Professional Information — Marlissa 28 Day

Indications and Usage

MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) is indicated for use by females of reproductive potential to prevent pregnancy.

Dosage and Administration

1. How to Start and Take MARLISSA^® (levonorgestrel and ethinyl estradiol tablets)

MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) is dispensed in a compact dispenser containing 28 tablets (see HOW SUPPLIED). MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) may be started using either a Day 1 start or a Sunday start (see Table 3). For the first cycle of a Sunday start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration.

Table 3: Instructions for Administration of MARLISSA^® (levonorgestrel and ethinyl estradiol tablets)

Starting MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) after Abortion or Miscarriage

First-trimester

• After a first-trimester abortion or miscarriage, MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) may be started immediately. An additional method of contraception is not needed if MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) is started immediately.
• If MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms or spermicide) for the first seven days of her first cycle of MARLISSA^® (levonorgestrel and ethinyl estradiol tablets).

Second-trimester

• Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) following the instructions in Table 3 for Day 1 or Sunday start. Use additional non-hormonal contraception (such as condoms or spermicide) for the first seven days of the patient’s first cycle of MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) (see CONTRAINDICATIONS, WARNINGS (1), PRECAUTIONS (10) and FDA-APPROVED PATIENT LABELING).

Starting MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) after Childbirth

• Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) following the instructions in Table 3 for women not currently using hormonal contraception.
• MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) is not recommended for use in lactating women (see PRECAUTIONS (7) and FDA-APPROVED PATIENT LABELING).
• If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) (see CONTRAINDICATIONS, WARNINGS (9), PRECAUTIONS (6) and FDA‑ APPROVED PATIENT LABELING).

2. Dosing MARLISSA^® (levonorgestrel and ethinyl estradiol tablets)

Instruct patients to take one tablet by mouth at the same time every day. To achieve maximum contraceptive effectiveness, patients must take MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) as directed, in the order directed on the blister pack. The failure rate may increase when pills are missed or taken incorrectly.

3. Missed doses

Instruct patients about the handling of missed doses (e.g., to take single missed pills as soon as possible) and to follow the dosing instructions provided in the FDA-approved patient labeling.

Table 4: Instructions for Missed MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) Tablets

4. Advice in Case of Gastrointestinal Disturbances

If vomiting occurs within 3 to 4 hours after taking MARLISSA^® (levonorgestrel and ethinyl estradiol tablets), the patient should proceed as if she missed a tablet. In case of prolonged vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken.

Contraindications

MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) is contraindicated in females who are known to have the following conditions:

• A high risk of arterial or venous thrombotic diseases. Examples include women who are known to:
  • oSmoke, if over age 35 [see BOXED WARNING and WARNINGS (1)].
  • oHave current or history of deep vein thrombosis or pulmonary embolism [see WARNINGS (1)].
  • oHave cerebrovascular disease [see WARNINGS (1)].
  • oHave coronary artery disease [see WARNINGS (1)].
  • oHave thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see WARNINGS (1)].
  • oHave inherited or acquired hypercoagulopathies [see WARNINGS (1)].
  • oHave uncontrolled hypertension or hypertension with vascular disease [see WARNINGS (3)].
  • oHave diabetes mellitus and are over age 35, diabetes mellitus with hypertension or vascular disease or other end-organ damage, or diabetes mellitus of >20 years duration [see WARNINGS (7)].
  • oHave headaches with focal neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see WARNINGS (8)].
• Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive.
• Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see WARNINGS (2)].
• Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see WARNINGS (5)].
• Undiagnosed abnormal uterine bleeding [see WARNINGS (9)].

Adverse Reactions

The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling:

• Serious cardiovascular adverse events [see BOXED WARNING and WARNINGS (1)]
• Vascular events [see WARNINGS (1)]
• Liver disease [see WARNINGS (2)]
• Hypertension [see WARNINGS (3)]
• Gallbladder disease [see WARNINGS (6)]
• Carbohydrate and lipid effects [see WARNINGS (7)]
• Headache [see WARNINGS (8)]
• Carcinoma of the cervix [see WARNINGS (11)]

Adverse reactions reported by COC users and described elsewhere in the labeling are:

• Bleeding irregularities and amenorrhea [see WARNINGS (9)]
• Mood changes, including depression [see WARNINGS (10)]
• Melasma/chloasma which may persist [see WARNINGS (14)]
• Edema/fluid retention [see PRECAUTIONS (2)]
• Diminution in lactation when given immediately postpartum [see PRECAUTIONS (7)]

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 to 1.12 (Figure 2).

Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 2). 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 2: 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.

The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related: Breast tenderness, pain, enlargement, secretion; Nausea, vomiting and gastrointestinal symptoms (such as abdominal pain, cramps and bloating); Change in menstrual flow; Temporary infertility after discontinuation of treatment; Change in weight or appetite (increase or decrease); Change in cervical erosion and secretion; Cholestatic jaundice; Rash (allergic); 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.

Overdosage

There have been no reports of serious adverse outcomes from overdose of COCs, including ingestion by children. Overdose may cause uterine bleeding in females and nausea.

Description

MARLISSA^® (levonorgestrel and ethinyl estradiol tablets) is a combination oral contraceptive (COC) consisting of 21 light orange to orange color MARLISSA ^® (levonorgestrel and ethinyl estradiol tablets), each containing 0.15 mg of levonorgestrel, USP, a totally synthetic progestogen, and 0.03 mg of ethinyl estradiol, USP, an estrogen and 7 light pink to pink inert tablets (without hormones).

The structural formulas for the active components are:

                                                             Levonorgestrel, USP

                                                           C₂₁H₂₈O₂ MW: 312.4

Levonorgestrel, USP is chemically d(-)-13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one

                                                           Ethinyl Estradiol, USP

                                                       C₂₀H₂₄O₂ MW: 296.4

Ethinyl Estradiol, USP is 19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3, 17-diol.

Each light orange to orange color active tablet contains the following inactive ingredients: FD&C Yellow no. 6, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polacrilin potassium, povidone and talc. In addition, the film-coating contains hypromellose and macrogol.

Each light pink to pink inert tablet contains the following inactive ingredients: D&C Red no. 30, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polacrilin potassium, povidone and talc.

Clinical Pharmacology

Combination oral contraceptives prevent pregnancy primarily by suppressing ovulation.

How Supplied / Storage and Handling

MARLISSA^® (levonorgestrel and ethinyl estradiol tablets, USP 0.15 mg/0.03 mg) is available in cartons (NDC 68462-388- 29) of 3 blisters (NDC 68462-388-84), each containing 28 tablets.

Each blister contains:

21 Active Tablets: Light orange to orange color, round, biconvex, film coated tablets with ‘A5’ debossed on one side.

7 Inert Tablets: Light pink to pink color, round, biconvex, uncoated tablets with ‘A6’ debossed on one side.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light.

Distributed by:

Glenmark Pharmaceuticals Inc., USA

Elmwood Park, NJ 07407

Questions? 1 (888) 721-7115

www.glenmarkpharma-us.com

April 2025