Each Myzilra™ cycle of 28 tablets consists of three different drug phases as follows: Phase 1 comprised of 6 beige tablets, each containing 0.05 mg of levonorgestrel (d(-)-13 beta-ethyl-17-alpha-ethinyl-17-beta-hydroxygon-4-en-3-one), a totally synthetic progestogen, and 0.03 mg of ethinyl estradiol (19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3, 17-diol); phase 2 comprised of 5 white tablets, each containing 0.075 mg levonorgestrel and 0.04 mg ethinyl estradiol; and phase 3 comprised of 10 light-yellow tablets, each containing 0.125 mg levonorgestrel and 0.03 mg ethinyl estradiol; then followed by 7 light-green inert tablets. The inactive ingredients present are microcrystalline cellulose, FD&C Blue 2, FD&C Red 40, FD&C Yellow 6, D&C Yellow 10, hypromellose, iron oxide yellow, lactose monohydrate, magnesium stearate, polyethylene glycol, pregelatinized starch, and vitamin E.
CLINICAL PHARMACOLOGY
Combination oral contraceptives primarily act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation).
INDICATIONS AND USAGE
Oral contraceptives are indicated for the prevention of pregnancy in women who elect to use Myzilra™ Tablets as a method of contraception. Oral contraceptives are highly effective. TABLE I 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 and the IUD, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.
TABLE I: PERCENTAGE OF WOMEN EXPERIENCING AN UNINTENDED PREGNANCY DURING THE FIRST YEAR OF USE OF A CONTRACEPTIVE METHOD
|
| Method |
Perfect Use |
Typical Use |
| Levonorgestrel implants |
0.05 |
0.05 |
| Male sterilization |
0.1 |
0.15 |
| Female sterilization |
0.5 |
0.5 |
| Injectable progestogen |
0.3 |
0.3 |
| Oral contraceptives |
|
5 |
| Combined |
0.1 |
NA |
| Progestin only |
0.5 |
NA |
| IUD |
|
|
| Progesterone |
1.5 |
2.0 |
| Copper T 380A |
0.6 |
0.8 |
| Condom (male) without spermicide |
3 |
14 |
| (Female) without spermicide |
5 |
21 |
| Cervical cap |
|
|
| Nulliparous women |
9 |
20 |
| Parous women |
26 |
40 |
| Vaginal sponge |
|
|
| Nulliparous women |
9 |
20 |
| Parous women |
20 |
40 |
| Diaphragm with spermicidal cream or jelly |
6 |
20 |
Spermicides alone (foam, creams, jellies,
and vaginal suppositories) |
6 |
26 |
| Periodic abstinence (all methods) |
1 to 9 |
25 |
| Withdrawal |
4 |
19 |
| No contraception (planned pregnancy) |
85 |
85 |
| NA - not available |
Adapted from Hatcher RA et al, Contraceptive Technology: 17th Revised Edition. NY, NY: Ardent Media, Inc., 1998.
CONTRAINDICATIONS
Oral contraceptives should not be used in women with any of the following conditions:
Thrombophlebitis or thromboembolic disorders.
A past history of deep-vein thrombophlebitis or thromboembolic disorders.
Cerebral-vascular or coronary-artery disease.
Known or suspected carcinoma of the breast.
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.
WARNINGS
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.
The use of oral contraceptives is associated with increased risks of several serious conditions including myocardial infarction, thromboembolism, stroke, hepatic neoplasia, gallbladder disease, and hypertension, 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 based principally 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 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.
1. Thromboembolic Disorders and Other Vascular Problems
a. Myocardial InfarctionAn 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 (TABLE II) among women who use oral contraceptives.
