Cigarette smoking increases the risk of serious cardiovascular disease. Women who use oral contraceptives should be strongly advised not to smoke.
OVRETTE does not contain estrogen and, therefore, this insert does not discuss the serious health risks that have been associated with the estrogen component of combination oral contraceptives (COCs). The health-care professional is referred to the prescribing information of COCs for a discussion of those risks. The relationship between progestin-only oral contraceptives and these risks is not fully defined. The physician should remain alert to the earliest manifestation of symptoms of any serious disease and discontinue oral contraceptive therapy when appropriate.
- Ectopic Pregnancy
The incidence of ectopic pregnancies for progestin-only oral contraceptive users is 5 per 1000 woman-years. Up to 10% of pregnancies reported in clinical studies of progestin-only oral contraceptive users are extrauterine. Although symptoms of ectopic pregnancy should be watched for, a history of ectopic pregnancy need not be considered a contraindication to use of this contraceptive method. Health-care professionals should be alert to the possibility of an ectopic pregnancy in women who become pregnant or complain of lower abdominal pain while on progestin-only oral contraceptives.
- Delayed Follicular Atresia/Ovarian Cysts
If follicular development occurs, atresia of the follicle is sometimes delayed, and the follicle may continue to grow beyond the size it would attain in a normal cycle. Generally these enlarged follicles disappear spontaneously. Often they are asymptomatic; in some cases they are associated with mild abdominal pain. Rarely they may twist or rupture, requiring surgical intervention.
- Irregular Genital Bleeding
Irregular menstrual patterns are common among women using progestin-only oral contraceptives. If genital bleeding is suggestive of infection, malignancy, pregnancy, or other conditions, such nonpharmacologic causes should be ruled out. If prolonged amenorrhea occurs, the possibility of pregnancy should be evaluated. If one menstrual period is missed and the progestin-only oral contraceptive has not been taken according to directions, or if two consecutive periods are missed, tablet-taking should be discontinued and a nonhormonal back-up method of contraception should be used until the possibility of pregnancy is excluded.
- Carcinoma of the Breast and Reproductive Organs
Some epidemiological studies of oral contraceptive users have reported a slightly increased risk of having breast cancer diagnosed in women who were currently using combination oral contraceptives (COCs). The increased risk gradually disappeared within 10 years after stopping use of combination oral contraceptives. Breast cancers diagnosed in ever-users tend to be less clinically advanced than the cancers diagnosed in never-users. These studies have predominantly involved COCs and there are insufficient data to determine whether the use of progestin-only oral contraceptives similarly increases the risk. However, women with breast cancer should not use oral contraceptives because the role of female hormones in breast cancer has not been fully determined.
Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia or invasive cervical cancer in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.
There are insufficient data to determine whether the use of progestin-only oral contraceptives increases the risk of developing cervical intraepithelial neoplasia.
- Hepatic Neoplasia/Liver Disease
Benign hepatic adenomas are associated with COC use, although the incidence of benign tumors is rare in the United States. Rupture of benign, hepatic adenomas may cause death through intra-abdominal hemorrhage.
Studies from Britain and the US have shown an increased risk of developing hepatocellular carcinoma in COC-users. However, these cancers are rare. There are insufficient data to determine whether progestin-only oral contraceptives increase the risk of developing hepatic neoplasia.
Women with a history of oral contraceptive related cholestasis or women with cholestasis during pregnancy are more likely to have this condition with oral contraceptive use. If these women receive a progestin-only oral contraceptive they should be carefully monitored and, if the condition recurs, progestin-only oral contraceptive use should be discontinued.
- Thromboembolic Disorders and Other Vascular Problems
An increased risk of venous and arterial thrombotic and thromboembolic events have been found to be associated with the use of COCs. These events include superficial venous thrombosis, deep-vein thrombosis, pulmonary embolism, retinal vascular thrombosis, myocardial infarction, and cerebrovascular events (thrombotic and hemorrhagic strokes). There are insufficient data to determine whether the use of progestin-only contraceptives increases the risk of developing thrombotic disease and/or other vascular problems. However, there have been reports of some of these conditions coincident with the use of progestin-only oral contraceptives; therefore, the possibility of thrombosis should be considered.
Care should be used when prescribing progestin-only oral contraceptives to women predisposed to thromboembolic disorders (eg, a history of thromboembolic events, thrombophilia, cardiovascular disease; women who are obese or experience prolonged immobilization).
Patients should be counseled that oral contraceptives do not protect against transmission of HIV (AIDS) and other sexually transmitted diseases (STDs) such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis.
