Introduction
Vyfemla is a combination oral contraceptive pill (OCP) containing ethinyl estradiol and norethindrone acetate. It belongs to the class of monophasic hormonal contraceptives and is FDA-approved for pregnancy prevention. This monograph provides comprehensive clinical information for healthcare professionals managing patients on this contraceptive regimen.
Mechanism of Action
Vyfemla works through multiple mechanisms to prevent pregnancy:
- Suppression of ovulation via negative feedback on hypothalamic-pituitary axis
- Alteration of cervical mucus (increased viscosity prevents sperm penetration)
- Endometrial changes that create an unfavorable environment for implantation
- Modification of tubal motility affecting ovum transport
The combination of estrogen and progestin components synergistically provides reliable contraception with a Pearl Index of approximately 0.3-2.0 pregnancies per 100 woman-years.
Indications
- Pregnancy prevention
- Management of moderate acne in females at least 15 years old who have no known contraindications to oral contraceptive therapy, desire contraception, have achieved menarche, and are unresponsive to topical anti-acne medications
Dosage and Administration
Standard regimen: One white active tablet daily for 21 consecutive days followed by one green inert tablet daily for 7 days- Initiation: Start on first day of menstrual period or first Sunday after period begins
- Missed dose protocol:
- 1 tablet missed: Take as soon as remembered - 2 consecutive tablets missed: Take 2 tablets daily for 2 days, then resume regular schedule - 3+ consecutive tablets missed: Discard pack, begin new pack on Sunday; use backup contraception for 7 days
Special populations:- Postpartum: May initiate 4 weeks postpartum in non-breastfeeding women
- Post-abortion: May initiate immediately or within 7 days
- Hepatic impairment: Contraindicated in acute or severe liver disease
- Renal impairment: No dosage adjustment required
Pharmacokinetics
Absorption: Ethinyl estradiol: ~60% bioavailability; Norethindrone acetate: completely converted to norethindrone with absolute bioavailability ~65% Distribution: Ethinyl estradiol: Vd ~5 L/kg; Norethindrone: Vd ~4 L/kg; Both highly protein-bound (ethinyl estradiol: 98% to albumin; norethindrone: 96% to albumin and SHBG) Metabolism: Hepatic metabolism via CYP3A4; extensive first-pass metabolism; ethinyl estradiol undergoes enterolepatic recirculation Elimination: Ethinyl estradiol: t½ ~24 hours; Norethindrone: t½ ~8 hours; Excretion primarily renal (60%) and fecal (40%)Contraindications
- Current or history of thrombophlebitis or thromboembolic disorders
- Cerebrovascular or coronary artery disease
- Known or suspected estrogen-dependent neoplasia
- Undiagnosed abnormal genital bleeding
- Known or suspected pregnancy
- Hepatic dysfunction or tumor
- Hypersensitivity to any component
- Smokers over 35 years old (>15 cigarettes/day)
Warnings and Precautions
Boxed Warning: Cigarette smoking increases risk of serious cardiovascular side effects; women over 35 who smoke should not use COCs Additional precautions:- Cardiovascular risks: Increased risk of MI, stroke, venous thromboembolism, and arterial thromboembolism
- Hypertension: Monitor blood pressure; may exacerbate hypertension
- Lipid metabolism: May adversely affect lipid profiles
- Carbohydrate metabolism: May decrease glucose tolerance
- Liver function: Discontinue if jaundice develops
- Depression: May precipitate or exacerbate depression
- Vision changes: May cause corneal edema or vascular lesions
- Surgery: Discontinue at least 4 weeks before elective surgery
Drug Interactions
Strong CYP3A4 inducers: Rifampin, carbamazepine, phenytoin, St. John's wort - may decrease efficacy Antibiotics: Broad-spectrum antibiotics may reduce enterohepatic recirculation HIV medications: Protease inhibitors and NNRTIs may alter contraceptive levels Anticoagulants: May decrease anticoagulant effect Antidiabetic agents: May alter glucose control requiring dosage adjustment Herbal supplements: St. John's wort may reduce efficacyAdverse Effects
Common (≥10%): Nausea, headache, breast tenderness, bloating, weight changes, mood changes, breakthrough bleeding Less common (1-10%): Acne changes, libido changes, melasma, chloasma, vaginal candidiasis Serious (<1%): Venous thromboembolism, arterial thrombosis, stroke, myocardial infarction, hepatic adenomas, gallbladder disease, hypertension Rare: Optic neuritis, retinal thrombosis, mesenteric thrombosisMonitoring Parameters
- Baseline: Blood pressure, BMI, lipid profile, liver function tests, fasting glucose
- Ongoing: Blood pressure at 3 months then annually; annual comprehensive history and physical
- Symptom monitoring: Headaches, visual changes, chest pain, shortness of breath, leg pain/swelling
- Laboratory: Liver enzymes if symptoms suggest hepatic dysfunction
- Cancer screening: Regular breast exams and Pap smears per guidelines
Patient Education
- Take tablet same time daily to maintain effectiveness
- Use backup contraception during first 7 days of initial cycle
- Report severe abdominal pain, chest pain, headaches, eye problems, or leg pain immediately
- Smoking increases serious risks - strongly advised to quit
- Does not protect against HIV or other sexually transmitted diseases
- May experience breakthrough bleeding during first few months
- Contact healthcare provider if vomiting or diarrhea occurs within 3-4 hours of taking active pill
- Schedule regular follow-up appointments for monitoring
References
1. FDA Prescribing Information: Vyfemla (norethindrone acetate and ethinyl estradiol) tablets 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. Teal S, Edelman A. Contraception Selection, Effectiveness, and Adverse Effects: A Review. JAMA. 2021;326(24):2507-2518. 4. Practice Bulletin No. 206: Use of Hormonal Contraception in Women with Coexisting Medical Conditions. Obstet Gynecol. 2019;133(3):e128-e150. 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. World Health Organization. Medical Eligibility Criteria for Contraceptive Use. 5th ed. Geneva: WHO; 2015.
This information is intended for educational purposes only and should not replace clinical judgment. Always consult current prescribing information and clinical guidelines.