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Guidance for Industry

Labeling for Combined Oral 

Contraceptives

DRAFT GUIDANCE

This guidance document is being distributed for comment purposes only.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publication of the Federal Register notice announcing the availability of the draft guidance. 

Submit comments to the Division of Dockets Management (HFA-305), Food and Drug 

Administration, 5630 Fishers Lane, room 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 on the content of the draft document contact Margaret Kober, 301-827-4243.

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

March 2004

Labeling

Revision 1
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Guidance for Industry

Labeling for Combined Oral 

Contraceptives

Additional copies are available from:

Office of Training and Communication

Division of Drug Information (HFD-240)

Center for Drug Evaluation and Research (CDER)

Food and Drug Administration

5600 Fishers Lane

Rockville, MD 20857

(Tel) 301-827-4570

http://www.fda.gov/cder/guidance/index.htm

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

March 2004

Labeling

Revision 1
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TABLE OF CONTENTS

I. INTRODUCTION................................................................................................................. 1

II. LABELING FOR PACKAGE INSERT ............................................................................. 2

PROPRIETARY NAME (ESTABLISHED NAME)..................................................... 2

DESCRIPTION................................................................................................................. 2

CLINICAL PHARMACOLOGY.................................................................................... 2

INDICATIONS AND USAGE......................................................................................... 3

CONTRAINDICATIONS ................................................................................................ 4

WARNINGS...................................................................................................................... 4

PRECAUTIONS ............................................................................................................... 8

ADVERSE EXPERIENCES .......................................................................................... 10

POSSIBLE HEALTH BENEFITS ................................................................................ 11

OVERDOSAGE.............................................................................................................. 11

DOSAGE AND ADMINISTRATION........................................................................... 11

HOW SUPPLIED............................................................................................................ 12

STORAGE....................................................................................................................... 12

REFERENCES................................................................................................................ 12

III. PATIENT LABELING....................................................................................................... 13

WHAT IS (OC NAME)? ................................................................................................ 13

HOW WELL DOES (OC NAME) WORK?................................................................. 13

HOW DO I TAKE (OC NAME)?.................................................................................. 14

WHAT SHOULD I DO IF I MISS ANY PILLS? ........................................................ 15

WHO SHOULD NOT TAKE (OC NAME)?................................................................ 16

WHAT ELSE SHOULD I KNOW ABOUT TAKING (OC NAME)?....................... 16

WHAT ARE COMMON SIDE EFFECTS OF BIRTH CONTROL PILLS? .......... 17

WHAT ARE THE MOST SERIOUS RISKS OF TAKING BIRTH CONTROL 

PILLS? ............................................................................................................................. 18

DO BIRTH CONTROL PILLS CAUSE CANCER? .................................................. 19

WHAT IF I WANT TO BECOME PREGNANT? ...................................................... 19

ARE THERE OTHER BENEFITS OF THE BIRTH CONTROL PILL?................ 19
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1

Guidance for Industry12

3 Labeling for Combined Oral Contraceptives

4

5

6

7

8

9 This draft guidance, when finalized, will represent FDA's current thinking on this topic. It does not create 

10 or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an 

11 alternative approach if it satisfies the requirements of the applicable statutes and regulations. If you want 

12 to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If 

13 you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this 

14 guidance.

15

16

17

18

19

20

21

22

23

24 I. INTRODUCTION

25

26 This guidance describes the recommended labeling for health care providers and patient 

27 instructions for use for new drug applications (NDAs) and abbreviated new drug applications

28 (ANDAs) for combined oral contraceptives (OCs) that contain estrogen and progestin. A draft 

29 guidance on this topic was issued for comment in June 2000. Many comments were received on 

30 the 2000 draft guidance and, as a result, many changes have been made to the guidance. Because 

31 of the many changes, we are making the guidance available again in draft to allow for additional 

32 public review and input. The references listed at the end of this guidance do not go in the 

33 labeling.

34

35

36

 

1

 This guidance was developed by the Division of Reproductive and Urologic Drug Products in the Center for Drug 

Evaluation and Research (CDER), Food and Drug Administration (FDA). 
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37 II. LABELING FOR PACKAGE INSERT

38

39 We recommend the following labeling be used for combined oral contraceptives:

40 PROPRIETARY NAME (ESTABLISHED NAME)

41

42 Supplied by manufacturer

43 WARNING: CIGARETTE SMOKING

44

45 Combined oral contraceptives (OCs) are not recommended for women who are over 35 years old 

46 and smoke. Cigarette smoking increases the risk of serious cardiovascular side effects from OC 

47 use. The risk increases with age and with the number of cigarettes smoked.

48

49 This product does not protect against infection from HIV (the virus that causes AIDS) or 

50 other sexually transmitted diseases.

51

52 DESCRIPTION

53

54 Supplied by manufacturer

55

56 CLINICAL PHARMACOLOGY

57

58 Mode of action

59

60 OCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible 

61 mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial 

62 changes that reduce the likelihood of implantation.

63 Receptor binding studies can be summarized briefly here if clinically relevant.

64

65 Pharmacokinetics

66

67 Supplied by manufacturer, to include the following subsections:

68

69 • Absorption

70 • Distribution

71 • Metabolism

72 • Excretion

73 • Special Populations

74 • Renal and Hepatic Impairment

75 • Drug-drug Interactions (include mechanism for drug interaction for specific product, refer to 

76 PRECAUTIONS for class-labeling for OC products.)

77
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78 INDICATIONS AND USAGE

79

80 (Name of OC) is indicated for use by women to lower the risk of becoming pregnant.

81 Other approved indications appear here.

82 Pregnancy rates from clinical trials should be placed here.

83 In clinical trials of (insert name of OC here), about (insert whole number here) out of 100 

84 women became pregnant during the first year of use. The effectiveness of any OC depends on 

85 correct and consistent use, and factors that affect ability to conceive, including age and frequency 

86 of intercourse. 

87

88 The following table shows estimates of the number of women who become pregnant during the 

89 first year of use, based mainly on clinical trial data, for various birth control methods.