CIRCULATORY DISEASE MORTALITY RATES PER 100,000 WOMAN YEARS BY AGE, SMOKING STATUS AND ORAL-CONTRACEPTIVE USE
| |
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 9 in WARNINGS). Similar effects on risk factors have been associated with an increased risk of heart disease. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors.
b. ThromboembolismAn increased risk of venous 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 nonusers 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 breast-feed, or a midtrimester pregnancy termination.
c. Cerebrovascular DiseasesOral contraceptives have been shown to increase both the relative and attributable risks 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 nonusers, 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 ContraceptivesA 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 progestogen 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 preparations containing less than 50 mcg of estrogen.
e. Persistence of Risk of Vascular DiseaseThere are two studies which have shown persistence of risk of vascular disease for ever-users of oral contraceptives. In a study in the United States, the risk of developing myocardial infarction after discontinuing oral contraceptives persists for at least 9 years for women 40 to 49 years who had used oral contraceptives for five or more years, but this increased risk was not demonstrated in other age groups. In another study in Great Britain, the risk of developing cerebrovascular disease persisted for at least 6 years after discontinuation of oral contraceptives, although excess risk was very small. However, both studies were performed with oral-contraceptive formulations containing 50 micrograms or higher of estrogens.
2. Estimates of Mortality From Contraceptive Use
One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (TABLE III). These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risks. The study concluded that with the exception of oral-contraceptive users 35 and older who smoke and 40 and older who do not smoke, mortality associated with all methods of birth control is less than that associated with childbirth. The observation of a possible increase in risk of mortality with age for oral-contraceptive users is based on data gathered in the 1970’s — but not reported until 1983. However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral-contraceptive use to women who do not have the various risk factors listed in this labeling.
Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed, the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular-disease risks may be increased with oral-contraceptive use after age 40 in healthy nonsmoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception.
Therefore, the Committee recommended that the benefits of oral-contraceptive use by healthy nonsmoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective.
TABLE III—ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NONSTERILE WOMEN, BY FERTILITY-CONTROL METHOD ACCORDING TO AGE
|
| Method of control and outcome |
15 to 19 |
20 to 24 |
25 to 29 |
30 to 34 |
35 to 39 |
40 to 44 |
| No fertility control methods |
7.0 |
7.4 |
9.1 |
14.8 |
25.7 |
28.2 |
Oral contraceptives
nonsmoker
|
0.3 |
0.5 |
0.9 |
1.9 |
13.8 |
31.6 |
Oral contraceptives
smoker†
|
2.2 |
3.4 |
6.6 |
13.5 |
51.1 |
117.2 |
| IUD† |
0.8 |
0.8 |
1.0 |
1.0 |
1.4 |
1.4 |
| Condom* |
1.1 |
1.6 |
0.7 |
0.2 |
0.3 |
0.4 |
| Diaphragm/spermicide* |
1.9 |
1.2 |
1.2 |
1.3 |
2.2 |
2.8 |
| Periodic abstinence* |
2.5 |
1.6 |
1.6 |
1.7 |
2.9 |
3.6 |
Adapted from H.W. Ory, Family Planning Perspectives, 15:57-63, 1983.
3. Carcinoma of the Reproductive Organs
Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian, and cervical cancer in women using oral contraceptives. The overwhelming evidence in the literature suggests that use of oral contraceptives is not associated with an increase in the risk of developing breast cancer, regardless of the age and parity, of first use or with most of the marketed brands and doses. The Cancer and Steroid Hormone (CASH) study also showed no latent effect on the risk of breast cancer for at least a decade following long-term use. A few studies have shown a slightly increased relative risk of developing breast cancer, although the methodology of these studies, which included differences in examination of users and nonusers and differences in age at start of use has been questioned.
Some studies suggest that oral-contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia 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.
In spite of many studies of the relationship between oral-contraceptive use and breast and cervical cancers, a cause-and-effect relationship has not been established.
4. Hepatic Neoplasia
Benign hepatic adenomas are associated with oral-contraceptive use, although the incidence of benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases/100,000 for users, a risk that increases after four or more years of use. Rupture of rare, benign, hepatic adenomas may cause death through intra-abdominal hemorrhage.
Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) oral-contraceptive users. However, these cancers are extremely rare in the U.S., and the attributable risk (the excess incidence) of liver cancers in oral-contraceptive users approaches less than one per million users.
