
5.5  Gallbladder  Disease     13.1   Carcinogenesis, Mutagenesis, Impairment of Fertility 
5.6  Adverse Carbohydrate and Lipid Metabolic Effects    13.2   Animal Toxicology and/or Pharmacology  
5.7   Headache   14  CLINICAL STUDIES 
5.8   Bleeding Irregularities and Amenorrhea  15  REFERENCES  
5.9    Depression  16  HOW SUPPLIED/STORAGE AND HANDLING  
5.10 Cervical Cancer   17   PATIENT COUNSELING INFORMATION 
5.11  Effect on Binding Globulins   
    5.12  Hereditary  Angioedema   *Sections or subsections omitted from  the full prescribing information 
5.13  Chloasma   are not listed.  
6  ADVERSE REACTIONS  
6.1 Clinical Trials Experience 
6.2 Postmarketing Experience  
7  DRUG  INTERACTIONS  
7.1  Effects of Other Drugs on Combined Hormonal 
Contraceptives 
7.2 Effects of Combined Hormonal Contraceptives on Other 
Drugs  
7.3  Effect on Laboratory  Tests  
 
107   
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108  WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS  
109   
110  Cigarette smoking increases the risk of serious cardiovascular events from combined 
111  hormonal contraceptive (CHC) use.  This risk increases with age, particularly in women 
112  over 35 years of age, and with the number of cigarettes smoked.  For this reason, CHCs, 
113  including [NAME], are contraindicated in women who are over 35 years of age and smoke.   
114  [See Contraindications (4) and Warnings and Precautions (5.1).]  
115   
116   
117  1 INDICATIONS AND USAGE 
118  [NAME] is indicated for use by females of reproductive potential to prevent pregnancy. 
119   
120  [Any important limitations of use should be added under the header Limitations of Use:.  If 
121  there were entry criteria in the clinical trials that excluded females above a certain weight or 
122  BMI, the following language should be added: Limitation of Use:  The efficacy in females with 
123  a [weight/BMI above x]  has not been evaluated.]  
124   
125  [If the product has multiple indications, the section should be formatted using subsections (e.g., 
126  1.1, 1.2).  Recommended language for specific secondary indications is provided below; 
127  however, the proposed language can be discussed  with the division if refinement is needed 
128  based on the specific clinical trials conducted in support of the secondary indication: 
129   
130  Acne: [NAME] is indicated for the treatment of moderate acne vulgaris in females who choose to use 
131  a combined hormonal contraceptive as their method of contraception.   
132   
133  Premenstrual Dysphoric Disorder (PMDD):  [NAME] is indicated for the treatment of symptoms of 
134  PMDD in females who choose to use a combined hormonal contraceptive as their method of 
135  contraception. The effectiveness of [NAME]  when used for more than [the duration of clinical 
136  trial(s) for this indication should be inserted] has not been evaluated.  Limitation of use:  [NAME]  
137  is not indicated for treatment of premenstrual syndrome (PMS).]  
138   
139  2 DOSAGE AND ADMINISTRATION 
140   
141  2.1  How to Start and Take [NAME]   
142  [Should be modified as warranted for non-oral formulations.] 
143   
144  [Information on Day 1 and/or Sunday start should be included, according to the method used in 
145  the registration trials.  A template for providing this information with respect to COCs in 
146  tabular form is provided in Table 1. The table should be modified as necessary to reflect dosing 
147  instructions in the registration trials (e.g., if dosing with respect to meals or fed/fasted was 
148  required). Additional text may be needed to describe different dosing regimens, such as a 
149  multiphasic dosing regimen.  Guidance on how to initiate use after pregnancy or childbirth 
150  should be provided (addressing use in lactating females); the general recommendation is not to 
151  start CHCs until 4 weeks postpartum.  Guidance should also be provided about switching from  
152  a different method, including a different COC, a transdermal system, vaginal ring, or a 
153  progestin-only method; instructions provided in Table 1 should be modified if warranted for 
154  the specific product.]  
155   
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156  Table 1. Instructions for Administration 
Starting [NAME] in females with no current  Day 1 start 
use of hormonal contraception     Take first tablet without regard to 
  meals on the first day  of menses  
[Instructions for Day 1 start or Sunday start     Take subsequent tablets once daily at 
based on the method(s) used in the registration  the same time each day 
clinical trial(s) should be included.]      Begin each subsequent pack on the 
same day of the week as the first cycle 
pack (i.e., on the day after taking the 
last tablet)  
Sunday start  
   Take first tablet without regard to 
meals on the first Sunday after the 
onset of menstrual period  
   Take subsequent tablets once daily at 
the same time each day 
   Use additional nonhormonal 
contraception for the first seven days  
of product use 
   Begin each subsequent pack on the 
same day of the week as the first cycle 
pack (i.e., on the day after taking the 
last tablet)  
Switching from another contraceptive  Start [NAME]:  
method  
   A COC      On the day when the new pack of the 
previous COC would have been started 
   Transdermal patch     On the day when next application 
would have been scheduled 
   Vaginal ring     On the day when next insertion would 
have been scheduled  
   Injection      On the day when next injection would 
have been scheduled  
   Intrauterine contraceptive     On the day of removal 
   Implant      On the day of removal 
157   
158  2.2 Dosing [NAME]   
159  [Should be modified as warranted for non-oral formulations.] 