90

Approximate Percentage of Women Who Become Pregnant During the First Year of Use of a Birth Control Method*

METHOD PREGNANCIES PER 100 WOMEN PER YEAR

estrogen/progestin injection

levonorgestrel implants

levonorgestrel IUD and copper IUD 

medroxyprogesterone acetate injection

sterilization 

Fewer than 1

estrogen/progestin contraceptive products:

• pills 

• skin patch 

• vaginal ring

1

progestin-only pills 2

condom (male)

diaphragm

15

spermicides 25 or more

* 91 The estimates for drugs, condoms, diaphragms, and IUDs are derived from clinical trial data reviewed by the Food 

92 and Drug Administration. The estimates for sterilization and spermicides come from the medical literature.

93

94

95 Clinical Studies

96

97 This section can contain a brief description of the extent of the Phase III program, such as the 

98 number of patients, the number of patients less than 35 years old, the number of treatment 

99 months. This section can also be used when there is an efficacy or safety issue specific to the 

100 product that is not addressed in class labeling. The location of this section may vary, depending 

101 on content.

102
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103 CONTRAINDICATIONS

104

105 OCs should not be used by women who have the following conditions: 

106

107 • Breast cancer or other hormone-sensitive cancer, now or in the past

108 • Liver tumors, now or in the past, or liver disease 

109 • Undiagnosed abnormal genital bleeding

110 • Any condition predisposing to thrombotic diseases

111 • Thrombophlebitis or pulmonary embolism, now or in the past

112 • Cerebrovascular disease

113 • Coronary artery disease

114 • Thrombogenic valvular or thrombogenic rhythm diseases of the heart

115 • Congenital hypercoagulopathies

116 • Diabetes with vascular disease

117 • Uncontrolled hypertension

118 • Migraines with focal neurologic symptoms

119 • Smoking and over age 35

120 • Pregnancy

121 • Allergy to any components of this drug product

122

123 WARNINGS

124

125 The use of OCs with estrogen and progestin increases the risk of serious conditions, including 

126 myocardial infarction, thromboembolism, stroke, hepatic neoplasia, and gallbladder disease. 

127 However, the risk of serious morbidity or mortality is small in healthy women without 

128 underlying risk factors. When considering OCs for a woman with underlying risk factors, the 

129 risks of pregnancy and the feasibility of other birth control methods must also be considered. 

130

131 Minimizing exposure to estrogen and progestin reduces the risk of thrombotic events. For any 

132 particular estrogen/progestin combination, the recommended dosage regimen is that which 

133 contains the least amount of estrogen and progestin that is compatible with a low pregnancy rate 

134 and the medical needs of the individual patient.

135

136 1. Vascular Risks

137

138 a. Mortality

139

140 For nonsmokers, the risk of cardiovascular death from OC use is less than the risk of death from 

141 pregnancy. However, for smokers over age 35, the risk of cardiovascular death from OC use is 

greater than the risk of death from pregnancy for women over age 35.1142

143

144 b. Thromboembolism

145

146 Observational studies suggest an increased risk of superficial thrombophlebitis, deep vein 

thrombosis, and pulmonary embolism in OC users compared to non-OC users.2,3,4,5,6,7,8,9,10 147 The risk 
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148 of thromboembolic disease associated with OCs is not related to length of use and disappears after 

use of the drug product is stopped.2149

150

151 A 2- to 4-fold increase in relative risk of postoperative thromboembolic complications has been 

reported with the use of OCs.7152 The relative risk of venous thrombosis in women who have 

predisposing conditions is twice that of women without such medical conditions.11 153 If feasible, OCs 

154 should be stopped at least 4 weeks before through 2 weeks after elective surgery of a type associated 

with an increase in risk of thromboembolism and during prolonged immobilization.12,13 155

156

157 OCs should be started no earlier than 3 to 4 weeks after delivery in women who elect not to breast158 feed. The increased risk of thromboembolism in the postpartum period appears to decrease after the 

third postpartum week, whereas the risk of ovulation increases after the third postpartum week. 14,15 159

160

161 OCs are associated with retinal vein thrombosis in case reports. OCs should be discontinued if 

162 there is unexplained partial or complete loss of vision; onset of proptosis or diplopia, papilledema, 

163 or retinal vascular lesions. Symptoms of retinal vein thrombosis should be evaluated 

immediately.16,17,18 164

165

OC use may also increase the risk of thrombosis in women with valvular heart conditions19 166 or 

167 arrhythmias that predispose to thrombosis, such as atrial fibrillation. 

168

169 The presence of factor V Leiden mutation and other hereditary or acquired coagulation disorders 

increases the risk of thromboembolic disease.20 170

171

172 For desogestrel containing products: Several epidemiologic studies indicate that OCs containing 

173 desogestrel are associated with a higher risk of venous thromboembolism than OCs containing 

174 other progestins. In general, these studies indicate an approximate 2-fold increased risk, which

175 corresponds to an additional 1 to 2 cases of venous thromboembolism per 10,000 women-years of 

176 use. However, data from other studies have not shown this 2-fold increase in risk. 

177

178 c. Myocardial infarction

179

180 An increased risk of myocardial infarction is attributed to OC use. This risk is mainly in women 

181 with underlying risk factors for coronary artery disease such as smoking, hypertension, 

182 hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current OC 

users compared to nonusers is estimated to be two to six.21,22,23,24,25,26,27 183 The risk is very low under 

184 the age of 30.

185

186 Smoking in combination with OC use contributes substantially to the incidence of myocardial 

187 infarctions in women in their mid-30s or older, with smoking accounting for the majority of excess 

188 cases. In one study, the relative risk of myocardial infarction in heavy smokers who use OCs was 

39, compared to 4.9 for nonsmokers who use OCs, and 1.0 for nonsmokers who do not use OCs.28 189 

190 Estimates of the annual mortality rate from cardiovascular disease in OC users over age 35 show a 

five-fold higher risk for smokers compared to nonsmokers.29 191

192
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193 OCs must be used with caution in women with cardiovascular disease risk factors. OCs may further 

194 increase the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age, 

and obesity. 30 195

196

197 d. Cerebrovascular diseases

198

199 In observational studies, OCs appear to increase the risk of strokes, although, in general, the risk is 

greatest among hypertensive women over age 35 who also smoke. 31,32,33 200

201

202 The relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 

for users with severe hypertension.34 203 The relative risk of hemorrhagic stroke is reported to be 1.2 

204 for nonsmokers who used OCs, 2.6 for smokers who did not use OCs, 7.6 for smokers who used 

OCs, 1.8 for normotensive users, and 25.7 for users with severe hypertension.24 205

206

207 e. Dose-related risk of vascular disease from OCs 

208

209 A positive association has been observed between the amount of estrogen and progestin in OCs and 

the risk of vascular disease.35,36,37 210 A decline in serum high-density lipoproteins (HDL) is seen with 

many progestational agents.38,39,40 211

212

213 2. Carcinoma of the Breast and Cervix

214

215 Women who currently have or have had breast cancer should not use oral contraceptives because 

216 breast cancer may be hormonally sensitive.

