Wymzya Fe - Drug Monograph

Introduction

Wymzya Fe is a combination oral contraceptive product containing norethindrone acetate and ethinyl estradiol, with ferrous fumarate as an iron supplement. It is a phasic regimen oral contraceptive packaged in a 28-day blister pack, with 24 active hormonal tablets followed by 4 iron-containing placebo tablets. This monograph provides comprehensive information about Wymzya Fe for healthcare professionals and educated patients.

Mechanism of Action

Wymzya Fe exerts its contraceptive effects through multiple mechanisms. The estrogen component (ethinyl estradiol) suppresses follicle-stimulating hormone (FSH) secretion, inhibiting follicular development. The progestin component (norethindrone acetate) suppresses luteinizing hormone (LH) secretion, preventing ovulation. Additionally, progestin thickens cervical mucus, creating a barrier to sperm penetration, and causes endometrial changes that reduce the likelihood of implantation.

Indications

• Prevention of pregnancy
• Treatment of moderate acne vulgaris in females at least 15 years of age who have no known contraindications to oral contraceptive therapy, have achieved menarche, and desire contraception

Dosage and Administration

• Standard dosing: One tablet daily for 28 consecutive days
• Initial regimen: Begin on Day 1 of menstrual period or first Sunday after period begins
• Switching from other contraceptives: Follow specific transition guidelines
• Postpartum: May start 4 weeks postpartum in non-breastfeeding women
• Missed dose: Follow specific instructions based on number of tablets missed and week of cycle

• Renal impairment: No dosage adjustment required
• Hepatic impairment: Contraindicated in hepatic disease
• Geriatric: Not indicated in postmenopausal women
• Pediatric: Safety and efficacy established for women who have reached menarche

Pharmacokinetics

• Absorption: Norethindrone acetate rapidly hydrolyzed to norethindrone; peak concentrations reached within 2 hours
• Distribution: Ethinyl estradiol highly bound to serum albumin; norethindrone bound to SHBG
• Metabolism: Hepatic metabolism via cytochrome P450 system (CYP3A4)
• Elimination: Ethinyl estradiol terminal half-life ~24 hours; norethindrone terminal half-life ~8 hours
• Excretion: Primarily renal and fecal elimination

Contraindications

• Current or history of thrombophlebitis or thromboembolic disorders
• Known or suspected carcinoma of the breast
• Known or suspected estrogen-dependent neoplasia
• Undiagnosed abnormal genital bleeding
• Current or history of cerebrovascular or coronary artery disease
• Liver tumors or active liver disease
• Known or suspected pregnancy
• Hypersensitivity to any component of Wymzya Fe

Warnings and Precautions

• Cardiovascular risks: Increased risk of thrombotic and thromboembolic events including stroke, MI, and venous thromboembolism
• Carcinoma: Breast cancer risk may be increased; monitor breast changes
• Hepatic effects: Risk of hepatic adenomas, hepatocellular carcinoma, and gallbladder disease
• Hypertension: Blood pressure monitoring recommended
• Carbohydrate metabolism: Carefully monitor prediabetic and diabetic women
• Depression: May exacerbate depression; monitor mood changes
• Bleeding irregularities: Evaluate unscheduled bleeding if persistent
• Vision changes: Discontinue if unexplained vision loss, papilledema, or retinal vascular lesions occur

Drug Interactions

• Enzyme inducers: Carbamazepine, phenytoin, rifampin, St. John's wort may decrease efficacy
• Antibiotics: Broad-spectrum antibiotics may reduce enterohepatic recirculation
• HIV medications: Protease inhibitors and NNRTIs may affect contraceptive levels
• Anticoagulants: May affect anticoagulant activity
• Cyclosporine: Increased cyclosporine levels possible
• Lamotrigine: May decrease lamotrigine levels
• Thyroid hormones: May affect thyroid hormone replacement requirements

Adverse Effects

• Headache
• Nausea
• Breast tenderness
• Irregular bleeding
• Weight changes

• Venous thromboembolism
• Arterial thromboembolism
• Hypertension
• Hepatic adenomas
• Gallbladder disease
• Mood changes and depression

• Acne improvement or exacerbation
• Libido changes
• Visual changes
• Glucose intolerance

Monitoring Parameters

• Blood pressure at baseline and periodically
• BMI and weight changes
• Signs and symptoms of thromboembolism
• Liver function tests if clinically indicated
• Lipid profile in women with hyperlipidemia
• Cervical cytology per screening guidelines
• Breast examination and mammography per screening guidelines
• Visual changes or ocular symptoms
• Mood changes and depressive symptoms

Patient Education

• Take tablet at same time each day
• Use backup contraception during first 7 days of initial use
• Missed dose instructions vary by number of tablets missed
• Report severe abdominal pain, chest pain, headaches, eye problems, or leg pain immediately
• Notify healthcare providers of oral contraceptive use
• Does not protect against HIV or other sexually transmitted infections
• Iron tablets may cause gastrointestinal upset; take with food if needed
• Report persistent irregular bleeding
• Smoking increases serious cardiovascular risks, especially after age 35

References

1. Wymzya Fe [package insert]. Rockville, MD: Mayne Pharma; 2021. 2. Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(3):1-103. 3. Tepper NK, Marchbanks PA, Curtis KM. Update to CDC's U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: Revised Recommendations for the Use of Hormonal Contraception Among Women at High Risk for HIV Infection. MMWR Morb Mortal Wkly Rep. 2020;69(14):405-410. 4. Arowojolu AO, Gallo MF, Lopez LM, Grimes DA. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. 2012;(7):CD004425. 5. Stegeman BH, de Bastos M, Rosendaal FR, et al. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ. 2013;347:f5298. 6. Practice Bulletin No. 206: Use of Hormonal Contraception in Women with Coexisting Medical Conditions. Obstet Gynecol. 2019;133(2):e128-e150.