160  Instruct patients to take one tablet by mouth at the same time every day.  To achieve maximum 
161  contraceptive effectiveness, patients must take [NAME] as directed, in the order directed on the 
162  blister pack [should be revised as needed if a different dispenser is used]. The failure rate may 
163  increase when pills are missed or taken incorrectly. [Should  be revised as appropriate for non-oral  
164  CHCs.]  
165   
166  [If relevant, it should be noted if the product must be taken with water or with respect to 
167  meals.]  
168   
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169  2.3 Missed Doses   
170  [Should be modified as warranted for non-oral formulations.] 
171  Instruct patients about the handling of missed doses (e.g., to take single missed pills as soon as 
172  possible) and to follow the dosing instructions provided in the FDA-approved patient labeling.  
173   
174  [Specific instructions should be provided about handling of missed doses and the need for back-
175  up contraception. A tabular display such as that shown in Table 2 can be helpful, but the 
176  specific recommendations should be based on instructions used in the clinical trial(s).]   
177   
178  Table 2. Instructions for Missed [NAME] Tablets  
   If one active tablet is missed in Weeks 1, 2,  Take the tablet as soon as possible. Continue 
or 3   taking one tablet a day until the pack is 
finished. 
   If two active tablets are missed in Week 1  Take the two missed tablets as soon as possible 
or Week 2   and the next two active tablets the next day.   
Continue taking one tablet a day  until the pack 
is finished. Additional nonhormonal 
contraception (such as condoms and 
spermicide) should be used as back-up if the 
patient has sex within 7 days after missing 
tablets.  
   If two active tablets are missed in the third  Day 1 start:  Throw out the rest of the pack and 
week or three or more active tablets are  start a new pack that same  day.  
missed in a row in Weeks 1, 2, or 3  
Sunday start:  Continue taking one tablet a day  
until Sunday, then throw out the rest of the 
pack and start a new pack that same day.   
Additional nonhormonal contraception 
(such as condoms and spermicide) should be 
used as back-up if the patient has sex within 
7 days after missing tablets.  
179   
180  2.4 Advice in Case of Gastrointestinal Disturbances   
181  [This section is for COCs only.] 
182  [In general, guidance provided here should reflect instructions given to subjects in the clinical 
183  trial(s).] 
184  If vomiting occurs within [X] hours after taking [NAME] [this can be individualized if the 
185  products pharmacokinetic profile indicates faster or slower absorption], the patient should 
186  proceed as if she missed a tablet.  In case of prolonged vomiting or diarrhea, [if no trial 
187  instructions were provided in the case of prolonged vomiting or diarrhea (greater than 48 hours), 
188  applicants should consider referring the reader to the CDC Selected Practice Recommendations 
189  web page (http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6205a1.htm#Fig5)].  
190   
191  3  DOSAGE FORMS AND STRENGTHS 
192  [The dosage of the progestin component should be described in milligrams and the estrogen 
193  component described in micrograms.] 
194   
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195  4 CONTRAINDICATIONS 
196  [NAME] is contraindicated in females who are known to have the following conditions:  
197     A high risk of arterial or venous thrombotic diseases.  Examples include females who are 
198  known to: 
199    Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1)]   
200    Have current or history of deep vein thrombosis or pulmonary embolism  [see Warnings 
201  and Precautions (5.1)]  
202    Have cerebrovascular disease [see Warnings and Precautions (5.1)]  
203    Have coronary artery disease [see Warnings and Precautions (5.1)]  
204    Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, 
205  subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings 
206  and Precautions (5.1)]  
207    Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1)]  
208    Have uncontrolled hypertension or hypertension with vascular disease [see Warnings and 
209  Precautions (5.3)]  
210    Have diabetes mellitus and are over age 35, diabetes mellitus with hypertension or 
211  vascular disease or other end-organ damage, or diabetes mellitus of > 20 years duration 
212  [see Warnings and Precautions (5.6)]  
213    Have headaches with focal neurological symptoms, migraine headaches with aura, or  
214  over age 35 with any migraine headaches [see Warnings and Precautions (5.8)]  
215     Current or history of breast cancer or other estrogen- or progestin-sensitive cancer   
216     Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and 
217  Precautions (5.2)]  
218     Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.9)]  
219     Pregnancy, because there is no reason to use CHCs during pregnancy [see Use in Specific 
220  Populations (8.1)]  
221     Hypersensitivity to any components of [NAME].  [Only if evidence of hypersensitivity 
222  reactions exists, not if hypothetical concern; if this bullet is used, a statement should be added:  
223  Observed reactions include...]  
224   
225  5  WARNINGS AND PRECAUTIONS 
226   
227  5.1 Thromboembolic Disorders and Other Vascular Conditions 
228     Stop [NAME] if an arterial or venous thrombotic/thromboembolic event occurs.   
229   
230     Stop [NAME] if there is unexplained loss of vision, proptosis, diplopia, papilledema, or 
231  retinal vascular lesions and evaluate for retinal vein thrombosis immediately.  
232   
233     Discontinue [NAME] during prolonged immobilization.  If feasible, stop [NAME] at least 
234  four weeks before and through two weeks after major surgery, or other surgeries known to 
235  have an elevated risk of thromboembolism.     