5. Ocular Lesions
There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately.
6. Oral-Contraceptive Use Before or During Early Pregnancy
Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly insofar as cardiac anomalies and limb-reduction defects are concerned, when taken inadvertently during early pregnancy.
The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. Oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion.
It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral-contraceptive use. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period. Oral-contraceptive use should be discontinued if pregnancy is confirmed.
7. Gallbladder Disease
Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens. More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral-contraceptive users may be minimal. The recent findings of minimal risk may be related to the use of oral-contraceptive formulations containing lower hormonal doses of estrogens and progestogens.
8. Carbohydrate and Lipid Metabolic Effects
Oral contraceptives have been shown to cause glucose intolerance in a significant percentage of users. Oral contraceptives containing greater than 75 micrograms of estrogens cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance. Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents. However, in the nondiabetic woman, oral contraceptives appear to have no effect on fasting blood glucose. Because of these demonstrated effects, prediabetic and diabetic women should be carefully observed while taking oral contraceptives.
A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier (see WARNINGS, 1a. and 1d.), changes in serum triglycerides and lipoprotein levels have been reported in oral-contraceptive users.
9. Elevated Blood Pressure
An increase in blood pressure has been reported in women taking oral contraceptives, and this increase is more likely in older oral-contraceptive users and with continued use. Data from the Royal College of General Practitioners and subsequent randomized trials have shown that the incidence of hypertension increases with increasing quantities of progestogens.
Women with a history of hypertension or hypertension-related diseases, or renal disease, should be encouraged to use another method of contraception. If women with hypertension elect to use oral contraceptives, they should be monitored closely, and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued. For most women, elevated blood pressure will return to normal after stopping oral contraceptives, and there is no difference in the occurrence of hypertension among ever- and never-users.
10. Headache
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.
11. Bleeding Irregularities
Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use. The type and dose of progestogen may be important. Nonhormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out.
Some women may encounter post-pill amenorrhea or oligomenorrhea, especially when such a condition was preexistent.
PRECAUTIONSPatients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
1. Physical Examination and Follow-Up
A periodic history and physical examination is appropriate for all women, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent, or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care.
2. Lipid Disorders
Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult (see WARNINGS, 1d.).
3. Liver Function
If jaundice develops in any woman receiving such drugs, the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function.
4. Fluid Retention
Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention.
5. Emotional Disorders
Patients becoming significantly depressed while taking oral contraceptives should stop the medication and use an alternate method of contraception in an attempt to determine whether the symptom is drug related. Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree.
6. Contact Lenses
Contact-lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.
7. Drug Interactions
Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin. A similar association, though less marked, has been suggested with barbiturates, phenylbutazone, phenytoin sodium, and possibly with griseofulvin, ampicillin, and tetracyclines.
8. Interactions With Laboratory Tests
Certain endocrine- and liver-function tests and blood components may be affected by oral contraceptives:
- Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability.
- 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.
- Other binding proteins may be elevated in serum.
- Sex-binding globulins are increased and result in elevated levels of total circulating sex steroids and corticoids; however, free or biologically active levels remain unchanged.
- Triglycerides may be increased.
- Glucose tolerance may be decreased.
- Serum folate levels may be depressed by oral-contraceptive therapy. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives.
9. Carcinogenesis
See WARNINGS.
10. Pregnancy
Teratogenic Effects
Pregnancy category X
See CONTRAINDICATIONS and WARNINGS.
11. Nursing Mothers
Small amounts of oral-contraceptive steroids have been identified in the milk of nursing mothers, and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, oral contraceptives 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 not to use combination oral contraceptives but to use other forms of contraception until she has completely weaned her child.
12. Pediatric Use
Safety and efficacy of Myzilra™ Tablets—triphasic regimen have 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.
INFORMATION FOR THE PATIENT
See Patient Labeling printed below.
ADVERSE REACTIONS
An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS).
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 pain, 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, secretion.
