EXHIBIT 1020
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`EXHIBIT 1020EXHIBIT 1020
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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`DRAFT GUIDANCE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`This guidance document is being distributed for comment purposes only.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`publication of the Federal Register notice announcing the availability of the draft guidance.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
`
`I:\5197dft.doc
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`Petitioner Exhibit 1020
`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
`Page 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
`
`I:\5197dft.doc
`03/02/04
`
`Petitioner Exhibit 1020
`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
`Page 2
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`TABLE OF CONTENTS
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`INTRODUCTION................................................................................................................. 1
`I.
`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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`Contains Nonbinding Recommendations
`
`Draft — Not for Implementation
`
`Guidance for Industry1
`Labeling for Combined Oral Contraceptives
`
`This draft guidance, when finalized, will represent FDA's current thinking on this topic. It does not create
`or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an
`alternative approach if it satisfies the requirements of the applicable statutes and regulations. If you want
`to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If
`you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this
`guidance.
`
`I.
`
`INTRODUCTION
`
`This guidance describes the recommended labeling for health care providers and patient
`instructions for use for new drug applications (NDAs) and abbreviated new drug applications
`(ANDAs) for combined oral contraceptives (OCs) that contain estrogen and progestin. A draft
`guidance on this topic was issued for comment in June 2000. Many comments were received on
`the 2000 draft guidance and, as a result, many changes have been made to the guidance. Because
`of the many changes, we are making the guidance available again in draft to allow for additional
`public review and input. The references listed at the end of this guidance do not go in the
`labeling.
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`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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`Contains Nonbinding Recommendations
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`Draft — Not for Implementation
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`II.
`
`LABELING FOR PACKAGE INSERT
`
`We recommend the following labeling be used for combined oral contraceptives:
`
`PROPRIETARY NAME (ESTABLISHED NAME)
`
`Supplied by manufacturer
`
`WARNING: CIGARETTE SMOKING
`
`Combined oral contraceptives (OCs) are not recommended for women who are over 35 years old
`and smoke. Cigarette smoking increases the risk of serious cardiovascular side effects from OC
`use. The risk increases with age and with the number of cigarettes smoked.
`
`This product does not protect against infection from HIV (the virus that causes AIDS) or
`other sexually transmitted diseases.
`
`DESCRIPTION
`
`Supplied by manufacturer
`
`CLINICAL PHARMACOLOGY
`
`Mode of action
`
`OCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible
`mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial
`changes that reduce the likelihood of implantation.
`
`Receptor binding studies can be summarized briefly here if clinically relevant.
`
`Pharmacokinetics
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`Supplied by manufacturer, to include the following subsections:
`
` Absorption
` Distribution
` Metabolism
` Excretion
` Special Populations
` Renal and Hepatic Impairment
` Drug-drug Interactions (include mechanism for drug interaction for specific product, refer to
`PRECAUTIONS for class-labeling for OC products.)
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`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
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`Contains Nonbinding Recommendations
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`Draft — Not for Implementation
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`INDICATIONS AND USAGE
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`(Name of OC) is indicated for use by women to lower the risk of becoming pregnant.
`
`Other approved indications appear here.
`
`Pregnancy rates from clinical trials should be placed here.
`In clinical trials of (insert name of OC here), about (insert whole number here) out of 100
`women became pregnant during the first year of use. The effectiveness of any OC depends on
`correct and consistent use, and factors that affect ability to conceive, including age and frequency
`of intercourse.
`
`The following table shows estimates of the number of women who become pregnant during the
`first year of use, based mainly on clinical trial data, for various birth control methods.
`
`Approximate Percentage of Women Who Become Pregnant During the First Year of Use of a Birth Control Method*
`
`PREGNANCIES PER 100 WOMEN PER YEAR
`Fewer than 1
`
`METHOD
`estrogen/progestin injection
`levonorgestrel implants
`levonorgestrel IUD and copper IUD
`medroxyprogesterone acetate injection
`sterilization
`estrogen/progestin contraceptive products:
`
`pills
`
`skin patch
`
`vaginal ring
`progestin-only pills
`condom (male)
`diaphragm
`25 or more
`spermicides
`* The estimates for drugs, condoms, diaphragms, and IUDs are derived from clinical trial data reviewed by the Food
`and Drug Administration. The estimates for sterilization and spermicides come from the medical literature.
