Levonest

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 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) 1-9* 25 Withdrawal 4 19 No contraception (planned pregnancy) 85 85 NA – not available *Depending on method (calendar, ovulation, symptothermal, post-ovulation) Adapted from Hatcher RA et al, Contraceptive Technology : 17 t h Revised Edition . NY, NY: Ardent Media, Inc., 1998

DOSAGE AND ADMINISTRATION To achieve maximum contraceptive effectiveness, LEVONESTTM Tablets (levonorgestrel and ethinyl estradiol tablets—triphasic regimen) must be taken exactly as directed and at intervals not exceeding 24 hours. LEVONESTTM Tablets are a three-phase preparation plus 7 inert tablets. The dosage of LEVONESTTM 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 LEVONESTTM 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 LEVONESTTM Tablet daily in the order of 6 yellow, 5 green, 10 light brown tablets, and then 7 white 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 brown tablet and may not have finished before the next pack is started. (If LEVONESTTM 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 LEVONESTTM 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, LEVONESTTM 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 LEVONESTTM the next day. If switching from an implant or injection, the patient should start LEVONESTTM 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 LEVONESTTM 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 LEVONESTTM 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 LEVONESTTM 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 …

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 LEVONESTTM (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 ).

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

DESCRIPTION Each LEVONESTTM (levonorgestrel and ethinyl estradiol tablets—triphasic regimen) cycle of 28 tablets consists of three different drug phases as follows: Phase 1 comprised of 6 yellow tablets, each containing 0.050 mg of levonorgestrel ( d (-)-13 beta-ethyl-17-alpha-ethinyl-17-beta-hydroxygon-4-en-3-one), a totally synthetic progestogen, and 0.030 mg of ethinyl estradiol (19-nor-17 -pregna-1,3,5(10)-trien-20-yne-3, 17-diol); phase 2 comprised of 5 green tablets, each containing 0.075 mg levonorgestrel and 0.040 mg ethinyl estradiol; and phase 3 comprised of 10 light brown tablets, each containing 0.125 mg levonorgestrel and 0.030 mg ethinyl estradiol; then followed by 7 white inert tablets. The inactive ingredients present in the yellow, green and light brown tablets are lactose, magnesium stearate and pregelatinized corn starch. Each yellow tablet also contains FD&C Yellow #5 Aluminum Lake, FD&C Yellow #6 Aluminum Lake, FD&C Blue #2 Aluminum Lake, titanium dioxide, macrogol/ polyethylene glycol 3350 NF, lecithin (soya), talc, and polyvinyl alcohol. Each green tablet also contains FD&C Yellow #5 Aluminum Lake, FD&C Red #40 Aluminum Lake, FD&C Blue #2 Aluminum Lake, titanium dioxide, macrogol/ polyethylene glycol 3000 NF, lecithin (soya), talc, and polyvinyl alcohol. Each light brown tablet also contains iron oxide yellow, iron oxide red, iron oxide black, titanium dioxide, macrogol/ polyethylene glycol 3350 NF, lecithin (soya), talc, and polyvinyl alcohol. Each inactive, white tablet (7) contains the following inactive ingredients: Titanium dioxide, polydextrose, hypromellose, triacetin, macrogol/polyethylene glycol 8000, lactose, magnesium stearate and pregelatinized corn starch. image-01

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.

How Supplied LEVONESTTM Tablets (levonorgestrel and ethinyl estradiol tablets—triphasic regimen) are available in 28-tablet blister cards (NDC 16714-340-01). Each cycle contains 28 tablets as follows: • Six yellow tablets containing 0.05 mg of levonorgestrel and 0.03 mg of ethinyl estradiol. The yellow tablets are unscored, round in shape with "T1" debossed on one side. • Five green tablets containing 0.075 mg of levonorgestrel and 0.04 mg of ethinyl estradiol. The green tablets are unscored, round in shape with "T2" debossed on one side. • Ten light brown tablets containing 0.125 mg of levonorgestrel and 0.03 mg of ethinyl estradiol. The light brown tablets are unscored, round in shape with "T3" debossed on one side. • Seven white inert tablets. The white inert tablets are unscored, round in shape with "P" debossed on one side and " N " on the other side. LEVONESTTM Tablets are available in the following: Carton of 1 NDC 16714-340-02 Carton of 3 NDC 16714-340-03 Carton of 6 NDC 16714-340-04 Store at 20°-25°C (68°-77°F). [See USP controlled room temperature.] References available upon request. Manufactured for: Northstar Rx LLC Memphis, TN 38141 Manufactured by: Novast Laboratories Ltd. Nantong, China 226009 I 0105 Rev. 06/2023 Rev.B Brief Summary Patient Package Insert This product (like all oral contraceptives) is intended to prevent pregnancy. It does 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, jaundice, or malignant or benign liver tumors. You should not take the pill if you take any Hepatitis C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may increase levels of the liver enzyme “alanine aminotransferase” (ALT) in the blood. 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 eff ects on the heart and blood vessels 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 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 vessel 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 …