Levonest Drug Information

Dosage and Administration To achieve maximum contraceptive effectiveness, LEVONEST™ Tablets (levonorgestrel and ethinyl estradiol tablets-triphasic regimen) must be taken exactly as directed and at intervals not exceeding 24 hours. LEVONEST™ Tablets (levonorgestrel and ethinyl estradiol tablets-triphasic regimen) are a three-phase preparation plus 7 inert tablets. The dosage of LEVONEST™ Tablets is one tablet daily for 28 consecutive days per menstrual cycle in the following order: 6 yellow tablets (phase 1), followed by 5 green tablets (phase 2), followed by 10 light brown tablets (phase 3), plus 7 white inert tablets, according to the prescribed schedule.

It is recommended that LEVONEST™ 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 LEVONEST™ Tablet daily in the order of 6 yellow, 5 green, 10 light brown tablets, and then 7 white inert tablets for twenty-eight consecutive days, beginning on day one of her menstrual cycle. (The first day of menstruation is day one.) Withdrawal bleeding usually occurs within 3 days following the last light brown tablet. (If LEVONEST™ 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 LEVONEST™ 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, LEVONEST™ 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 LEVONEST™ Tablets on the same day of the week that she began her first course, following the same schedule. She begins taking her yellow tablets on the next day after ingestion of the last white tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Any time a subsequent cycle of LEVONEST™ 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 LEVONEST™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 (yellow, green, or light brown) 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 white tablets, she is still protected against pregnancy provided she begins taking yellow tablets again on the proper day.

In the nonlactating mother, LEVONEST™ may be initiated postpartum, for contraception. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postparturn 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 Parlodel ® (bromocriptine mesylate) has been used for the prevention of lactation.

Adverse Reactions To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. An increased risk of the following serious adverse reactions has been associated with the use of oral- contraceptives (see “ Warings ” section): Thrombophlebitis. Arterial thromboembolism.

Pulmonary embolism. Myocardial infarction. Cerebral hemorrhage.

Cerebral thrombosis. Hypertension. Gallbladder disease.

Hepatic adenomas or benign liver tumors. Postmarketing 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 to 1.12 (Figure 1). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1). 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 to 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 to 10 years of COC use. Figure 1: Relevant Studies of Risk of Breast Cancer with Combined Oral Contraceptives 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. 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, 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. Figure 1

Levonest™ 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. Cerebral-vascular or coronary-artery disease.

Current diagnosis or history of breast cancer, which may be hormone sensitive. Undiagnosed abnormal genital bleeding. Cholestatic jaundice of pregnancy or jaundice with prior pill use.

Hepatic adenomas and carcinomas. Known or suspected pregnancy. Women who are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for alanine aminotransferase (ALT) elevations (see WARNINGS, RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT ).

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. Noncontraceptive Health Benefits The following noncontraceptive 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.