217

There is substantial evidence that OCs do not increase the incidence of breast cancer.41,42 218 Although 

219 some past studies have suggested that OCs might increase the incidence of breast cancer, more 

220 recent and thoroughstudies have not confirmed such findings. 

221

222 Some studies suggest that OCs are associated with an increase in the risk of cervical cancer or 

intraepithelial neoplasia.43,44,45,46 223 However, there is controversy about the extent to which these 

224 findings are due to differences in sexual behavior and other factors.

225

226 3. Liver Disease

227

228 Benign hepatic adenomas are associated with OC use. Indirect calculations have estimated the 

attributable risk to be 3.3 cases/100,000 for OC users.47 229 Rupture of benign, hepatic adenomas may 

cause death through intra-abdominal hemorrhage.48,49 230

231

232 Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in longterm (more than 8 years) OC users.50,51,52,53 233 However, the attributable risk (the excess incidence) of 

234 liver cancers in OC users is less than one per million users.

235

236 OC-related cholestasis has been described in women with a history of pregnancy-related cholestasis. 

237 Women with a history of OC-related cholestasis may have the condition recur with subsequent OC 

use.54 238
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239 

240 OCs should be discontinued if jaundice develops. Steroid hormones may be poorly metabolized in 

241 patients with impaired liver function.

242

243 4. Gallbladder Disease

244

245 Studies have shown that the increased relative risk of developing gallbladder disease among OC 

users may be minimal.55,56,57,58,59,60,61 246

247

248 5. Carbohydrate and Lipid Metabolic Effects

249

OCs may decrease glucose tolerance in a dose-related fashion.62,63 250 Therefore, prediabetic and 

251 diabetic women should be carefully monitored while taking OCs. However, in nondiabetic women, 

OCs appear to have no effect on fasting blood glucose.64 252

253

254 A small proportion of women will have adverse lipid changes while on OCs. Alternative 

contraception should be considered in women with uncontrolled dyslipidemias.65 255 Elevations of 

256 plasma triglycerides may lead to pancreatitis and other complications.

257

258 6. High Blood Pressure

259

260 Women with uncontrolled hypertension or hypertension with vascular disease should not use 

OCs.66,67,68 An increase in blood pressure has been reported in women taking OCs,69 261 and this 

increase is more likely in older OC users70 262 and with extended duration of use. Data from the Royal 

College of General Practitioners71 263 and subsequent randomized trials have shown that the incidence 

264 of hypertension increases with increasing progestational activity and concentrations of progestins. 

265 If OCs are prescribed for women with well-controlled hypertension, close blood pressure 

266 monitoring is recommended and OCs should be discontinued if blood pressure rises significantly.

267

268 7. Headache

269

270 The onset or exacerbation of migraine or development of headache with a new pattern that is 

271 recurrent, persistent, or severe requires discontinuation of OCs and evaluation of the cause.

272

273 8. Vaginal Bleeding Problems

274

275 Breakthrough bleeding and spotting are sometimes seen in patients on OCs, especially during the 

276 first 3 months of use. If bleeding persists, nonhormonal causes such as pregnancy or malignancy 

277 should be considered. If pathology and pregnancy are excluded, time or a change to another 

278 formulation may solve the problem. 

279

280 Amenorrhea is sometimes seen in women who are using OCs. Pregnancy should be ruled out in the 

281 event of amenorrhea.

282

283 A description of vaginal bleeding patterns from the controlled clinical trials that supported drug 

284 approval should be placed here if relevant.
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285

286 PRECAUTIONS

287

288 1. General 

289

290 Women who are using oral contraceptives should have an annual history and physical 

291 examination, including special reference to blood pressure, breasts, abdomen and pelvic organs, 

292 as well as cervical cytology and relevant laboratory tests. 

293

294 2. Information for Patients

295

296 See patient labeling.

297

298 3. Hypocalcemia

299

300 Estrogens should be used with caution in individuals with severe hypocalcemia because this 

301 condition may be aggravated.

302

303 4. Drug Interactions

304

305 Changes in contraceptive effectiveness associated with co-administration of other products:

306

307 a. Anti-infective agents and anticonvulsants

308

309 Contraceptive effectiveness may be reduced when hormonal contraceptives are co-administered 

310 with antibiotics, anticonvulsants, and other drugs that increase the metabolism of contraceptive 

steroids.72 311 This could result in unintended pregnancy or breakthrough bleeding. Some examples 

312 include rifampin, barbiturates, phenylbutazone, phenytoin, carbamezepine, felbamate, 

313 oxcarbazepine, topiramate, and griseofulvin. 

314

315 b. Anti-HIV protease inhibitors

316

317 Several of the anti-HIV protease inhibitors have been studied with co-administration of oral 

318 combination hormonal contraceptives; significant changes (increase and decrease) in the plasma 

319 levels of the estrogen and progestin have been noted in some cases. The safety and efficacy of OC 

320 products may be affected with co-administration of anti-HIV protease inhibitors. Health care 

321 providers should refer to the label of the individual anti-HIV protease inhibitors for further drug322 drug interaction information.

323

324 c. Herbal products

325

326 Herbal products containing St. John’s Wort (hypericum perforatum) may induce hepatic enzymes 

327 (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of 

328 contraceptive steroids. This may also result in breakthrough bleeding. 

