Professional Information — Lessina

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 III 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, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.

^1. Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason.

^2. Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason.

^3. Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year.

^4. The percentages becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percentage who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether.

^5.Foams, creams, gels, vaginal suppositories, vaginal film.

^6. Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the postovulatory phases.

^7. With spermicidal cream or jelly.

^8. Without spermicides.

Dosage and Administration

To achieve maximum contraceptive effectiveness, Lessina^® (levonorgestrel and ethinyl estradiol tablets USP) must be taken exactly as directed at intervals not exceeding 24-hours.

Lessina Tablets are a monophasic preparation plus 7 inert tablets. The dosage of Lessina Tablets is one tablet daily for 21 consecutive days per menstrual cycle plus 7 white inert tablets according to the prescribed schedule. It is recommended that Lessina 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 pink Lessina Tablet daily 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 pink tablet. (If Lessina 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 Lessina 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, Lessina 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 Lessina Tablets on the same day of the week that she began her first course, following the same schedule. She begins taking her pink 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. Anytime a subsequent cycle of Lessina 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 Lessina 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 active 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 (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 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 pink tablets again on the proper day.

In the nonlactating mother, Lessina 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.

Contraindications

Lessina 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 of, or history of, breast cancer, which may be hormone-sensitive
• 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
• 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

Post Marketing 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 - 1.12 (Figure II).

Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure II). 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 - 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 8-10 years of COC use.

Figure II Risk of Breast Cancer with Combined Oral Contraceptive Use

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.

An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section).

• 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 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:

• Pre-menstrual 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

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.

Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation

Do not co-administer Lessina 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).

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.

Description

Each cycle of Lessina ^® 28 (levonorgestrel and ethinyl estradiol tablets USP) consists of 21 pink active tablets each containing 0.1 mg levonorgestrel, USP and 0.02 mg ethinyl estradiol, USP; and seven white inert tablets. The inactive ingredients include anhydrous lactose, FD&C red no. 40 aluminum lake, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, corn starch, and titanium dioxide. Each white tablet contains only inert ingredients as follows: anhydrous lactose, hypromellose, microcrystalline cellulose, and magnesium stearate.

The structural formulas are as follows:

Levonorgestrel, USP

C₂₁H₂₈O₂ Molecular Weight: 312.4

Ethinyl Estradiol, USP

C₂₀H₂₄O₂ Molecular Weight: 296.4

Clinical Pharmacology

Combination oral contraceptives 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).

How Supplied / Storage and Handling

Lessina^® (levonorgestrel and ethinyl estradiol tablets USP 0.1 mg/ 0.02 mg) are packaged in blister cards. Each card contains 21 pink, round, film-coated, biconvex, unscored tablets, debossed stylized b on one side and 965 on the other side, and 7 white, round, biconvex, unscored tablets, debossed stylized b on one side and 208 on the other side.

Available in cartons of 3 blister cards (NDC: 0555-9014-67).

Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature].

Patient Counseling Information

See “Patient Labeling” printed below.