236   
237     Start [NAME] no earlier than four weeks after delivery in females who are not breast-
238  feeding. The risk of postpartum thromboembolism decreases after the third postpartum 
239  week, whereas the likelihood of ovulation increases after the third postpartum week.  
240   
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241     Before starting [NAME] evaluate any past medical history or family history of thrombotic or 
242  thromboembolic disorders and consider whether the history suggests an inherited or acquired 
243  hypercoagulopathy. [NAME] is contraindicated in females with a high risk of arterial or 
244  venous thrombotic/thromboembolic diseases [see Contraindications (4)]. 
245   
246  Arterial Events 
247  CHCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial 
248  infarction and stroke. The risk is greater among older women (> 35 years of age), smokers, and 
249  females with hypertension, dyslipidemia, diabetes, or obesity.    
250   
251  [NAME] is contraindicated in women over 35 years of age who smoke [see Contraindications 
252  (4)]. Cigarette smoking increases the risk of serious cardiovascular events from CHC use.  This 
253  risk increases with age, particularly in women over 35 years of age, and with the number of 
254  cigarettes smoked.  
255   
256  Venous Events   
257  Use of CHCs increases the risk of venous thromboembolic events (VTEs), such as deep vein 
258  thrombosis and pulmonary embolism.  Risk factors for VTEs include smoking, obesity, and family  
259  history of VTE, in addition to other factors that contraindicate use of CHCs [see Contraindications 
260  (4)]. While the increased risk of VTE associated with use of CHCs is well-established, the rates of 
261  VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1).  
262  The rate of VTE in females using COCs [or CHCs] has been estimated to be [the appropriate risk  
263  estimate should  be used depending on whether the product is  a COC  or a non-oral CHC; either  3 to 9 
264  cases per 10,000 woman-years for COCs or 3 to 12 cases per 10,000 women-years for non-oral 
265  CHCs].   
266   
267  The risk of VTE is highest during the first year of use of a COC and when restarting hormonal 
268  contraception after a break of four weeks or longer.  Based on results from a few studies, there is 
269  some evidence that this is true for non-oral products as well.  The risk of thromboembolic 
270  disease due to CHCs gradually disappears after CHC use is discontinued.  
271   
272  [The figure and text statement of risks of users should be modified as indicated for non-oral 
273  products. The rate range for CHCs (non-oral products) is 3 to 12; COC should be revised to 
274  CHC.] 
275   
276  Figure 1 shows the risk of developing a VTE for females who are not pregnant and do not use 
277  oral [or hormonal]  contraceptives, for females who use oral [or hormonal]  contraceptives, for 
278  pregnant females, and for females in the postpartum period.  To put the risk of developing a VTE 
279  into perspective: If 10,000 females who are not pregnant and do not use oral contraceptives are 
280  followed for one year, between 1 and 5 of these females will develop a VTE.  
281   
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282  Figure 1:  Likelihood of Developing a VTE 
283   
284   
285  [For extended cycle COCs, a statement should be provided if the annual hormonal exposure is 
286  greater than that with conventional monthly COCs that contain the same strength estrogen and 
287  progestin.] 
288   
289  Epidemiologic Studies Pertaining to [NAME] 
290  [If epidemiologic studies have evaluated [NAME] or progestin class, applicants should discuss with 
291  FDA whether and how the data  should be presented in labeling.]   
292    
293  5.2 Liver Disease 
294  Elevated Liver Enzymes  
295  [NAME] is contraindicated in females with acute viral hepatitis or severe (decompensated) 
296  cirrhosis of liver [see Contraindications (4)]. Discontinue [NAME] if jaundice develops.  Acute 
297  liver test abnormalities may necessitate the discontinuation of CHC use until the liver tests return  
298  to normal and CHC causation has been excluded.   
299   
300  Liver Tumors   
301  [NAME] is contraindicated in females with benign or malignant liver tumors [see 
302  Contraindications (4)]. CHCs increase the risk of hepatic adenomas.  An estimate of the 
303  attributable risk is 3.3 cases/100,000 CHC users.  Rupture of hepatic adenomas may cause death 
304  from abdominal hemorrhage.   
305   
306  Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (> 8 
307  years) CHC users.  The attributable risk of liver cancers in CHC users is  less than one case per 
308  million users. 
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309     
310  5.3 Hypertension 
311  [NAME] is contraindicated in females with uncontrolled hypertension or hypertension with vascular 
312  disease [see Contraindications (4)]. For all females, including those with well-controlled 
313  hypertension, monitor blood pressure at routine visits and stop [NAME] if blood pressure rises 
314  significantly. 
315   
316  An increase in blood pressure has been reported in females using CHCs, and this increase is more 
317  likely in  older women with extended duration of use.  The effect of CHCs on blood pressure may 
318  vary according to the progestin in the CHC.    
319   
320  5.4 Age-related Considerations 
321  The risk for cardiovascular disease and prevalence of risk factors for cardiovascular disease 
322  increase with age. Certain conditions, such as smoking and migraine headache without aura, that 
323  do not contraindicate CHC use in younger females, are contraindications to use in women over 
324  35 years of age [see Contraindications (4) and Warnings and Precautions (5.1)]. Consider the 
325  presence of underlying risk factors that may increase the risk of cardiovascular disease or VTE, 
326  particularly before initiating a CHC for women over 35 years, such as: 
327   
328     Hypertension 
329     Diabetes  
330     Dyslipidemia 
331     Obesity  
332   
333  5.5 Gallbladder Disease  
334  Studies suggest an increased risk of developing gallbladder disease among CHC users.  Use  of  
335  CHCs may also worsen existing gallbladder disease. 
336   
337  A past history of CHC-related cholestasis predicts an increased risk with subsequent CHC use.  
338  Females with a history of pregnancy-related cholestasis may be at an increased risk for CHC-
339  related cholestasis.  