`
`1
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`2
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`Clinical Studies
`
`This section can contain a brief description of the extent of the Phase III program, such as the
`number of patients, the number of patients less than 35 years old, the number of treatment
`months. This section can also be used when there is an efficacy or safety issue specific to the
`product that is not addressed in class labeling. The location of this section may vary, depending
`on content.
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`Contains Nonbinding Recommendations
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`Draft — Not for Implementation
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`CONTRAINDICATIONS
`
`OCs should not be used by women who have the following conditions:
`
` Breast cancer or other hormone-sensitive cancer, now or in the past
` Liver tumors, now or in the past, or liver disease
` Undiagnosed abnormal genital bleeding
` Any condition predisposing to thrombotic diseases
` Thrombophlebitis or pulmonary embolism, now or in the past
` Cerebrovascular disease
` Coronary artery disease
` Thrombogenic valvular or thrombogenic rhythm diseases of the heart
` Congenital hypercoagulopathies
` Diabetes with vascular disease
` Uncontrolled hypertension
` Migraines with focal neurologic symptoms
` Smoking and over age 35
` Pregnancy
` Allergy to any components of this drug product
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`WARNINGS
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`The use of OCs with estrogen and progestin increases the risk of serious conditions, including
`myocardial infarction, thromboembolism, stroke, hepatic neoplasia, and gallbladder disease.
`However, the risk of serious morbidity or mortality is small in healthy women without
`underlying risk factors. When considering OCs for a woman with underlying risk factors, the
`risks of pregnancy and the feasibility of other birth control methods must also be considered.
`
`Minimizing exposure to estrogen and progestin reduces the risk of thrombotic events. For any
`particular estrogen/progestin combination, the recommended dosage regimen is that which
`contains the least amount of estrogen and progestin that is compatible with a low pregnancy rate
`and the medical needs of the individual patient.
`
`1.
`
`Vascular Risks
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`a. Mortality
`
`For nonsmokers, the risk of cardiovascular death from OC use is less than the risk of death from
`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 35.1
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`b. Thromboembolism
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`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 The risk
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`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
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`Contains Nonbinding Recommendations
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`Draft — Not for Implementation
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`of thromboembolic disease associated with OCs is not related to length of use and disappears after
`use of the drug product is stopped.2
`
`A 2- to 4-fold increase in relative risk of postoperative thromboembolic complications has been
`reported with the use of OCs.7 The relative risk of venous thrombosis in women who have
`predisposing conditions is twice that of women without such medical conditions.11 If feasible, OCs
`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
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`OCs should be started no earlier than 3 to 4 weeks after delivery in women who elect not to breast-
`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
`
`OCs are associated with retinal vein thrombosis in case reports. OCs should be discontinued if
`there is unexplained partial or complete loss of vision; onset of proptosis or diplopia, papilledema,
`or retinal vascular lesions. Symptoms of retinal vein thrombosis should be evaluated
`immediately.16,17,18
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`OC use may also increase the risk of thrombosis in women with valvular heart conditions19 or
`arrhythmias that predispose to thrombosis, such as atrial fibrillation.
`
`The presence of factor V Leiden mutation and other hereditary or acquired coagulation disorders
`increases the risk of thromboembolic disease.20
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`For desogestrel containing products: Several epidemiologic studies indicate that OCs containing
`desogestrel are associated with a higher risk of venous thromboembolism than OCs containing
`other progestins. In general, these studies indicate an approximate 2-fold increased risk, which
`corresponds to an additional 1 to 2 cases of venous thromboembolism per 10,000 women-years of
`use. However, data from other studies have not shown this 2-fold increase in risk.
`
`c. Myocardial infarction
`
`An increased risk of myocardial infarction is attributed to OC use. This risk is mainly in women
`with underlying risk factors for coronary artery disease such as smoking, hypertension,
`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 The risk is very low under
`the age of 30.
`
`Smoking in combination with OC use contributes substantially to the incidence of myocardial
`infarctions in women in their mid-30s or older, with smoking accounting for the majority of excess
`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
`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
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`Petitioner Exhibit 1020
`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
`Page 8
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`

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`Contains Nonbinding Recommendations
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`Draft — Not for Implementation
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`OCs must be used with caution in women with cardiovascular disease risk factors. OCs may further
`increase the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age,
`and obesity. 30
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`d. Cerebrovascular diseases
`
`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
`
`The relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14
`for users with severe hypertension.34 The relative risk of hemorrhagic stroke is reported to be 1.2
`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
`
`e. Dose-related risk of vascular disease from OCs
`
`A positive association has been observed between the amount of estrogen and progestin in OCs and
`the risk of vascular disease.35,36,37 A decline in serum high-density lipoproteins (HDL) is seen with
`many progestational agents.38,39,40
`
`2.
