Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 01 September 2017

Indication(s)

INDICATIONS AND USAGE 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 II 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 II: PERCENTAGE OF WOMEN EXPERIENCING AN UNINTENDED PREGNANCY DURING THE FIRST YEAR OF USE OF A CONTRACEPTIVE METHOD Method Perfect Use Typical Use NA - not available Adapted from Hatcher RA et al, Contraceptive Technology: 17th Revised Edition. NY, NY: Ardent Media, Inc., 1998 Levonorgestrel implants 0.05 0.05 Male sterilization 0.1 0.15 Female sterilization 0.5 0.5 Depo-Provera® (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) 1-9Depending on method (calendar, ovulation, symptothermal, post-ovulation) 25 Withdrawal 4 19 No contraception (planned pregnancy) 85 85

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Advisory information

contraindications
CONTRAINDICATIONS Combination 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. Thrombogenic valvulopathies. Thrombogenic rhythm disorders. Diabetes with vascular involvement. Uncontrolled hypertension. 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, or active liver disease, as long as liver function has not returned to normal. Known or suspected pregnancy. Hypersensitivity to any of the components of Trivora (levonorgestrel and ethinyl estradiol tablets–triphasic regimen). 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)
Special warnings and precautions
PRECAUTIONS 1. General Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases. 2. Physical Examination And Follow-Up A periodic personal and family medical history and complete physical examination are 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. 3. 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. ) In patients with familial defects of lipoprotein metabolism receiving estrogen-containing preparations, there have been case reports of significant elevations of plasma triglycerides leading to pancreatitis. 4. 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. 5. 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. 6. 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. 7. Contact Lenses Contact-lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist. 8. Gastrointestinal Motility Diarrhea and/or vomiting may reduce hormone absorption. 9. Drug Interactions Interactions between ethinyl estradiol and other substances may lead to decreased or increased serum ethinyl estradiol concentrations. Decreased ethinyl estradiol plasma concentrations may cause an increased incidence of breakthrough bleeding and menstrual irregularities and may possibly reduce efficacy of the combination oral contraceptive. Reduced ethinyl estradiol concentrations have been associated with concomitant use of substances that induce hepatic microsomal enzymes, such as rifampin, rifabutin, barbiturates, phenylbutazone, phenytoin sodium, griseofulvin, topiramate, some protease inhibitors, modafinil, and possibly St. John's wort. Substances that may decrease plasma ethinyl estradiol concentrations by other mechanisms include any substance that reduces gut transit time and certain antibiotics (e.g. ampicillin and other penicillins, tetracyclines) by a decrease of enterohepatic circulation of estrogens. During concomitant use of ethinyl estradiol containing products and substances that may lead to decreased plasma steroid hormone concentrations, it is recommended that a nonhormonal back-up method of birth control be used in addition to the regular intake of Trivora (levonorgestrel and ethinyl estradiol tablets-triphasic regimen). If the use of a substance which leads to decreased ethinyl estradiol plasma concentrations is required for a prolonged period of time, combination oral contraceptives should not be considered the primary contraceptive. After discontinuation of substances that may lead to decreased ethinyl estradiol plasma concentrations, use of a nonhormonal back-up method of birth control is recommended for 7 days. Longer use of a back-up method is advisable after discontinuation of substances that have led to induction of hepatic microsomal enzymes, resulting in decreased ethinyl estradiol concentrations. It may take several weeks until enzyme induction has completely subsided, depending on dosage, duration of use, and rate of elimination of the inducing substance. Some substances may increase plasma ethinyl estradiol concentrations. These include: Competitive inhibitors for sulfation of ethinyl estradiol in the gastrointestinal wall, such as ascorbic acid (vitamin C) and acetaminophen. Substances that inhibit cytochrome P450 3A4 isoenzymes such as indinavir, fluconazole, and troleandomycin. Troleandomycin may increase the risk of intrahepatic cholestasis during coadministration with combination oral contraceptives. Atorvastatin (unknown mechanism). Ethinyl estradiol may interfere with the mechanism of other drugs by inhibiting hepatic microsomal enzymes or by inducing hepatic drug conjugation, particularly glucuronidation. Accordingly, tissue concentrations may be either increased (e.g. cyclosporine, theophylline, corticosteroids) or decreased. The prescribing information of concomitant medications should be consulted to identify potential interactions. Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer Trivora with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see Warnings RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT). 10. 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. 11. Carcinogenesis See " WARNINGS " section. 12. Pregnancy Pregnancy Category X See " CONTRAINDICATIONS " and " WARNINGS " sections. 13. Nursing Mothers Small amounts of oral-contraceptive steroids and/or metabolites 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, combination 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. 14. Pediatric Use Safety and efficacy of Trivora (levonorgestrel and ethinyl estradiol 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.
Adverse reactions
ADVERSE REACTIONS An increased risk of the following serious adverse reactions (see " WARNINGS " section for additional information) has been associated with the use of oral contraceptives. Thromboembolic disorders and other vascular problems (including thrombophlebitis, arterial thromboembolism, pulmonary embolism, myocardial infarction, cerebral hemorrhage, cerebral thrombosis), carcinoma of the reproductive organs, hepatic neoplasia (including hepatic adenomas or benign liver tumors), ocular lesions (including retinal vascular thrombosis), gallbladder disease, carbohydrate and lipid effects, elevated blood pressure, and headache. 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/fluid retention. Melasma/chloasma which may persist. Breast changes: tenderness, pain, enlargement, secretion. Change in weight or appetite (increase or decrease). Change in cervical erosion and secretion. Diminution in lactation when given immediately postpartum. Cholestatic jaundice. Rash (allergic). Mood changes, including depression. Vaginitis, including candidiasis. Change in corneal curvature (steepening). Intolerance to contact lenses. Mesenteric thrombosis. Decrease in serum folate levels. Exacerbation of systemic lupus erythematosus. Exacerbation of porphyria. Exacerbation of chorea. Aggravation of varicose veins. Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms. 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, which may lead to partial or complete loss of vision. Cystitis-like syndrome. Nervousness. Dizziness. Hirsutism. Loss of scalp hair. Erythema multiforme. Erythema nodosum. Hemorrhagic eruption. 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. Pancreatitis. Dysmenorrhea.