340   
341  5.6 Adverse Carbohydrate and Lipid Metabolic Effects 
342  Hyperglycemia  
343  [NAME] is contraindicated in diabetic women over age 35, or females who have diabetes with 
344  hypertension, nephropathy, retinopathy, neuropathy, other vascular disease, or females with 
345  diabetes of > 20 years duration [see Contraindications (4)].   [NAME] may decrease glucose 
346  tolerance. Carefully monitor prediabetic and diabetic females who are using [NAME].  [Applicants 
347  should summarize here  if product-specific  information on  the effect  on carbohydrate metabolism is  
348  available.]  
349   
350  Dyslipidemia  
351  Consider alternative contraception for females with uncontrolled dyslipidemia.  [NAME] may cause 
352  adverse lipid changes.  [Applicants should summarize here if  product-specific information on the 
353  effect on lipids is available.]  
354   
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355  Females with hypertriglyceridemia, or a family history thereof, may have an increase in serum  
356  triglyceride concentrations when using [NAME], which may increase the risk of pancreatitis. 
357   
358  5.7 Headache 
359  [NAME] is contraindicated in females who have headaches with focal neurological symptoms or 
360  have migraine headaches with aura, and in women over age 35 years who have migraine 
361  headaches with or without aura [see Contraindications (4)]. 
362   
363  If a woman using [NAME] develops new headaches that are recurrent, persistent, or severe, 
364  evaluate the cause and discontinue [NAME] if indicated.  Consider discontinuation of [NAME] if  
365  there is an increased frequency or severity of migraines during CHC use  (which may be prodromal 
366  of a cerebrovascular event).  
367   
368  5.8 Bleeding Irregularities and Amenorrhea 
369  Unscheduled Bleeding and Spotting 
370  Females using [NAME] may experience unscheduled (breakthrough or intracyclic) bleeding and 
371  spotting, especially during the first three months of use.  Bleeding irregularities may resolve over 
372  time or by changing to a different contraceptive product.  If bleeding persists or occurs after 
373  previously regular cycles, evaluate for causes such as pregnancy or malignancy.  
374   
375  [The following sections should summarize  data from product-specific clinical  trials that describe  
376  the occurrence of unscheduled (breakthrough) bleeding, frequency of amenorrhea, and absence of 
377  scheduled (withdrawal) bleeding.  The frequency of discontinuation due to bleeding complaints 
378  should  be provided.  Suggested language is provided below.] 
379   
380  Based on subject diaries from  [number] clinical trial(s) of [NAME], [range of frequency, in percent 
381  of subjects, should be  given] of females experienced unscheduled bleeding per 28-day cycle [should 
382  be modified as appropriate  for extended cycle products]. A total of [number out of total sample size]  
383  subjects  [percent]  discontinued due to menstrual disorders including [Preferred Terms should be  
384  specified]. 
385   
386  Amenorrhea and Oligomenorrhea 
387  Females who use [NAME] may experience absence of scheduled (withdrawal) bleeding, even if  
388  they are not pregnant.  Based on subject diaries from clinical trials of [NAME] for up to [number]  
389  cycles, [percent]  of females experienced cycles with no scheduled bleeding.   
390   
391  If scheduled bleeding does not occur, consider the possibility of pregnancy.  If the patient has not 
392  adhered to the prescribed dosing schedule (missed one or two active tablets or started taking them  
393  on a day later than she should have [should  be  modified as needed  for  multiphasic regimens or non-
394  oral formulations]), consider the possibility of pregnancy at the time of the first missed period and 
395  perform appropriate diagnostic measures.  If the patient has adhered to the prescribed dosing 
396  schedule and misses two consecutive periods, rule out pregnancy.  [Should  be  modified as needed to  
397  account for extended cycle products and/or products with  a short half-life.]      
398   
399  After discontinuation of a CHC, amenorrhea or oligomenorrhea may occur, especially if these 
400  conditions were pre-existent. 
401   
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402  5.9 Depression 
403  Carefully observe females with a history of depression and discontinue [NAME] if depression 
404  recurs to a serious degree. Data  on  the  association of CHCs with onset of depression or 
405  exacerbation of existing depression are limited.   
406   
407  5.10 Cervical Cancer 
408  Some studies suggest that CHCs  are  associated  with an increase in the risk of cervical cancer or  
409  intraepithelial neoplasia.  There is controversy about the extent to which these findings are due to 
410  differences in sexual behavior and other factors.  
411   
412  5.11 Effect on Binding Globulins 
413  The estrogen component of [NAME] may raise the serum concentrations of thyroxine-binding 
414  globulin, sex hormone-binding globulin, and cortisol-binding globulin.  The dose of replacement  
415  thyroid hormone or cortisol therapy may need to be increased.   
416   
417  5.12 Hereditary Angioedema 
418  In females with hereditary angioedema, exogenous estrogens may induce or exacerbate 
419  symptoms of angioedema.  
420   
421  5.13 Chloasma 
422  Chloasma may occur with [NAME] use, especially in females with a history of chloasma  
423  gravidarum.  Advise females with a history of chloasma to avoid exposure to the sun or 
424  ultraviolet radiation while using [NAME].
425   
426  6 ADVERSE REACTIONS 
427  The following serious adverse reactions with the use of CHCs are discussed elsewhere in 
428  labeling: 
429   
430     Serious cardiovascular events [see Boxed Warning and Warnings and Precautions (5.1)]  
431     Vascular events [see Warnings and Precautions (5.1)]  
432     Liver disease [see Warnings and Precautions (5.2)]  
433   
434  6.1 Clinical Trials Experience 
435  Because clinical trials are conducted under widely varying conditions, adverse reaction rates 
436  observed in the clinical trials of one product cannot be directly compared to rates in the clinical 
437  trials of another product and may not reflect the rates observed in practice.  
438   
439  [Clinical trials experience: See the guidance for industry Adverse Reactions Section of Labeling 
440  for Human Prescription Drug and Biological Products  Content and Format for detailed 
441  instructions.  The following should be provided:  (1) common adverse reactions; (2) adverse 
442  reactions leading to study discontinuation; and (3) serious adverse reactions, in a text list or 
443  tables, sorted by decreasing order of frequency.  The frequency cutoff should be noted and 
444  should be appropriate for the safety database.  Terms that may represent the same 
445  phenomenon before calculating frequency (e.g., disorders of menstrual frequency/volume, 
446  nausea/vomiting) should be grouped.]  
447   
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448  6.2 Postmarketing Experience 
449  The following adverse reactions have been identified during postapproval use of [NAME].  
450  Because these reactions are reported voluntarily from a population of uncertain size, it is not 
451  always possible to reliably estimate their frequency or establish a causal relationship to product 
452  exposure. 
453   
454  [Postmarketing experience:  See the guidance for industry Adverse Reactions Section of Labeling 
455  for Human Prescription Drug and Biological Products  Content and Format for detailed 
456  instructions.  Typically, adverse reactions already  described elsewhere in labeling should not be 
457  repeated in subsection 6.2.  However, if a serious adverse reaction (such as a pulmonary 
458  embolus) is described in class labeling for CHCs and there are no such events that occurred in 
459  the clinical trial(s) of the product but such events have occurred in the postmarketing setting 
460  with the product, then those postmarketing events should be included here.]   
461   
462  7 DRUG INTERACTIONS 
463  The sections below provide information on substances for which data on drug interactions with 
464  CHCs are available.  There is little information available about the clinical effect of most drug 
465  interactions that may affect CHCs.  However, based on the known pharmacokinetic effects of 
466  these drugs, clinical strategies to minimize any potential adverse effect on contraceptive 
467  effectiveness or safety are suggested. 
468   
469  Consult the approved product labeling of all concurrently used drugs to obtain further 
470  information about interactions with CHCs or the potential for metabolic enzyme or transporter 
471  system alterations. 
472   
473  [If no studies were conducted with the product, this fact should be indicated as shown below; 
474  the general class labeling provided in the following sections should still be included.]  
475   
476  No drug-drug interaction studies were conducted with [NAME].  
477   
478  7.1 Effects of Other Drugs on Combined Hormonal Contraceptives  
479  Substances Decreasing the Plasma Concentrations of CHCs and Potentially Diminishing the 
480  Efficacy of CHCs: 
481   
482  Table 3 includes substances that demonstrated an important drug interaction with [NAME]. 
483   
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484  Table 3. Significant Drug Interactions Involving Substances That Affect CHCs 
Metabolic Enzyme Inducers 
   Concomitant use of CHCs with metabolic enzyme inducers 
may decrease the plasma concentrations of the estrogen and/or  
progestin component of CHCs [see Clinical Pharmacology 
(12.3)]. 
Clinical effect 
   Decreased exposure of the estrogen and/or progestin 
component of CHCs may potentially diminish the 
effectiveness of CHCs and may lead to contraceptive failure 
or an increase in breakthrough bleeding. 
   Counsel females to use an alternative method of contraception 
or a backup method when enzyme inducers are used with 
Prevention or management  CHCs.  
   Continue backup contraception for 28 days after discontinuing 
the enzyme inducer to maintain contraceptive reliability.  
 
Aprepitant, barbiturates, bosentan, carbamazepine, efavirenz,  
felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, 
Examples 
rifabutin, rufinamide, topiramate, products containing St. Johns 
wort,a and certain protease inhibitors (see separate section on 
protease inhibitors below). 
Colesevelam 
   Concomitant use of CHCs with colesevelam significantly 
decreases systemic exposure of ethinyl estradiol [see Clinical 
Pharmacology (12.3)]. 
Clinical effect     Decreased exposure of the estrogen component of CHCs may 
potentially reduce contraceptive efficacy or result in an 
increase in breakthrough bleeding, depending on the strength 
of ethinyl estradiol in the CHC. 
Prevention or management  Administer 4 or more hours apart to attenuate this drug interaction. 
485  a Induction  potency of  St. Johns wort may vary widely based  on preparation. 
