ZOVIA 1/35E-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOVIA 1/35E-28 (ZOVIA 1/35E-28).
ZOVIA 1/35E-28 is a combined oral contraceptive (COC) containing ethinyl estradiol and norethindrone. It inhibits ovulation via suppression of gonadotropins (FSH and LH), increases cervical mucus viscosity, and alters endometrial receptivity.
| Metabolism | Ethinyl estradiol: primarily metabolized by CYP3A4, with sulfation and glucuronidation. Norethindrone: metabolized via reduction and conjugation (glucuronidation and sulfation); minor CYP-mediated pathways. |
| Excretion | Renal: ~40% as metabolites; biliary/fecal: ~40% as metabolites; unchanged drug minimal (<1%). |
| Half-life | Ethinyl estradiol: ~17 hours (range 13-27 hours); Norethindrone: ~8 hours (range 5-14 hours). Clinical context: Steady state achieved in ~5-7 days; contraceptive effect requires consistent dosing. |
| Protein binding | Ethinyl estradiol: 98% bound to albumin; Norethindrone: 80% bound to albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Ethinyl estradiol: ~3-5 L/kg; Norethindrone: ~4 L/kg; both widely distributed with tissue penetration. |
| Bioavailability | Oral: Ethinyl estradiol ~40-50% (first-pass metabolism); Norethindrone ~65% (first-pass metabolism). |
| Onset of Action | Oral: Contraceptive effect achieved within 7 days when started on day 1 of menses; immediate if started on day 1 of cycle. |
| Duration of Action | Oral: 24 hours; suppression of ovulation maintained with daily dosing; missed pills increase failure risk. |
One tablet orally once daily at the same time each day for 21 days, followed by 7 days of placebo (inactive tablets), then repeat.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment or acute renal failure due to potential fluid retention and hyperkalemia. |
| Liver impairment | Contraindicated in acute hepatic disease, hepatocellular carcinoma, or history of cholestatic jaundice with prior oral contraceptive use. Not recommended for Child-Pugh class B or C due to impaired steroid metabolism. |
| Pediatric use | Approved for use in females after menarche. Same dosing as adults: one tablet daily for 21 days, then 7 placebo days. Not indicated for use before menarche. |
| Geriatric use | Not indicated for use after menopause. No specific dosage adjustments; consider increased risk of thromboembolic events and cardiovascular disease in older women with additional risk factors. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZOVIA 1/35E-28 (ZOVIA 1/35E-28).
| Breastfeeding | Small amounts of ethinyl estradiol and norethindrone pass into breast milk; may reduce milk production and quality. M/P ratio not established. Use only if benefits outweigh risks; consider alternative contraception. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: Increased risk of congenital anomalies, including cardiovascular and limb defects. Second and third trimesters: Associated with fetal toxicity, including masculinization of female fetuses (progestin effect). Discontinue if pregnancy occurs. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from COC use. The risk increases with age and especially in women >35 years who smoke ≥15 cigarettes/day. COCs should not be used by such women.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders, cerebrovascular or coronary artery disease, known or suspected breast cancer, estrogen-dependent neoplasia, undiagnosed abnormal genital bleeding, pregnancy, liver tumors or active liver disease, hypersensitivity to any component, and smoking ≥15 cigarettes/day in women >35 years.
| Precautions | Increased risk of thromboembolic disorders (e.g., VTE, stroke, MI), especially in smokers or older women. Hepatic neoplasia, gallbladder disease, hypertension, carbohydrate/lipid effects, ocular lesions, and mood changes. Discontinue if jaundice, visual disturbances, or severe headache occurs. |
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| Fetal Monitoring |
| Monitor for signs of thromboembolism, hypertension, and hepatic dysfunction. In case of accidental pregnancy, assess fetal development via ultrasound. No routine fetal monitoring required. |
| Fertility Effects | Suppresses ovulation; after discontinuation, return to fertility may be delayed but is generally rapid (within 1-3 months). No permanent adverse effects on fertility. |