329
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330 Increase in plasma levels of estradiol associated with co-administered drugs:

331

332 Co-administration of atorvastatin and certain OCs containing ethinyl estradiol increase AUC values 

333 for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma 

334 ethinyl estradiol levels, possibly by inhibition of conjugation. CYP 3A4 inhibitors such as 

335 itraconazole or ketoconazole may increase plasma hormone levels.

336

337 Changes in plasma levels of co-administered drugs:

338

339 Combination hormonal contraceptives containing some synthetic estrogens (e.g., ethinyl estradiol) 

340 may inhibit the metabolism of other compounds. Increased plasma concentrations of cyclosporin, 

341 prednisolone, and theophylline have been reported with concomitant administration of OCs. 

342 Decreased plasma concentrations of acetaminophen and increased clearance of temazepam, salicylic 

343 acid, morphine and clofibric acid, due to induction of conjugation have been noted when these 

344 drugs were administered with OCs.

345

346 5. Interactions with Laboratory Tests

347

348 Certain endocrine and liver function tests and blood components may be affected by OCs:

349

350 a. Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased 

351 norepinephrine-induced platelet aggregability. 

352

353 b. Increased thyroid binding globulin (TBG) leading to increased circulating total thyroid 

354 hormone, as measured by protein-bound iodine (PBI), T4 by column or by 

355 radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG, free T4 

356 concentration is unaltered. Patients dependent on thyroid hormone replacement therapy who 

357 are also receiving estrogens may require increased doses of their thyroid replacement 

358 therapy. 

359

360 c. Other binding proteins may be elevated in serum. 

361

362 d. Sex hormone binding globulins are increased and result in elevated levels of total circulating 

363 sex steroids; however, free or biologically active levels either decrease or remain unchanged. 

364

365 e. Triglycerides may be increased and levels of various other lipids and lipoproteins may be 

366 affected. 

367

368 f. Glucose tolerance may be decreased. 

369

370 6. Carcinogenesis, Mutagenesis, Impairment of Fertility

371

372 See CONTRAINDICATIONS and WARNINGS (subsection 2. Carcinoma of the Breast 

373 and Cervix). If the OC contains a new progestin or estrogen, data on animal carcinogenicity, 

374 mutagenicity, and return to fertility should be placed here.
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375

376 7. Pregnancy

377

378 There appears to be little or no increased risk of birth defects in women who have used OCs 

inadvertently during early pregnancy. 73,74 379 However, if any component of the drug product is

380 associated with birth defects, add a statement about the types of defects, estimated frequency, the 

381 associated doses, and the gestational age of exposure, if known. 

382

383 If the OC contains a new progestin or estrogen, a statement that summarizes what is known about 

384 pregnancy risk should be placed here, followed by a summary of the animal/human data.

385

386 8. Nursing Mothers

387

388 Small amounts of OC steroids have been identified in the milk of nursing mothers. In addition, OCs 

389 given in the postpartum period may interfere with lactation by decreasing the quantity and quality of 

390 breast milk. If possible, the nursing mother should be advised to use other forms of contraception 

391 until she has weaned her child.

392

393 9. Pediatric Use

394

395 Safety and efficacy are expected to be the same for postpubertal adolescents and adult women. OCs 

396 are not indicated before menarche.

397

398 10. Geriatric Use

399

400 OCs have not been studied in postmenopausal women and are not indicated in this population. 

401

402 ADVERSE EXPERIENCES

403

404 The most serious adverse reactions associated with the use of OCs are in the WARNINGS and 

405 PRECAUTIONS sections.

406

407 Other side effects commonly reported by OC users are:

408 • Nausea

409 • Breast tenderness

410 • Headaches

411

412 The following adverse reactions may occur less frequently:

413 • Acne 

414 • Decreased libido

415 • Dizziness 

416 • Fluid retention 

417 • Increased cervical ectopia 
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418 • Melasma 

419 • Mood changes and depression

420 • Ocular effects, including decreased tolerability to contact lenses

421 • Vaginal candidiasis

422 • Vomiting and other gastrointestinal symptoms (e.g., bloating)

423 • Weight changes

424

425 It is not always clear whether these side effects are caused by OCs and, if so, whether the 

426 estrogen and/or the progestin is responsible. These side effects are most common in the first 1 to 

427 3 pill cycles.

428 Manufacturers should add additional details regarding adverse experiences and cycle control 

429 unique to the product.

430

431 POSSIBLE HEALTH BENEFITS

432

433 Possible benefits associated with OC use beyond lowering of risk of becoming pregnant include the 

434 following effects on menses:

435

436 • More regular

437 • Less blood loss 

438 • Less dysmenorrhea 

439

440 OVERDOSAGE

441

442 There have been no reports of serious ill effects from overdose, including ingestion by children. 

443 Overdose may cause nausea and withdrawal bleeding.

444

445 DOSAGE AND ADMINISTRATION

446

447 To achieve maximum contraceptive effectiveness, OCs must be taken as directed. One tablet is 

448 taken at about the same time every day. Single missed pills should be taken as soon as 

449 remembered. For detailed instructions, see the patient labeling that is printed below.

450

451 OCs may be started 3 to 4 weeks postpartum in women who do not breast feed. When OCs are 

452 used during the postpartum period, the increased risk of thromboembolic disease associated with 

the postpartum period must be considered.14 453 The possibility of ovulation and conception before 

starting OCs should also be considered.15 454

455
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456 HOW SUPPLIED

457

458 Manufacturer to provide information on available dosage forms, potency, color, and packaging.

459

460 Manufacturer to include statement such as "Keep out of reach of children."

461

462 STORAGE

463

464 Manufacturer to provide information on pill storage.

465

466 REFERENCES 

467

468 Supplied upon request.

469
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470 III. PATIENT LABELING 

471

472

473 Guide for Using (OC name)

474

475

476 WARNING TO WOMEN WHO SMOKE

477

478 Do not use (OC name) if you smoke cigarettes and are over 35 years old. Smoking increases 

479 your risk of serious side effects from birth control pills, including death from heart attack, blood 

480 clots, or stroke. The risk increases with age and the number of cigarettes you smoke. 

481

482 Birth control pills help to lower the chances of becoming pregnant. They do not protect 

483 against HIV infection (AIDS) and other sexually transmitted diseases.