486   
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487  Substances increasing the systemic exposure of CHCs:  
488  Co-administration of atorvastatin or rosuvastatin and CHCs containing ethinyl estradiol increase 
489  systemic exposure of ethinyl estradiol by approximately 20 to 25 percent.  Ascorbic acid and 
490  acetaminophen may increase systemic exposure of  ethinyl estradiol, possibly by inhibition of 
491  conjugation. CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit 
492  juice,7 or ketoconazole may increase systemic exposure of the estrogen and/or progestin 
493  component of CHCs.  
494   
495  Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) protease inhibitors and non-
496  nucleoside reverse transcriptase inhibitors:  
497  Significant decreases in systemic exposure of the estrogen and/or progestin have been noted 
498  when CHCs are co-administered with some HIV protease inhibitors (e.g., nelfinavir, ritonavir, 
499  darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir), some  
500  HCV protease inhibitors (e.g., boceprevir and telaprevir), and some non-nucleoside reverse 
501  transcriptase inhibitors (e.g., nevirapine).  
502   
503  In contrast, significant increases in systemic exposure of the estrogen and/or progestin have been 
504  noted when CHCs are co-administered with certain other HIV protease inhibitors (e.g., indinavir 
505  and atazanavir/ritonavir) and with other non-nucleoside reverse transcriptase inhibitors (e.g., 
506  etravirine).  
507   
508  7.2 Effects of Combined Hormonal Contraceptives on Other Drugs  
509  Table 4 provides significant drug interaction information for drugs co-administered with 
510  [NAME].  
511   
                                                 
7  The effect  of  grapefruit juice varies widely among brands  and is concentration-, dose-, and preparation-dependent.   
Studies have shown that it could be classified as a strong CYP3A inhibitor when a certain preparation was used  
(e.g., high dose, double-strength) or as a moderate CYP3A  inhibitor when another preparation was used (e.g., low 
dose, single strength).  
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512  Table 4. Significant Drug Interaction Information for Drugs Co-Administered With CHCs 
Lamotrigine 
   Concomitant use of CHCs with lamotrigine may significantly 
decrease systemic exposure of lamotrigine due to induction of 
lamotrigine glucuronidation [see Clinical Pharmacology 
Clinical effect  
(12.3)]. 
   Decreased systemic exposure of lamotrigine may reduce 
seizure control. 
Dose adjustment may be necessary.  Consult the approved product 
Prevention or management 
labeling for lamotrigine.  
Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy  
Concomitant use of CHCs with thyroid hormone replacement 
therapy or corticosteroid replacement therapy may increase 
Clinical effect  
systemic exposure of thyroid-binding and cortisol-binding 
globulin [see Warnings and Precautions (5.11)]. 
The dose of replacement thyroid hormone or cortisol therapy may 
Prevention or management  need to be increased. Consult the approved product labeling for 
the therapy in use.  [See Warnings and Precautions (5.11)]. 
Other Drugs  
Concomitant use of CHCs may decrease systemic exposure of 
acetaminophen, morphine, salicylic acid, and temazepam.  
Clinical effect  Concomitant use with ethinyl estradiol-containing CHCs may 
increase systemic exposure of other drugs (e.g., cyclosporine, 
prednisolone, theophylline, tizanidine, and voriconazole). 
The dosage of drugs that can be affected by this interaction may 
Prevention or management  need to be increased. Consult the approved product labeling for 
the concomitantly used drug. 
513   
514  [If available, specific clinical pharmacology data should be added here concerning the effects of 
515  the product on human CYP enzymes at clinically relevant concentrations (see Clinical 
516  Pharmacology (12.3)).]  
517   
518  7.3 Effect on Laboratory Tests 
519  The use of CHCs may influence the results of certain laboratory tests, such as coagulation 
520  factors, lipids, glucose tolerance, and binding proteins. 
521   
522  8  USE IN SPECIFIC POPULATIONS 
523  [Certain subsections and headings described in the PLLR may not be pertinent to the labeling 
524  for CHCs.  For example, it is not anticipated that this section would include a description of a 
525  pregnancy registry or would have information included under the Clinical Considerations 
526  heading. When information is clearly not applicable, such headings and subsections are  
527  omitted. See 21 CFR 201.56, 201.57(c)(9)(i)-(iii), and the draft guidance for industry Pregnancy, 
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528  Lactation, and Reproductive Potential:  Labeling for Human Prescription Drug and Biological 
529  Products  Content and Format for complete details on content for PLLR labeling.]  
530   
531  8.1 Pregnancy 
532   
533  Risk Summary 
534  [This section should summarize the human, animal, and pharmacologic data and identify  the 
535  source of the data.  If the product contains  a new progestin or estrogen,  applicants should provide  
536  a risk  statement(s)  that  describes, for the drug,  the  risk of adverse  developmental outcomes  based  
537  on all relevant human data, animal data, and the drugs pharmacology.  If  there are no human 
538  data, then a statement that there are no human data must be made in the Risk Summary 
539  (21 CFR 201.57(c)(9)(i)(B)) and the human data section should not be included. If  embryo/fetal  
540  studies were conducted,  then  a  sentence summarizing those studies should  be included  here with  
541  details under Animal Data.  If no studies were done, then  a statement should  be made in the Risk 
542  summary and the animal data section should not  be included.  
543   
544  If the product contains a  well-characterized progestin and  estrogen, the class language provided  
545  below should be used.]  
546   
547  [NAME]  is  contraindicated  in  pregnancy because there is no reason to use CHCs in pregnancy.   