Usage information

Dosing and administration
DOSAGE AND ADMINISTRATION To achieve maximum contraceptive effectiveness, Trivora® Tablets (levonorgestrel and ethinyl estradiol tablets—triphasic regimen) must be taken exactly as directed and at intervals not exceeding 24 hours. Trivora Tablets are a three-phase preparation plus 7 inert tablets. The dosage of Trivora Tablets is one tablet daily for 28 consecutive days per menstrual cycle in the following order: 6 blue tablets (phase 1), followed by 5 white tablets (phase 2), followed by 10 pink tablets (phase 3), plus 7 peach inert tablets, according to the prescribed schedule. It is recommended that Trivora 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 Trivora Tablet daily in the order of 6 blue, 5 white, 10 pink tablets, and then 7 peach 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 pink tablet and may not have finished before the next pack is started. (If Trivora 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 Trivora Tablets until after the first 7 consecutive days of administration and a nonhormonal back-up method of birth control should be used during those 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.) When switching from another oral contraceptive, Trivora Tablets should be started on the first day of bleeding following the last active tablet taken of the previous oral contraceptive. The patient may switch any day from a progestin-only pill and should begin Trivora the next day. If switching from an implant or injection, the patient should start Trivora on the day of implant removal or, if using an injection, the day the next injection would be due. In switching from a progestin-only pill, injection, or implant, the patient should be advised to use a non-hormonal back-up method of birth control for the first 7 days of tablet-taking. The patient begins her next and all subsequent 28-day courses of Trivora Tablets on the same day of the week that she began her first course, following the same schedule. She begins taking her blue tablets on the next day after ingestion of the last peach tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Any time a subsequent cycle of Trivora 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 Trivora 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 (blue, white, or pink) 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 peach tablets, she is still protected against pregnancy provided she begins taking blue tablets again on the proper day. Trivora may be initiated no earlier than day 28 postpartum in the non-lactating mother or after a second trimester abortion due to the increased risk for thromboembolism (see " CONTRAINDICATIONS ", " WARNINGS " and " PRECAUTIONS " concerning thromboembolic disease). The patient should be advised to use a nonhormonal back-up method for the first 7 days of tablet-taking. However, if intercourse has already occurred, pregnancy should be excluded before the start of combined oral contraceptive use or the patient must wait for her first menstrual period. In the case of first-trimester abortion, if the patient starts Trivora immediately, additional contraceptive measures are not needed. It is to be noted that early resumption of ovulation may occur if Parlodel® (bromocriptine mesylate) has been used for the prevention of lactation.
Pregnancy and lactation
13. Nursing Mothers Small amounts of oral-contraceptive steroids and/or metabolites 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, combination 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.