`
`Carcinoma of the Breast and Cervix
`
`Women who currently have or have had breast cancer should not use oral contraceptives because
`breast cancer may be hormonally sensitive.
`
`There is substantial evidence that OCs do not increase the incidence of breast cancer.41,42Although
`some past studies have suggested that OCs might increase the incidence of breast cancer, more
`recent and thoroughstudies have not confirmed such findings.
`
`Some studies suggest that OCs are associated with an increase in the risk of cervical cancer or
`intraepithelial neoplasia.43,44,45,46 However, there is controversy about the extent to which these
`findings are due to differences in sexual behavior and other factors.
`
`3.
`
`Liver Disease
`
`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 Rupture of benign, hepatic adenomas may
`cause death through intra-abdominal hemorrhage.48,49
`
`Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long-
`term (more than 8 years) OC users.50,51,52,53 However, the attributable risk (the excess incidence) of
`liver cancers in OC users is less than one per million users.
`
`OC-related cholestasis has been described in women with a history of pregnancy-related cholestasis.
`Women with a history of OC-related cholestasis may have the condition recur with subsequent OC
`use.54
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`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
`Page 9
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`

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`Contains Nonbinding Recommendations
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`Draft — Not for Implementation
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`OCs should be discontinued if jaundice develops. Steroid hormones may be poorly metabolized in
`patients with impaired liver function.
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`4.
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`Gallbladder Disease
`
`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
`
`5.
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`Carbohydrate and Lipid Metabolic Effects
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`OCs may decrease glucose tolerance in a dose-related fashion.62,63 Therefore, prediabetic and
`diabetic women should be carefully monitored while taking OCs. However, in nondiabetic women,
`OCs appear to have no effect on fasting blood glucose.64
`
`A small proportion of women will have adverse lipid changes while on OCs. Alternative
`contraception should be considered in women with uncontrolled dyslipidemias.65 Elevations of
`plasma triglycerides may lead to pancreatitis and other complications.
`
`6.
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`High Blood Pressure
`
`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 and this
`increase is more likely in older OC users70 and with extended duration of use. Data from the Royal
`College of General Practitioners71 and subsequent randomized trials have shown that the incidence
`of hypertension increases with increasing progestational activity and concentrations of progestins.
`If OCs are prescribed for women with well-controlled hypertension, close blood pressure
`monitoring is recommended and OCs should be discontinued if blood pressure rises significantly.
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`7.
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`Headache
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`The onset or exacerbation of migraine or development of headache with a new pattern that is
`recurrent, persistent, or severe requires discontinuation of OCs and evaluation of the cause.
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`8.
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`Vaginal Bleeding Problems
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`Breakthrough bleeding and spotting are sometimes seen in patients on OCs, especially during the
`first 3 months of use. If bleeding persists, nonhormonal causes such as pregnancy or malignancy
`should be considered. If pathology and pregnancy are excluded, time or a change to another
`formulation may solve the problem.
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`Amenorrhea is sometimes seen in women who are using OCs. Pregnancy should be ruled out in the
`event of amenorrhea.
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`A description of vaginal bleeding patterns from the controlled clinical trials that supported drug
`approval should be placed here if relevant.
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`Contains Nonbinding Recommendations
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`Draft — Not for Implementation
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`PRECAUTIONS
`
`1.
`
`General
`
`Women who are using oral contraceptives should have an annual history and physical
`examination, including special reference to blood pressure, breasts, abdomen and pelvic organs,
`as well as cervical cytology and relevant laboratory tests.
`
`2.
`
`Information for Patients
`
`See patient labeling.
`
`3.
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`Hypocalcemia
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`Estrogens should be used with caution in individuals with severe hypocalcemia because this
`condition may be aggravated.
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`4.