548  Discontinue  [NAME]  if  pregnancy  occurs.   Epidemiologic studies and meta-analyses have not 
549  found an increased risk of genital or nongenital birth defects (including cardiac anomalies and 
550  limb-reduction defects) following exposure to CHCs before conception or during early 
551  pregnancy.   In animal reproduction studies in  [species], [results should be summarized]. [OR]  
552  Animal studies to evaluate embryo/fetal toxicity were not conducted. 
553   
554  In the U.S. general population, the estimated background risk of major birth defects and miscarriage 
555  in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively. 
556   
557  Data  
558  Human Data  
559  [Applicants should describe the data regarding adverse developmental outcomes, adverse 
560  reactions, and other adverse effects, including information about the data source, number of 
561  subjects, study duration, exposure time, and limitations of the data.] 
562   
563  Animal Data  
564  [Embryo/fetal (Segment II and III) studies should be  reported  here.  If no studies  were done, this  
565  heading should not be included.] 
566   
567  8.2 Lactation 
568   
569  Risk Summary 
570  Contraceptive hormones and/or metabolites are present in human milk.  [The concentration in 
571  human milk and the actual or estimated infant dose, if available, should be described, as well 
572  as the effects on the breast-fed infant.]  CHCs can reduce milk production in breast-feeding 
573  females.  This reduction can occur at any time but is less likely to occur once breast-feeding is well-
574  established. When possible, advise the nursing female to use other methods of contraception until 
575  she discontinues breast-feeding.  [See also Dosage and Administration (2.2).]   The developmental 
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576  and health benefits of breast-feeding should be considered along with the mothers clinical need 
577  for (name of drug) and any potential adverse effects on the breast-fed child from (name of drug) 
578  or from the underlying maternal condition.  
579    
580  Data  
581  [If available, specific pharmacologic data should be added here concerning the percentage of 
582  the product that is present in the breast milk of postpartum females.]    
583   
584  8.4 Pediatric Use 
585  Safety and efficacy of [NAME] have been established in females of reproductive potential.  
586  [Unique efficacy or safety information relevant to patients younger than 18 years of age should be 
587  provided here.]  Use of [NAME] before menarche is not indicated. 
588   
589  8.5 Geriatric Use 
590  [NAME] has not been studied in postmenopausal women and is not indicated in this population. 
591   
592  8.6 Hepatic Impairment 
593  [Contraindication and any other statements that are relevant to this heading should be included 
594  with appropriate cross-references [see Contraindications (4) and Warnings and Precautions 
595  (5.4)]. This section should be omitted if there are no relevant data.] 
596   
597  8.7 Renal Impairment   
598  [Any statements that are relevant to this heading should be added with appropriate cross-
599  references.  This section should be omitted if there are no relevant data.] 
600   
601  8.8 Race/Ethnicity 
602  [Any statements that are relevant to this heading should be added and cross-referenced to other 
603  sections if appropriate. This section should be omitted if there are no relevant data.] 
604   
605  8.9 Body Mass Index (BMI)/Body Weight 
606  [If studies limited eligibility on the basis of BMI/body weight:]  The safety and efficacy of 
607  [NAME] in females with a BMI or body weight > [exclusion criteria should be stated] have 
608  not been evaluated [see Clinical Studies (14)].  
609   
610  If data indicate an adverse effect on efficacy, that should be summarized here, and included 
611  under Limitations of Use in INDICATIONS AND USAGE and described in CLINICAL 
612  STUDIES.  This section should be omitted if there are no relevant data and BMI/body weight 
613  were not exclusionary in the clinical trials.]   
614   
615  10 OVERDOSAGE 
616  There have been no reports of serious adverse outcomes from overdose of CHCs, including 
617  ingestion by children. Overdose may cause uterine bleeding in females and nausea. 
618   
619  [If data are available, any pharmacokinetic or clinical statements that are relevant to this  
620  heading should be added; also, what should be monitored in case of overdose of the product 
621  should be stated.] 
622   
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623  11 DESCRIPTION 
624  [This section should include the proprietary name and established name, if any, of the 
625  CHC product, as well as key descriptors of the CHC product (e.g., the type of dosage 
626  form(s) and routes of administration).] 
627   
628  12 CLINICAL PHARMACOLOGY 
629   
630  12.1 Mechanism of Action 
631  CHCs prevent pregnancy primarily by suppressing ovulation.   
632   
633  [If studies establish additional mechanisms by which the drug prevents conception, the 
634  additional mechanisms should be described here.  Speculative claims of untested mechanisms of 
635  action should not be included. 
636   
637  Receptor-binding studies should not be added for the purpose of claims unless the claims were  
638  previously agreed upon with the division and are adequately supported with data from clinical 
639  studies.] 
640   
641  12.2 Pharmacodynamics 
642  [If there are no relevant pharmacodynamic data, this subsection must contain a statement 
643  indicating this lack of information (21 CFR 201.57(c)(13)(i)(B)).] 
644   
645  12.3 Pharmacokinetics 
646  [Available information should be provided to include the following subsections: 
647   
648     Absorption (including food effect)  
649     Distribution  
650     Elimination 
651    Metabolism 
652    Excretion  
653     Specific populations (e.g., geriatric patients, pediatric patients, racial or ethnic groups, 
654  patients with renal impairment, patients with hepatic impairment)  
655     Drug interaction studies] 
656   
657  13  NONCLINICAL TOXICOLOGY 
658   
659  13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 
660  [If applicable, nonclinical data should be summarized if human data are not available.]  