2. PHYSICAL EXAMINATION AND FOLLOW UP
A complete personal and family medical history and physical examination is appropriate for all women, including women using oral contraceptives. The physical examination may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. Such examinations should be repeated periodically during the use of progestin-only oral contraceptives.
3. CARBOHYDRATE AND LIPID EFFECTS
Some progestin-only oral contraceptive users may experience slight deterioration in glucose tolerance with increases in plasma insulin, but women with diabetes mellitus who use progestin-only oral contraceptives do not generally experience changes in their insulin requirements. Nonetheless, diabetic women should be carefully observed while taking progestin-only oral contraceptives.
Lipid metabolism is occasionally affected in that HDL, HDL2, and apolipoprotein A-I and A-II may be decreased; hepatic lipase may be increased. There is usually no effect on total cholesterol, HDL3, LDL, or VLDL.
4. DRUG INTERACTIONS
The effectiveness of progestin-only pills is reduced by hepatic enzyme-inducing drugs such as the anticonvulsants, phenytoin, carbamazepine; barbiturates; the antituberculosis drug rifampin; protease inhibitors; and herbal preparations containing St. John's Wort (hypericum perforatum). This could result in unintended pregnancy or breakthrough bleeding. There are anecdotal reports of reduced efficacy of combination oral contraceptives when used concomitantly with broad-spectrum antibiotics. No significant interaction has been found with progestin-only oral contraceptives and broad-spectrum antibiotics.
During concomitant use of OVRETTE and substances that may affect its efficacy, it is recommended that a nonhormonal back-up method of contraception be used in addition to the regular intake of OVRETTE. Use of a nonhormonal back-up method is advisable after discontinuation of substances that have led to induction of hepatic microsomal enzymes. It may take several weeks until enzyme induction has subsided, depending on dosage, duration of use, and rate of elimination of the inducing substance. For women receiving long-term therapy with hepatic enzyme inducers, another method of contraception should be considered.
Substances that reduce gastrointestinal transit time may affect contraceptive efficacy.
The product information of concomitant medications/substances should be consulted to identify potential interactions.
5. INTERACTIONS WITH LABORATORY TESTS
The following endocrine tests may be affected by progestin-only oral contraceptive use:
Sex hormone-binding globulin (SHBG) concentrations may be decreased.
Total thyroxine concentrations may be decreased, due to a decrease in thyroid binding globulin (TBG). However, free thyroxine level should remain unchanged.
See WARNINGS section.
Many epidemiological studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins. The few studies of infant growth and development that have been conducted have not demonstrated significant adverse effects. It is nonetheless prudent to rule out suspected pregnancy before initiating any hormonal contraceptive use. Epidemiological studies also do not suggest a teratogenic effect of oral contraceptives when taken inadvertently during early pregnancy. (See CONTRAINDICATIONS.)
8. NURSING MOTHERS
Small amounts of progestin pass into the breast milk, resulting in steroid levels in infant plasma. No adverse effects have been found on breastfeeding performance. Very rarely, adverse effects in the infant/child have been reported, including jaundice.
9. FERTILITY FOLLOWING DISCONTINUATION
The limited available data do not indicate a significant delay in the return of normal ovulation and fertility following discontinuation of progestin-only oral contraceptives.
The onset or exacerbation of migraine, or development of headache with a new pattern that is recurrent, persistent, or severe requires discontinuation of oral contraceptives and evaluation of the cause.
Women with migraine (particularly migraine with aura) who take progestin-only oral contraceptives may be at increased risk of stroke.
Diarrhea and/or vomiting may reduce hormone absorption.
12. PEDIATRIC USE
Safety and efficacy of OVRETTE has been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and users 16 and older. Use of this product before menarche is not indicated.
13. FD&C YELLOW NO. 5
This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. (See CONTRAINDICATIONS.)
14. GERIATRIC USE
This product has not been studied in women over 65 years of age and is not indicated in this population.
INFORMATION FOR THE PATIENT
See PATIENT LABELING for detailed information.
The following points should be discussed with prospective users before prescribing progestin-only oral contraceptives:
The necessity of taking pills at the same time every day, including throughout all bleeding episodes.
The need to use a nonhormonal back-up method of contraception (such as condoms and/or spermicides) for the next 48 hours whenever a progestin-only oral contraceptive is taken 3 or more hours late.
The potential side effects of progestin-only oral contraceptives, particularly menstrual irregularities.
The need to inform the clinician of prolonged episodes of bleeding, amenorrhea or severe abdominal pain.
The importance of using a barrier method in addition to progestin-only oral contraceptives if a woman is at risk of contracting or transmitting STDs/HIV.