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`Drug Interactions
`
`Changes in contraceptive effectiveness associated with co-administration of other products:
`
`a. Anti-infective agents and anticonvulsants
`
`Contraceptive effectiveness may be reduced when hormonal contraceptives are co-administered
`with antibiotics, anticonvulsants, and other drugs that increase the metabolism of contraceptive
`steroids.72 This could result in unintended pregnancy or breakthrough bleeding. Some examples
`include rifampin, barbiturates, phenylbutazone, phenytoin, carbamezepine, felbamate,
`oxcarbazepine, topiramate, and griseofulvin.
`
`b. Anti-HIV protease inhibitors
`
`Several of the anti-HIV protease inhibitors have been studied with co-administration of oral
`combination hormonal contraceptives; significant changes (increase and decrease) in the plasma
`levels of the estrogen and progestin have been noted in some cases. The safety and efficacy of OC
`products may be affected with co-administration of anti-HIV protease inhibitors. Health care
`providers should refer to the label of the individual anti-HIV protease inhibitors for further drug-
`drug interaction information.
`
`c. Herbal products
`
`Herbal products containing St. John’s Wort (hypericum perforatum) may induce hepatic enzymes
`(cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of
`contraceptive steroids. This may also result in breakthrough bleeding.
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`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
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`Contains Nonbinding Recommendations
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`Draft — Not for Implementation
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`Increase in plasma levels of estradiol associated with co-administered drugs:
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`Co-administration of atorvastatin and certain OCs containing ethinyl estradiol increase AUC values
`for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma
`ethinyl estradiol levels, possibly by inhibition of conjugation. CYP 3A4 inhibitors such as
`itraconazole or ketoconazole may increase plasma hormone levels.
`
`Changes in plasma levels of co-administered drugs:
`
`Combination hormonal contraceptives containing some synthetic estrogens (e.g., ethinyl estradiol)
`may inhibit the metabolism of other compounds. Increased plasma concentrations of cyclosporin,
`prednisolone, and theophylline have been reported with concomitant administration of OCs.
`Decreased plasma concentrations of acetaminophen and increased clearance of temazepam, salicylic
`acid, morphine and clofibric acid, due to induction of conjugation have been noted when these
`drugs were administered with OCs.
`
`5.
`
`Interactions with Laboratory Tests
`
`Certain endocrine and liver function tests and blood components may be affected by OCs:
`
`a. Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased
`norepinephrine-induced platelet aggregability.
`
`b. Increased thyroid binding globulin (TBG) leading to increased circulating total thyroid
`hormone, as measured by protein-bound iodine (PBI), T4 by column or by
`radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG, free T4
`concentration is unaltered. Patients dependent on thyroid hormone replacement therapy who
`are also receiving estrogens may require increased doses of their thyroid replacement
`therapy.
`
`c. Other binding proteins may be elevated in serum.
`
`d. Sex hormone binding globulins are increased and result in elevated levels of total circulating
`sex steroids; however, free or biologically active levels either decrease or remain unchanged.
`
`e. Triglycerides may be increased and levels of various other lipids and lipoproteins may be
`affected.
`
`f. Glucose tolerance may be decreased.
`
`6.
`
`Carcinogenesis, Mutagenesis, Impairment of Fertility
`
`Carcinoma of the Breast
`See CONTRAINDICATIONS and WARNINGS (subsection 2.
`and Cervix). If the OC contains a new progestin or estrogen, data on animal carcinogenicity,
`mutagenicity, and return to fertility should be placed here.
`
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`9
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`Petitioner Exhibit 1020
`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
`Page 12
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`

`
`Contains Nonbinding Recommendations
`
`Draft — Not for Implementation
`
` 7.
`
`Pregnancy
`
`There appears to be little or no increased risk of birth defects in women who have used OCs
`inadvertently during early pregnancy.73,74However, if any component of the drug product is
`associated with birth defects, add a statement about the types of defects, estimated frequency, the
`associated doses, and the gestational age of exposure, if known.
`
`If the OC contains a new progestin or estrogen, a statement that summarizes what is known about
`pregnancy risk should be placed here, followed by a summary of the animal/human data.
`
`8.
`
`Nursing Mothers
`
`Small amounts of OC steroids have been identified in the milk of nursing mothers. In addition, OCs
`given in the postpartum period may interfere with lactation by decreasing the quantity and quality of
`breast milk. If possible, the nursing mother should be advised to use other forms of contraception
`until she has weaned her child.
`
`9.
`
`Pediatric Use
`
`Safety and efficacy are expected to be the same for postpubertal adolescents and adult women. OCs
`are not indicated before menarche.