661   
662  13.2 Animal Toxicology and/or Pharmacology 
663  [If applicable, nonclinical data should be summarized if human data are not available.  
664  Embryo/fetal (Segment II and III) studies should be summarized in subsection 8.1] 
665   
666  14 CLINICAL STUDIES  
667  [Contraceptive efficacy should be reported in terms of the 1-year Pearl Index and 95 percent 
668  confidence interval around the point estimate.  If studies were conducted in different 
669  geographic regions, the U.S. Pearl Index should be the focus of this section. 
670   
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671  This information should be preceded by a description of the clinical trial efficacy database, 
672  including the overall exposure, demographics, trial design, and any exclusions from the clinical 
673  trial database beyond the contraindications to use of hormonal contraceptives.  If indications in 
674  addition to contraception are sought, presentation of those results should be discussed with 
675  FDA.  
676   
677  If available, information about return to fertility following discontinuation of the product 
678  should be provided here.] 
679    
680  15 REFERENCES 
681  [References should be minimized, but can include recommendations by an authoritative 
682  scientific body or a standardized methodology, scale, or technique if the labeling has to 
683  summarize or rely on this information for the safe and effective use of the CHC.  Also citations 
684  of studies (e.g., epidemiologic studies) that inform labeling about the specific product should be 
685  referenced.]   
686   
687  16 HOW SUPPLIED/STORAGE AND HANDLING  
688  [The United States Pharmacopeia storage temperature range, not a single storage temperature 
689  value, should be included.  Contraceptive products use different dispensers; more complicated 
690  dispensers should be described here.]  
691   
692  17 PATIENT COUNSELING INFORMATION  
693  [Although this provides general class counseling statements, these statements should be 
694  consistent with information provided in the preceding prescribing information.  Some 
695  statements, particularly regarding instructions for missed pills or when to rule out pregnancy, 
696  should be customized for the particular product.] 
697   
698  Advise the patient to read the FDA-approved patient labeling (Patient Information and 
699  Instructions for Use). 
700   
701  Cigarette Smoking 
702  Cigarette smoking increases the risk of serious cardiovascular events from CHC use.  
703  Women who are over 35 years old and smoke should not use [NAME] [see Boxed Warning 
704  and Warnings and Precautions (5.1)]. 
705   
706  Venous Thromboembolism 
707  The increased risk of VTE compared to non-users of CHCs is greatest after initially starting a 
708  CHC or restarting (following a 4-week or greater interruption in intake) the same or a 
709  different CHC [see Warnings and Precautions (5.1)]. 
710   
711  Use during Pregnancy 
712  [NAME] is not to be used during pregnancy. Instruct the patient to stop further intake of 
713  [NAME] if pregnancy is confirmed during treatment [see Contraindications (4)]. 
714   
715  Sexually Transmitted Infections  
716  [NAME] does not protect against HIV infection and other sexually transmitted infections.  
717   
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  Contains Nonbinding Recommendations 
Draft  Not for Implementation  
718  Dosing and Missed Pill Instructions 
719  Patients should take one tablet daily by mouth at the same time every day.  Advise patients 
720  about what to do in the event pills are missed.  See What to Do if You Miss Pills section 
721  in FDA-approved patient labeling [see Dosage and Administration (2.1)]. [Should be 
722  modified as warranted for non-oral formulations.]  
723   
724  Need for Additional Contraception  
725     Postpartum females who have not yet had a period when they start [NAME] need to 
726  use an additional method of contraception until [product-specific information about 
727  starting CHCs in postpartum females should be provided]  [see Dosage and 
728  Administration (2.2)]. 
729     There is a need for a back-up or alternative method of contraception when enzyme  
730  inducers are used with [NAME] [see Drug Interactions (7.1)].  
731   
732  Lactation  
733  [NAME] may reduce breast milk production.  This is less likely to occur if breast-feeding is 
734  well established.  When  possible,  nursing  women should use other methods of contraception 
735  until they have discontinued breast-feeding [see Use in Specific Populations (8.2)].   
736   
737  Amenorrhea and Possible Symptoms of Pregnancy 
738  Amenorrhea may occur.  Advise the patient to contact a health care provider in the event of 
739  amenorrhea in two or more consecutive cycles or in case of symptoms of pregnancy such as 
740  morning sickness or unusual breast tenderness.  [Should be modified as warranted for 
741  extended-cycle products.]  [See Warnings and Precautions (5.8).]  
742   
743  Fertility following Discontinuation of [NAME] 
744  Resumption of fertility after discontinuing [NAME] is expected.  [Product-specific 
745  information about the likely interval before fertility is restored should be provided, if 
746  available.]   [See Clinical Studies (14).] 
747   
748  [Other relevant information for prescribers to convey to patients to use the drug safely and 
749  effectively should be included.   
750   
751  Required manufacturer information (21 CFR 201.1 and 201.100(e) for drugs and 21 CFR part 
752  610, subpart G, for biological products) should be provided at the end of the prescribing 
753  information, as well as in the patient labeling (21 CFR 310.501(c)(13)(i)), unless the patient 
754  labeling is attached to the prescribing information.] 
755   
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