484

485

486 WHAT IS (OC NAME)?

487

488 (OC name) is a birth control pill. It contains two hormones, an estrogen called (name of 

489 estrogen), and a progestin called (name of progestin).

490

491

492 HOW WELL DOES (OC NAME) WORK?

493

494 Your chance of getting pregnant depends on how well you follow the directions for taking your 

495 birth control pills. The more carefully you follow the directions, the less chance you have of 

496 getting pregnant.

497

498

499 In clinical studies, about (insert whole number here) out of 100 women got pregnant during the 

500 first year that they used (insert OC name here).

501

502

503 The following table shows how the birth control pill compares with some other methods of birth 

504 control. The numbers are estimates of the number of women out of 100 women who become 

pregnant in 1 year of use.2505

506

 

2

 The estimates for drugs and devices come from clinical trial data reviewed by the Food and Drug Administration. 

The IUDs include the levonorgestrel IUD and the copper IUD. The estimates for sterilization and spermicides come 

from the medical literature. 
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507

508 HOW DO I TAKE (OC NAME)?

509

510 Consider the instructions given to women during clinical trials when crafting the text for this 

511 section. To minimize errors, all OC instructions should be similar, but some differences are 

512 inevitable because of the diversity of OCs.

513

514 To improve clarity, place the instructions for only one brand and regimen in the patient label for 

515 a given birth control pill. For example, package only 21-day pill instructions with 21-day pills, 

516 and only 28-day pill instructions with 28-day pills.

517

518 Insert illustration of pill pack, direction in which pills are taken, and other labeling that might 

519 make the directions clearer, such as which pills are active and which are inactive.

520 The sample answers below apply to an imaginary birth control pill named Brand X, a 28-day 

521 pack with 21 active pills. In the Brand X clinical trials, women were told to start the first pack 

522 on day 1 of their menstrual periods. Brand X instructions do not include Sunday Start 

523 instructions because Sunday Start was not studied in the clinical trials.

524

525 If you have regular periods, take the first pill of the first pack on the first day of your period. If 

526 you are not having regular periods, talk with your health care provider about when to start your 

527 birth control pill. 

Number of women

out of 100 who

become pregnant in

1 year

Birth Control Method

Fewer than 1 Sterilization, implants, intrauterine device (IUD), injection

1 Birth control pills, skin patch, vaginal ring with hormones

15 Condom, diaphragm

25 or more Spermicides

Fewer

Pregnancies

More

Pregnancies
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528

529 Take one pill about the same time every day. Taking a pill every day must become a habit. 

530

531 When you finish a pill pack, start the next pack on the following day so you are always taking 

532 one pill a day, whether or not you are having your period. You are more likely to get pregnant if 

533 you start the next pack late or miss any pills.

534

535 Look at the picture of your pill pack. There are 21 active (insert color here) pills that contain 

536 hormones and 7 inactive (insert color here) pills that do not contain hormones. You are most 

537 likely to have your period during the time you are taking the inactive pills.

538

539 WHAT SHOULD I DO IF I MISS ANY BIRTH CONTROL PILLS?

540

541 As noted in the preceding question, consider the instructions given to women during clinical 

542 trials when crafting the text for this section. The sample answers for Brand X follow.

543

544 Use a backup birth control method such as condoms or spermicide for 7 days after you miss any 

545 of the active (insert color here) pills.

546

547 If you miss 1 active (insert color here) pill take it as soon as you remember. Take the next pill at 

548 your regular time. You may take 2 pills in 1 day. 

549

550 If you miss 2 active (insert color here) pills in a row in week 1 or week 2 of your pack, take 2 

551 pills as soon as you remember and 2 pills the next day. Then take 1 pill a day until you finish the 

552 pack.

553

554 If you miss 2 active (insert color here) pills in a row in week 3 of your pack, throw out the rest 

555 of the pack and start a new pack that same day. You may not have your period this mo nth. 

556 However, if you miss 2 periods in a row, call your health care provider to check for pregnancy.

557

558 If you miss 3 or more active (insert color here) pills in a row during the first 3 weeks, throw out 

559 the rest of the pack and start a new pack that same day. Call your health care provider for further 

560 advice.

561

562 If you forget any of the (insert color here) inactive pills, throw away the pills you missed and 

563 continue to take one pill a day. You do not need a backup method.

564
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565 WHO SHOULD NOT TAKE (OC NAME)?

566

567 Birth control pills are safe for most women. However, taking birth control pills can cause 

568 serious health problems, especially for women with certain conditions. Do not take (name of 

569 OC) if you have:

570

571 • Ever had breast cancer or any cancer that is sensitive to hormones

572 • Liver disease, including liver tumors

573 • Unexplained bleeding from your vagina

574 • Ever had blood clots in your arms, legs, or lungs 

575 • Ever had a stroke

576 • Ever had a heart attack or chest pains 

577 • Certain heart valve problems or heart rhythm abnormalities that can cause blood clots to 

578 form in the heart

579 • An inherited problem with your blood that makes it clot more than normal

580 • High blood pressure that medicine can't control

581 • Diabetes with kidney, eye, or blood vessel damage

582 • Severe migraine headaches

583

584 Also, do not take birth control pills if you:

585

586 • Smoke and are over 35 years old

587 • Are pregnant

588 • Are allergic to anything in (OC)

589

590 If applicable, the following statement is inserted here: The risks for serious blood clots may be 

591 greater with desogestrel-containing pills such as (name of OC) than with certain other birth 

592 control pills.

593

594 Birth control pills may not be a good choice for you if you have ever had jaundice (yellowing of 

595 the skin or eyes) caused by pregnancy, also called cholestasis of pregnancy. 

596

597 WHAT ELSE SHOULD I KNOW ABOUT TAKING (OC NAME)?

598

599 Do not skip any pills, even if you do not have sex often.

600
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601 If you miss a period, you could be pregnant. However, some women miss periods or have light 

602 periods on birth control pills, even when they are not pregnant. Contact your health care 

603 provider for advice if you:

604

605 • Think you are pregnant

606 • Miss 1 period and have not taken your birth control pills according to directions

607 • Miss 2 periods 

608

609 Birth control pills should not be taken during pregnancy. However, birth control pills taken by 

610 accident during pregnancy do not seem to cause birth defects. If the OC contains a new 

611 progestin or estrogen, note that fact and summarize what is known about pregnancy risk here. If

612 any component of the drug product is associated with birth defects, add a statement about the 

613 types of defects, estimated frequency, the associated doses, and the gestational age of exposure, 

614 if known.