Interactions

9. Drug Interactions Interactions between ethinyl estradiol and other substances may lead to decreased or increased serum ethinyl estradiol concentrations. Decreased ethinyl estradiol plasma concentrations may cause an increased incidence of breakthrough bleeding and menstrual irregularities and may possibly reduce efficacy of the combination oral contraceptive. Reduced ethinyl estradiol concentrations have been associated with concomitant use of substances that induce hepatic microsomal enzymes, such as rifampin, rifabutin, barbiturates, phenylbutazone, phenytoin sodium, griseofulvin, topiramate, some protease inhibitors, modafinil, and possibly St. John's wort. Substances that may decrease plasma ethinyl estradiol concentrations by other mechanisms include any substance that reduces gut transit time and certain antibiotics (e.g. ampicillin and other penicillins, tetracyclines) by a decrease of enterohepatic circulation of estrogens. During concomitant use of ethinyl estradiol containing products and substances that may lead to decreased plasma steroid hormone concentrations, it is recommended that a nonhormonal back-up method of birth control be used in addition to the regular intake of Trivora (levonorgestrel and ethinyl estradiol tablets-triphasic regimen). If the use of a substance which leads to decreased ethinyl estradiol plasma concentrations is required for a prolonged period of time, combination oral contraceptives should not be considered the primary contraceptive. After discontinuation of substances that may lead to decreased ethinyl estradiol plasma concentrations, use of a nonhormonal back-up method of birth control is recommended for 7 days. Longer use of a back-up method is advisable after discontinuation of substances that have led to induction of hepatic microsomal enzymes, resulting in decreased ethinyl estradiol concentrations. It may take several weeks until enzyme induction has completely subsided, depending on dosage, duration of use, and rate of elimination of the inducing substance. Some substances may increase plasma ethinyl estradiol concentrations. These include: Competitive inhibitors for sulfation of ethinyl estradiol in the gastrointestinal wall, such as ascorbic acid (vitamin C) and acetaminophen. Substances that inhibit cytochrome P450 3A4 isoenzymes such as indinavir, fluconazole, and troleandomycin. Troleandomycin may increase the risk of intrahepatic cholestasis during coadministration with combination oral contraceptives. Atorvastatin (unknown mechanism). Ethinyl estradiol may interfere with the mechanism of other drugs by inhibiting hepatic microsomal enzymes or by inducing hepatic drug conjugation, particularly glucuronidation. Accordingly, tissue concentrations may be either increased (e.g. cyclosporine, theophylline, corticosteroids) or decreased. The prescribing information of concomitant medications should be consulted to identify potential interactions. Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer Trivora with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see Warnings RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT).

More information

Category Value
Authorisation number ANDA074538
Orphan designation No
Product NDC 51862-510
Date Last Revised 03-08-2017
Type HUMAN PRESCRIPTION DRUG
RXCUI 748797
Storage and handling Store at 20° - 25°C (68° - 77°F). [See USP controlled room temperature.]
Marketing authorisation holder Mayne Pharma Inc.
Warnings Cigarette smoking increases the risk of serious cardiovascular side effects from oral-contraceptive use. This risk increases with age and with the extent of smoking (in epidemiologic studies, 15 or more cigarettes per day was associated with a significantly increased risk) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke.