Oral contraceptives are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. Oral contraceptives are highly effective. Table 1 lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used.
Correct and consistent use of methods can result in lower failure rates. TABLE 1: LOWEST EXPECTED AND TYPICAL FAILURE RATES DURING THE FIRST YEAR OF CONTINUOUS USE OF A METHOD % of Women Experiencing an Accidental Pregnancy in the First Year of Continuous Use Method Lowest Expected a Typical b (No contraception) (85) (85) Oral contraceptives combined 0.1 3 c progestin only 0.5 3 c Diaphragm with spermicidal cream or jelly 6 18 Spermicides alone (foam, creams, jellies and vaginal suppositories) 3 21 Vaginal sponge nulliparous 6 18 multiparous 9 28 IUD 0.8 to 2 3 d Condom without spermicides 2 12 Periodic abstinence (all methods) 1 to 9 20 Injectable progestogen 0.3 to 0.4 0.3 to
0.4Implants
6 capsules 0.04 0.04 2 rods 0.03
0.03 Female sterilization 0.2
0.4 Male sterilization 0.1
0.15Reproduced
with permission of the Population Council from J. Trussell, et. al: Contraceptive failure in the United States: An update. Studies in Family Planning, 21(1), January-February 1990. a) The authors’ best guess of the percentage of women expected to experience an accidental pregnancy among couples who initiate a method (not necessarily for the first time) and who use it consistently and correctly during the first year if they do not stop for any reason other than pregnancy. b) This term represents “typical” couples who initiate use of a method (not necessarily for the first time), who experience an accidental pregnancy during the first year if they do not stop use for any reason other than pregnancy. c) Combined typical rate for both combined and progestin only. d) Combined typical rate for both medicated and nonmedicated IUD.
Contraindications
Balziva is contraindicated in females who are known to have or develop the following conditions: Thrombophlebitis or thromboembolic disorders A past history of deep vein thrombophlebitis or thromboembolic disorders Cerebrovascular or coronary artery disease Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia Undiagnosed abnormal genital bleeding Cholestatic jaundice of pregnancy or jaundice with prior pill use Hepatic adenomas or carcinomas Known or suspected pregnancy Are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment).
The use of oral contraceptives is associated with increased risk of several serious conditions including myocardial infarction, thromboembolism, stroke, hepatic neoplasia, and gallbladder disease, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as hypertension, hyperlipidemias, obesity and diabetes.
Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks. The information contained in this package insert is principally based on studies carried out in patients who used oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined.
Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers.
The attributable risk does provide information about the actual occurrence of a disease in the population*. For further information, the reader is referred to a text on epidemiological methods. *Adapted from Stadel BB: Oral contraceptives and cardiovascular disease. N Engl J Med , 1981; 305: 612-618, 672-677; with author’s permission. Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use.
This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke. 1. Thromboembolic Disorders and Other Vascular Problems The physician should be alert to the earliest manifestations of thromboembolic thrombotic disorders as discussed below. Should any of these occur or be suspected the drug should be discontinued immediately. a.
Myocardial Infarction An increased risk of myocardial infarction has been attributed to oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current oral contraceptive users has been estimated to be two to six. The risk is very low under the age of 30.
Smoking in combination with oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid-thirties or older, with smoking accounting for the majority of excess cases. Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and nonsmokers over the age of 40 ( Figure 1 ) among women who use oral contraceptives.
FIGURE 1: CIRCULATORY DISEASE MORTALITY RATES PER 100,000 WOMAN-YEARS BY AGE, SMOKING STATUS AND ORAL CONTRACEPTIVE USE 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. Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age and obesity.
In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism. Oral contraceptives have been shown to increase blood pressure among users (see section 10 in WARNINGS ). Such increases in risk factors have been associated with an increased risk of heart disease and the risk increases with the number of risk factors present. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors.
Figure 1: Circulatory Disease Mortality Rates per 100,000 Women-Years by Age, Smoking Status and Oral Contraceptive Use b. Thromboembolism An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established. Case control studies have found the relative risk of users compared to non-users to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease.
Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalization. The risk of thromboembolic disease due to oral contraceptives is not related to length of use and disappears after pill use is stopped. A two- to four-fold increase in relative risk of postoperative thromboembolic complications has been reported with the use of oral contraceptives.
The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions. If feasible, oral contraceptives should be discontinued at least four weeks prior to and for two weeks after elective surgery of a type associated with an increase in risk of thromboembolism and during and following prolonged immobilization. Since the immediate postpartum period is also associated with an increased risk of thromboembolism, oral contraceptives should be started no earlier than four to six weeks after delivery in women who elect not to breastfeed. c.
Cerebrovascular Diseases Oral contraceptives have been shown to increase both the relative and attributable risk of cerebrovascular events (thrombotic and hemorrhagic strokes); although, in general, the risk is greatest among older (>35 years), hypertensive women who also smoke. Hypertension was found to be a risk factor for both users and non-users, for both types of strokes, while smoking interacted to increase the risk for hemorrhagic strokes.
In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension. The relative risk of hemorrhagic stroke is reported to be 1.2 for nonsmokers who used oral contraceptives, 2.6 for smokers who did not use oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users and 25.7 for users with severe hypertension.
The attributable risk is also greater in older women. d. Dose-Related Risk of Vascular Disease from Oral Contraceptives A positive association has been observed between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease. A decline in serum high density lipoproteins (HDL) has been reported with many progestational agents. A decline in serum high density lipoproteins has been associated with an increased incidence of ischemic heart disease.
Because estrogens increase HDL cholesterol, the net effect of an oral contraceptive depends on a balance achieved between doses of estrogen and progestogen and the nature and absolute amount of progestogens used in the contraceptive. The amount of both hormones should be considered in the choice of an oral contraceptive. Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics.
For any particular estrogen/progestogen combination, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and the needs of the individual patient. New acceptors of oral contraceptive agents should be started on prepara
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Pregnancy and breastfeeding
11. Pregnancy Teratogenic Effects Pregnancy Category X See CONTRAINDICATIONS and WARNINGS sections.
Adverse reactions
Post Marketing Experience: Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 ( Figure 2 ). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs ( Figure 2 ).
One of these studies reported no association between breast cancer risk and COC use. The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use. FIGURE 2: RISK OF BREAST CANCER WITH COMBINED ORAL CONTRACEPTIVE USE RR = relative risk; OR = odds ratio; HR = hazard ratio. “ever COC” are females with current or past COC use; “never COC use” are females that never used COCs.
An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section): Thrombophlebitis Arterial thromboembolism Pulmonary embolism Myocardial infarction Cerebral hemorrhage Cerebral thrombosis Hypertension Gallbladder disease Hepatic adenomas or benign liver tumors There is evidence of an association between the following conditions and the use of oral contraceptives, although additional confirmatory studies are needed: Mesenteric thrombosis Retinal thrombosis The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related: Nausea Vomiting Gastrointestinal symptoms (such as abdominal cramps and bloating) Breakthrough bleeding Spotting Change in menstrual flow Amenorrhea Temporary infertility after discontinuation of treatment Edema Melasma which may persist Breast changes: tenderness, enlargement, and secretion Change in weight (increase or decrease) Change in cervical ectropion and secretion Possible diminution in lactation when given immediately postpartum Cholestatic jaundice Migraine Rash (allergic) Mental depression Reduced tolerance to carbohydrates Vaginal candidiasis Change in corneal curvature (steepening) Intolerance to contact lenses The following adverse reactions have been reported in users of oral contraceptives, and the association has been neither confirmed nor refuted: Premenstrual syndrome Cataracts Changes in appetite Cystitis-like syndrome Headache Nervousness Dizziness Hirsutism Loss of scalp hair Erythema multiforme Erythema nodosum Hemorrhagic eruption Vaginitis Porphyria Impaired renal function Hemolytic uremic syndrome Budd-Chiari syndrome Acne Changes in libido Colitis 1
Composition
Active ingredients
ETHINYL ESTRADIOL 0.035MG; NORETHINDRONE 0.4MG
Official product information
Drugs@FDA lists the approved labels, letters and reviews for application ANDA076238.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