615

616 You should consider another birth control method if you are breast-feeding because birth control 

617 pills ma y decrease the amount and quality of your milk. A small amount of the pill's hormones 

618 are passed on to your baby in your milk. 

619

620 If you need laboratory tests, tell your health care provider that you are taking birth control pills. 

621 Birth control pills may affect some blood tests.

622

623 Tell your health care provider about all medicines and herbal products that you take. Some 

624 medicines and herbal products may make birth control pills less effective. Some examples are 

625 rifampin, medicines used for epilepsy (such as barbiturates, topiramate, carbamazepine, and 

626 phenytoin), phenylbutazone, certain medicines used to treat HIV or AIDS, certain antibiotics, 

627 and the herbal product St. John's Wort. Consider using another birth control method when you 

628 take medicines that may make birth control pills less effective.

629

630 If you have vomiting or diarrhea, your birth control pills may not work as well. Use another 

631 birth control method, like condoms, until you check with your health care provider.

632

633 WHAT ARE COMMON SIDE EFFECTS OF BIRTH CONTROL PILLS?

634

635 The most common side effects of birth control pills are:

636

637 • Nausea 

638 • Breast tenderness

639 • Headache

640 • Bleeding between menstrual periods

641

642 These side effects are usually mild and may disappear with time.

643
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644 Less common side effects are:

645

646 • Bloating or fluid retention.

647 • Darkening of the skin, especially on the face. This problem may be related to the 

648 darkening of the skin that sometimes happens during pregnancy.

649 • High blood sugar, especially in women who already have diabetes.

650 • High triglycerides (high fat levels in the blood).

651 • Depression, especially if you have had depression in the past. Call your health care 

652 provider immediately if you have any thoughts of harming yourself.

653 • Weight changes.

654

655 This is not a complete list of possible side effects. Talk to your health care provider if you 

656 develop any side effects that concern you.

657

658 No serious problems have been reported from a birth control pill overdose, even when 

659 accidentally taken by children.

660

661 WHAT ARE THE MOST SERIOUS RISKS OF TAKING BIRTH CONTROL PILLS?

662

663 Like pregnancy, birth control pills increase the risk of serious blood clots. It is possible to die 

664 from a problem caused by a blood clot, such as a heart attack or a stroke. Some examples of 

665 serious blood clots are blood clots in the:

666

667 • Legs (thrombophlebitis)

668 • Lungs (pulmonary embolus) 

669 • Eyes (blindness)

670 • Heart (heart attack)

671 • Brain (stroke)

672

673 A few women who take birth control pills may get:

674

675 • Rare cancerous or noncancerous liver tumors

676 • Gallbladder problems

677 • High blood pressure

678

679
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680 Call your health care provider right away if you have:

681

682 • Persistent pain in the calf (lower leg)

683 • Sudden shortness of breath 

684 • Sudden blindness, partial or complete 

685 • Severe pain in your chest

686 • Sudden, severe headache

687 • Weakness or numbness in an arm or leg, or trouble speaking

688 • Yellowing of the skin or eyeballs

689

690 DO BIRTH CONTROL PILLS CAUSE CANCER?

691

692 Birth control pills do not seem to cause breast cancer. However, if you have breast cancer now, 

693 or have had it in the past, do not use birth control pills because some breast cancers are sensitive 

694 to hormones. 

695

696 Women who use birth control pills may have a slightly higher chance of getting cervical cancer. 

697 However, this may be due to other reasons such as having more sexual partners.

698

699

700 WHAT IF I WANT TO BECOME PREGNANT?

701

702 Consider a visit with your health care provider for a pre-pregnancy checkup before you stop 

703 taking the pill. Your health care provider may advise you to wait for your first regular period 

704 before you try to become pregnant. A daily dose of the vitamin called folic acid is recommended 

705 for all women who are planning a pregnancy. 

706

707 ARE THERE OTHER BENEFITS OF THE BIRTH CONTROL PILL?

708

709 Yes. Your menstrual periods may become:

710

711 • More regular

712 • Lighter

713 • Less painful

714

715

716

717

718 General Advice about (OC name)

719

720 Your health care provider prescribed (OC name) for you. Please do not share (OC name) with 

721 anyone else. Keep (OC name) out of the reach of children.

722

723 Birth control pills are sometimes prescribed for reasons other than those listed in your Guide. If 

724 you have concerns or questions, ask your health care provider. You may also ask your health

725 care provider for a more detailed label written for medical professionals. 
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726

727 List the name and place of business of the manufacturer, packer, or distributor of OC here.

728

729 Write the date of the most recent revision of the Guide here.

730

731

732

733

 

1 Schwingl PJ, Ory HW, and Visness CM. Estimates of the risk of cardiovascular death attributable to 

low-dose oral contraceptives in the United States. Am J Obstet Gynecol 1999; 180:241-249

2

 Stadel BV. Oral contraceptives and cardiovascular disease. (Pt.1). N Engl J Med 1981; 305:612-618

3

 Stadel BV. Oral contraceptives and cardiovascular disease. (Pt.2). N Engl J Med 1981; 305:672-677

4

 Inman WH, Vessey MP. Investigation of death from pulmonary, coronary, and cerebral thrombosis and 

embolism in women of child-bearing age. Br Med J 1968; 2(5599):193-199

5

 Maguire MG, Tonascia J, Sartwell PE, Stolley PD, Tockman MS. Increased risk of thrombosis due to 

oral contraceptives: a further report. Am J Epidemiol 1979; 110(2):188-195

6 Petitti DB, Wingerd J, Pellegrin F, Ramacharan S. Risk of vascular disease in women: smoking, oral 

contraceptives, noncontraceptive estrogens, and other factors. JAMA 1979; 242:1150-1154