Change in weight (increase or decrease).
Change in cervical erosion and secretion.
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:
Congenital anomalies.
Premenstrual syndrome.
Cataracts.
Optic neuritis.
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.
Sickle-cell disease.
Cerebral-vascular disease with mitral valve prolapse.
Lupus-like syndromes.
OVERDOSAGE
Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females.
NON-CONTRACEPTIVE HEALTH BENEFITS
The following non-contraceptive health benefits related to the use of oral contraceptives are supported by epidemiological studies which largely utilized oral-contraceptive formulations containing doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg of mestranol.
Effects on menses:
Increased menstrual cycle regularity.
Decreased blood loss and decreased incidence of iron-deficiency anemia.
Decreased incidence of dysmenorrhea.
Effects related to inhibition of ovulation:
Decreased incidence of functional ovarian cysts.
Decreased incidence of ectopic pregnancies.
Effects from long-term use:
Decreased incidence of fibroadenomas and fibrocystic disease of the breast.
Decreased incidence of acute pelvic inflammatory disease.
Decreased incidence of endometrial cancer.
Decreased incidence of ovarian cancer.
DOSAGE AND ADMINISTRATION
To achieve maximum contraceptive effectiveness, Myzilra™ Tablets—triphasic regimen must be taken exactly as directed and at intervals not exceeding 24 hours.
Myzilra™ Tablets are a three-phase preparation plus 7 inert tablets. The dosage of Myzilra™ Tablets is one tablet daily for 28 consecutive days per menstrual cycle in the following order: 6 beige tablets (phase 1), followed by 5 white tablets (phase 2), followed by 10 light-yellow tablets (phase 3), plus 7 light-green inert tablets, according to the prescribed schedule.
It is recommended that Myzilra™ Tablets be taken at the same time each day, preferably after the evening meal or at bedtime. During the first cycle of medication, the patient should be instructed to take one Myzilra™ Tablet daily in the order of 6 beige, 5 white, 10 light-yellow tablets, and then 7 light-green inert tablets for twenty-eight (28) consecutive days, beginning on day one (1) of her menstrual cycle. (The first day of menstruation is day one.) Withdrawal bleeding usually occurs within 3 days following the last light-yellow tablet. (If Myzilra™ Tablets are first taken later than the first day of the first menstrual cycle of medication or postpartum, contraceptive reliance should not be placed on Myzilra™ Tablets until after the first 7 consecutive days of administration. The possibility of ovulation and conception prior to initiation of medication should be considered.)
When switching from another oral contraceptive, Myzilra™ Tablets should be started on the first day of bleeding following the last active tablet taken of the previous oral contraceptive.
The patient begins her next and all subsequent 28 day courses of Myzilra™ Tablets on the same day of the week that she began her first course, following the same schedule. She begins taking her beige tablets on the next day after ingestion of the last light-green tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Any time a subsequent cycle of Myzilra™ Tablets is started later than the next day, the patient should be protected by another means of contraception until she has taken a tablet daily for seven consecutive days.
If spotting or breakthrough bleeding occurs, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her physician. Although the occurrence of pregnancy is highly unlikely if Myzilra™ Tablets are taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken before the medication is resumed. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.
The risk of pregnancy increases with each active (beige, white, or light-yellow) tablet missed. For additional patient instructions regarding missed pills, see the “WHAT TO DO IF YOU MISS PILLS” section in the DETAILED PATIENT LABELING below. If breakthrough bleeding occurs following missed active tablets, it will usually be transient and of no consequence. If the patient misses one or more light-green tablets, she is still protected against pregnancy provided she begins taking beige tablets again on the proper day.
In the nonlactating mother, Myzilra™ Tablets may be initiated postpartum, for contraception. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS concerning thromboembolic disease). It is to be noted that early resumption of ovulation may occur if bromocriptine mesylate has been used for the prevention of lactation.
HOW SUPPLIED
Myzilra™ (levonorgestrel and ethinyl estradiol tablets USP)—triphasic regimen is packaged in cartons of 3 and 6 blister pack tablet dispensers. Each blister pack tablet dispenser contains 28 round, film coated tablets as follows:
Six beige tablets debossed “93” on one side and “680” on the other side, each containing 0.05 mg levonorgestrel and 0.03 mg ethinyl estradiol;
five white tablets debossed “93” on one side and “681” on the other side, each containing 0.075 mg levonorgestrel and 0.04 mg ethinyl estradiol;
ten light-yellow tablets debossed “93” on one side and “682” on the other side, each containing 0.125 mg levonorgestrel and 0.03 mg ethinyl estradiol; and
seven light-green inert tablets debossed “93” on one side and “743” on the other side.
Blister pack tablet dispenser NDC 0603-7625-01
Boxes of 3 blister pack tablet dispensers NDC 0603-7625-49
Boxes of 6 blister pack tablet dispensers NDC 0603-7625-17
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Avoid humid conditions and protect from light by storing tablet blister in the cardboard sleeve provided.
References available upon request.
Manufactured In Canada By:
Patheon Inc.
Ontario, Canada L5N 7K9
Manufactured For:
QUALITEST PHARMACEUTICALS USA
Huntsville, AL 35811
Rev. 8/2011
BRIEF SUMMARY PATIENT PACKAGE INSERT
Rx only
Myzilra™ Tablets (like all oral contraceptives) are intended to prevent pregnancy. They do not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Oral contraceptives, also known as “birth-control pills” or “the pill,” are taken to prevent pregnancy, and when taken correctly, have a failure rate of less than 1.0% per year when used without missing any pills. The typical failure rate of large numbers of pill users is less than 3.0% per year when women who miss pills are included. For most women oral contraceptives are also free of serious or unpleasant side effects. However, forgetting to take pills considerably increases the chances of pregnancy.
For the majority of women, oral contraceptives can be taken safely. But there are some women who are at high risk of developing certain serious diseases that can be life-threatening or may cause temporary or permanent disability or death. The risks associated with taking oral contraceptives increase significantly if you:
- smoke.
- have high blood pressure, diabetes, high cholesterol.
- have or have had clotting disorders, heart attack, stroke, angina pectoris, cancer of the breast or sex organs, jaundice, or malignant or benign liver tumors.
You should not take the pill if you suspect you are pregnant or have unexplained vaginal bleeding.
Cigarette smoking increases the risk of serious adverse effects on the heart and blood vessels from oral-contraceptive use. This risk increases with age and with the 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 not smoke.
Most side effects of the pill are not serious. The most common such effects are nausea, vomiting, bleeding between menstrual periods, weight gain, breast tenderness, and difficulty wearing contact lenses. These side effects, especially nausea and vomiting, may subside within the first three months of use.
The serious side effects of the pill occur very infrequently, especially if you are in good health and do not smoke. However, you should know that the following medical conditions have been associated with or made worse by the pill:
1. Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), stoppage or rupture of a blood vessel in the brain (stroke), blockage of blood vessels in the heart (heart attack and angina pectoris) or other organs of the body. As mentioned above, smoking increases the risk of heart attacks and strokes and subsequent serious medical consequences.
2. Liver tumors, which may rupture and cause severe bleeding. A possible but not definite association has been found with the pill and liver cancer. However, liver cancers are extremely rare. The chance of developing liver cancer from using the pill is thus even rarer.
3. High blood pressure, although blood pressure usually returns to normal when the pill is stopped.
The symptoms associated with these serious side effects are discussed in the detailed leaflet given to you with your supply of pills. Notify your doctor or health-care provider if you notice any unusual physical disturbances while taking the pill. In addition, drugs such as rifampin, as well as some anticonvulsants and some antibiotics, may decrease oral-contraceptive effectiveness.
Studies to date of women taking the pill have not shown an increase in the incidence of cancer of the breast or cervix. There is, however, insufficient evidence to rule out the possibility that pills may cause such cancers.
Taking the pill provides some important non-contraceptive benefits. These include less pain