`
`10.
`
`Geriatric Use
`
`OCs have not been studied in postmenopausal women and are not indicated in this population.
`
`ADVERSE EXPERIENCES
`
`The most serious adverse reactions associated with the use of OCs are in the WARNINGS and
`PRECAUTIONS sections.
`
`Other side effects commonly reported by OC users are:
`
` Nausea
` Breast tenderness
` Headaches
`
`The following adverse reactions may occur less frequently:
`
` Acne
` Decreased libido
` Dizziness
` Fluid retention
`
`Increased cervical ectopia
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`Petitioner Exhibit 1020
`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
`Page 13
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`

`
`Contains Nonbinding Recommendations
`
`Draft — Not for Implementation
`
` Melasma
` Mood changes and depression
` Ocular effects, including decreased tolerability to contact lenses
` Vaginal candidiasis
` Vomiting and other gastrointestinal symptoms (e.g., bloating)
` Weight changes
`
`It is not always clear whether these side effects are caused by OCs and, if so, whether the
`estrogen and/or the progestin is responsible. These side effects are most common in the first 1 to
`3 pill cycles.
`
`Manufacturers should add additional details regarding adverse experiences and cycle control
`unique to the product.
`
`POSSIBLE HEALTH BENEFITS
`
`Possible benefits associated with OC use beyond lowering of risk of becoming pregnant include the
`following effects on menses:
`
` More regular
` Less blood loss
` Less dysmenorrhea
`
`OVERDOSAGE
`
`There have been no reports of serious ill effects from overdose, including ingestion by children.
`Overdose may cause nausea and withdrawal bleeding.
`
`DOSAGE AND ADMINISTRATION
`
`To achieve maximum contraceptive effectiveness, OCs must be taken as directed. One tablet is
`taken at about the same time every day. Single missed pills should be taken as soon as
`remembered. For detailed instructions, see the patient labeling that is printed below.
`
`OCs may be started 3 to 4 weeks postpartum in women who do not breast feed. When OCs are
`used during the postpartum period, the increased risk of thromboembolic disease associated with
`the postpartum period must be considered.14 The possibility of ovulation and conception before
`starting OCs should also be considered.15
`
`418
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`I:\5197dft.doc
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`11
`
`Petitioner Exhibit 1020
`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
`Page 14
`
`

`
`Contains Nonbinding Recommendations
`
`Draft — Not for Implementation
`
`HOW SUPPLIED
`
`Manufacturer to provide information on available dosage forms, potency, color, and packaging.
`
`Manufacturer to include statement such as "Keep out of reach of children."
`
`STORAGE
`
`Manufacturer to provide information on pill storage.
`
`REFERENCES
`
`Supplied upon request.
`
`
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`I:\5197dft.doc
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`12
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`Petitioner Exhibit 1020
`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
`Page 15
`
`

`
`Contains Nonbinding Recommendations
`
`Draft — Not for Implementation
`
`III.
`
`PATIENT LABELING
`
`Guide for Using (OC name)
`
`WARNING TO WOMEN WHO SMOKE
`
`Do not use (OC name) if you smoke cigarettes and are over 35 years old. Smoking increases
`your risk of serious side effects from birth control pills, including death from heart attack, blood
`clots, or stroke. The risk increases with age and the number of cigarettes you smoke.
`
`Birth control pills help to lower the chances of becoming pregnant. They do not protect
`against HIV infection (AIDS) and other sexually transmitted diseases.
`
`WHAT IS (OC NAME)?
`
`(OC name) is a birth control pill. It contains two hormones, an estrogen called (name of
`estrogen), and a progestin called (name of progestin).
`
`HOW WELL DOES (OC NAME) WORK?
`
`Your chance of getting pregnant depends on how well you follow the directions for taking your
`birth control pills. The more carefully you follow the directions, the less chance you have of
`getting pregnant.
`
`In clinical studies, about (insert whole number here) out of 100 women got pregnant during the
`first year that they used (insert OC name here).
`
`The following table shows how the birth control pill compares with some other methods of birth
`control. The numbers are estimates of the number of women out of 100 women who become
`pregnant in 1 year of use.2
`
`470
`471
`472
`473
`
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`475
`476
`477
`478
`479
`480
`481
`482
`483
`
`484
`485
`486
`487
`488
`489
`490
`491
`492
`493
`