7 Vessey MP, Doll R, Investigation of relation between use of oral contraceptives and thromboembolic 

disease. Br Med J 1968; 2(5599):199-205

8

 Vessey MP, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic 

disease. A further report. Br Med J 1969; 2(658):651-657

9

 Porter JB, Hunter JR, Danielson DA, Jick H, Stergachis A. Oral contraceptives and non-fatal vascular 

disease-recent experience. Obstet Gynecol 1982; 59(3):299-302

10Vessey M, Doll R, Peto R, Johnson B, Wiggins P. A long-term follow-up study of women using different 

methods of contraception: an interim report. J Biosocial Sci 1976; 8:375-427

11 Royal College of General Practitioners: Oral Contraceptives, venous thrombosis, and varicose veins. J 

Royal Coll Gen Pract 1978; 28:393-399

12 Guillebaud, J. Surgery and the pill. Br Med J 1985; 29:498-499

13 Robinson GE, Burren T, Mackie IJ, Bounds W, Walshek, et al. Changes in haemostasis after stopping 

the combined contraceptive pill: implications for major surgery. Br Med J 1991;302: 269-271

14 Dahlman T, Hellgren M, Blombach M. Changes in blood coagulation and fibrinolysis in the normal 

puerperium. Gynecol Obstet Invest 1985; 20:37-44

15 Gray RH, Campbell OM, Zacur HA, Labbok MH, MacRae SL. Postpartum return of ovarian activity in 

nonbreastfeeding women monitored by urinary assays. J Clin Endocrin Metabol 1987; 64(4):645-650

16 Jaais F, Habib, ZA. Unilateral superior ophthalmic vein thrombosis in a user of oral contraceptives. Med 

J Malaysia 1994; 49:416-418
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17 Leong KC, Tan PL. Central retinal vein thrombosis in a woman on contraceptive pills. Singapore Med J 

1974; 15:156-157

18 Varga M. Recent experience on the ophthalmologic complications of oral contraceptives. Ann 

Ophthalmol 1976; 8:925-934

19 WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Acute 

myocardial infarction and combined oral contraceptives: results of an international multicentre casecontrol study. Lancet 1997; 349:1202-1209

20 Vandenbroucke JP, Koster T, Briet E, Teitsma PH, Bertina RM, Rosendaal FR. Increased risk of 

venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994;

334:1453-1457

21 Adam SA, Thorogood M. Oral contraception and myocardial infarction revisited: the effects of new 

preparations and prescribing patterns. Br J Obstet Gynaecol 1981; 88:838-845

22 Mann Jl, Inman WH. Oral contraceptives and death from myocardial infarction. Br Med J 1975; 

2(5965):245-248

23 Mann JI, Vessey MP, Thorogood M, Doll R. Myocardial infarction in young women with special 

reference to oral contraceptive practice. Br Med J 1975; 2(5959):241-245

24 Royal College of General Practitioners' Oral Contraception Study. Further analyses of mortality in oral 

contraceptive users. Lancet 1981; 1:541-546.

25 Slone D, Shapiro S, Kaufman DW, Rosenberg L, Miettinene OS, Stolley PD. Risk of myocardial 

infarction in relation to current and discontinued use of oral contraceptives. N Engl J Med 1981; 305:420-

424

26 Vessey MP. Female hormones and vascular disease-an epidemiological overview. Br J Fam Plann 

1980; 6(Supplement):1-12

27 Russell-Briefel RG, Ezzati TM, Fulwood R, Perlman JA, Murphy RS. Cardiovascular risk status and 

oral contraceptive use, United States 1976-80. Prevent Med 1986; 15:352-362

28 Goldbaum GM, Kendrick JS, Hogelin GC, Gentry EM. The relative impact of smoking and oral 

contraceptive use on women in the United States. JAMA 1987; 258:1339-1342

29 Schwingl, PJ, Ory HW, Visness CM. Estimates of the risk of cardiovascular death attributable to lowdose oral contraceptives in the United States. Am J Obstet Gynecol 1999; 180:241-249

30 Knopp RH. Arteriosclerosis risk: the roles of oral contraceptives and postmenopausal estrogens. J 

Reprod Med 1986; 31(9) (Supplement):913-921

31 Collaborative Group for the Study of Stroke in Young Women. Oral contraception and increased risk of 

cerebral ischemia or thrombosis. N Engl J Med 1973; 288:871-878

32 Petitti DB, Wingerd J. Use of oral contraceptives, cigarette smoking, and risk of subarachnoid 

hemorrhage. Lancet 1978; 2:234-236

33 Inman WH. Oral contraceptives and fatal subarachnoid hemorrhage. Br Med J 1979; 2(6203):1468-

1470
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34 Collaborative Group for the Study of Stroke in Young Women. Oral Contraceptives and stroke in young 

women: associated risk factors. JAMA 1975; 231:718-722

35Inman WH, Vessey MP, Westerholm B, Engelund A. Thromboembolic disease and the steroidal content 

of oral contraceptives. A report to the Committee on Safety of Drugs. Br Med J 1970; 2:203-209 

36 Meade TW, Greenberg G, Thompson SG. Progestogens and cardiovascular reactions associated with 

oral contraceptives and a comparison of the safety of 50- and 35-microgram oestrogen preparations. Br 

Med J 1980; 280(6224):1157-1161

37 Kay CR. Progestogens and arterial disease--evidence from the Royal College of General Practitioners' 

Study. Am J Obstet Gynecol 1982; 142:762-765

38 Krauss RM, Roy S, Mishell DR, Casagrande J, Pike MC. Effects of two low-dose oral contraceptives 

on serum lipids and lipoproteins: differential changes in high-density lipoprotein subclasses. Am J Obstet 

1983; 145:446-452

39 Wahl P, Walden C, Knopp R, Hoover J, Wallace R, et al. Effect of estrogen/progestin potency on 

lipid/lipoprotein cholesterol. N Engl J Med 1983; 308:862-867

40 Wynn V, Niththyananthan R. The effect of progestin in combined oral contraceptives on serum lipids

with special reference to high-density lipoproteins. Am J Obstet Gynecol 1982;142:766-771

41 Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal 

contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 

100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996; 347:1713-1727

42 Marchbanks PA, McDonald JA, Wilson HG, Folger SG, Madel MG, et al. Oral contraceptives and the 

risk of breast cancer. N Engl J Med 2002; 346:2025-2032

43 Vessey MP, Lawless M, McPherson K, Yeates D. Neoplasia of the cervix uteri and contraception: a 

possible adverse effect of the pill. Lancet 1983; 2:930

44 Brinton LA, Huggins GR, Lehman HF, Malli K, Savitz DA, et al. Long-term use of oral contraceptives 

and risk of invasive cervical cancer. Int J Cancer 1986; 38:339-344

45WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Invasive cervical cancer and 

combined oral contraceptives. Br Med J 1985; 290:961-965 

46 Moreno V, Bosch FX, Munoz N, Meijer CJLM, Shah KV, et al. Effect of oral contraceptives on risk of 

cervical cancer in women with human papillomavirus infections: the IARC multicentric case-control study. 

Lancet 2002; 359:1085-1092

47 Rooks JB, Ory HW, Ishak KG, Strauss LT, Greenspan JR, et al. Epidemiology of hepatocellular 

adenoma: the role of oral contraceptive use. JAMA 1979; 242:644-648

48 Bein NN, Goldsmith HS. Recurrent massive hemorrhage from benign hepatic tumors secondary to oral 

contraceptives. Br J Surg 1977; 64:433-435

49 Klatskin G. Hepatic tumors: possible relationship to use of oral contraceptives. Gastroenterology 1977; 

73:386-394

50 Henderson BE, Preston-Martin S, Edmondson HA, Peters RL, Pike MC. Hepatocellular carcinoma and 

oral contraceptives. Br J Cancer 1983; 48:437-440
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51 Neuberger J, Forman D, Doll R, Williams R. Oral contraceptives and hepatocellular carcinoma. Br Med 

J 1986; 292:1355-1357

52 Forman D, Vincent TJ, Doll R, Cancer of the liver and oral contraceptives. Br Med J 1986; 292:1357-

1361

53 Palmer JR, Rosenberg L, Kaufman DW, Warshauer ME, Stolley P, et al. Oral contraceptive use and 

liver cancer. Am J Epidemiol 1989; 130:878-882

54 Lindberg MC. Hepatobiliary complications of oral contraceptives. J of Gen Intern Med 1992; 7:199-209

55 Thijs C, Knipschild P. Oral contraceptives and the risk of gallbladder disease: a meta-analysis. Am J 

Public Health 1993; 83:1113-1120

56 Vessey M, Painter R. Oral contraceptive use and benign gallbladder disease; revisited. Contracept Rep 

1994; 50:167-73

57 Grodstein F, Colditz GA, Hunter DJ, Manson JE, Willett WC, et al. A prospective study of symptomatic 

gallstones in women: relation with oral contraceptives and other risk factors. Obstet Gynecol 1994;

84:207-214

58 Boston Collaborative Drug Surveillance Program. Oral contraceptives and venous thromboembolic 

disease, surgically confirmed gallbladder disease, and breast tumors. Lancet 1973; 1:1399-1404

59 Layde PM, Vessey MP, Yeates D. Risk of gallbladder disease: a cohort study of young women 

attending family planning clinics. J Epidemiol Community Health 1982; 36:274-278

60 Rome Group for Epidemiology and Prevention of Cholelithiasis (GREPCO): Prevalence of gallstone 

disease in an Italian adult female population. Am J Epidemiol 1984; 119:796-805

61 Storm BL, Tamragouri RT, Morse ML, Lazar EL, West SL, et al. Oral contraceptives and other risk 

factors for gallbladder disease. Clin Pharmacol Ther 1986; 39:335-341

62 Wynn V, Godsland I. Effects of oral contraceptives on carbohydrate metabolism. J Reprod Med 1986;

31(9)(Supplement):892-897

63 Wynn V, Adams PW, Godsland IF, Melrose J, Niththyananthan R, et al. Comparison of effects of 

different combined oral contraceptive formulations on carbohydrate and lipid metabolism. Lancet 1979; 

1:1045-1049

64 Perlman JA, Roussell-Briefel RG, Ezzati TM, Lieberknecht G. Oral glucose tolerance and the potency 

of oral contraceptive progestogens. J Chronic Dis 1985; 38:857-864

65 Knopp RH, LaRosa JC, Burkman RT Jr. Contraception and dyslipidemia. Am J Obstet Gynecol 

1993;168:1994-2005

66 Improving access to quality care in family planning: Medical eligibility criteria for contraceptive use. 

Second Edition. Geneva: WHO, Family and Reproductive Health, 2000

67 Laragh AJ. Oral contraceptives--induced hypertension--nine years later. Am J Obstet Gynecol 1976; 

126:141-147
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68 Ramcharan S, Peritz E, Pellegrin FA, Williams WT. Incidence of hypertension in the Walnut Creek 

Contraceptive Drug Study cohort. In Pharmacology of steroid contraceptive drugs. Garattini S, Berendes 

HW. Eds. New York, Raven Press, 1977; pp. 277-288, (Monographs of the Mario Negri Institute for 

Pharmacological Research Milan)

69 Royal College of General Practitioners' Oral Contraception Study. Effect on hypertension and benign 

breast disease of progestogen component in combined oral contraceptives. Lancet 1977; 1:624

70Fisch IR, Frank J. Oral contraceptives and blood pressure. JAMA 1977; 237:2499-2503 

71 Layde PM, Beral V. Further analyses of mortality in oral contraceptive users; Royal College of General 

Practitioners' Oral Contraception Study (Table 5). Lancet 1981; 1:541-546

72 Stockley I. Interactions with oral contraceptives. J Pharm 1976; 216:140-143

73 Briggs GG, Freeman RK, Yaffe SJ. Oral Contraceptives. In Drugs in pregnancy and lactation: a 

reference guide to fetal and neonatal risk. Fifth Edition. Maryland: Williams & Wilkins,1998, pp. 805-807

74 Reprotox®. Oral Contraceptives. From summary updated based on a complete literature search in 

February, 2001. http://www.tomescps.com/DATA/RX/RX1162.HTM