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. |
| Molecular Weight | Norethindrone: 298.42 Da; Ethinyl estradiol: 296.40 Da |
| Action Class | Oral Contraceptive; Estrogen-Progestin Combination |
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 | Avoid. Combination hormonal contraceptives are contraindicated during pregnancy due to risk of fetal harm. |
| 2nd trimester | Avoid. No therapeutic indication during pregnancy; contraindicated. |
| 3rd trimester | Avoid. No therapeutic indication during pregnancy; contraindicated. |
Clinical note
Comprehensive clinical and safety monograph for ZOVIA 1/35E-28 (ZOVIA 1/35E-28).
| Placental transfer | Yes, ethinyl estradiol and norethindrone cross the placenta. |
| Breastfeeding | Combination hormonal contraceptives may reduce milk production and pass into breast milk. Use alternative contraception if breastfeeding. |
| Lactation Rating |
■ 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.
| Common Effects | Nausea, Headache, Breast tenderness, Weight changes, Irregular menstrual bleeding (spotting, breakthrough bleeding), Mood changes (depression, anxiety), Acne, Fluid retention |
| Serious Effects | Venous thromboembolism (deep vein thrombosis, pulmonary embolism), Arterial thromboembolism (myocardial infarction, stroke), Hepatic adenoma or hepatocellular carcinoma, Hypertension, Gallbladder disease (cholelithiasis, cholecystitis), Cerebral hemorrhage, Retinal thrombosis |
History of venous thromboembolismActive liver disease or hepatic impairmentKnown or suspected pregnancyBreast cancer or other estrogen-sensitive neoplasiaUncontrolled hypertension (≥160/100 mmHg)Major surgery with prolonged immobilizationMigraine with aura (age ≥35)Diabetes with vascular involvementSmoking (age ≥35 and ≥15 cigarettes/day)
| Precautions |
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| L4 (Possibly Hazardous) |
| 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. |
| 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. |
| 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. |
| Food/Dietary | No significant food interactions. Grapefruit juice may slightly increase estrogen levels but is not contraindicated. Maintain consistent dietary habits to avoid fluctuations in efficacy. |
| Clinical Pearls | Zovia 1/35E-28 is a monophasic oral contraceptive containing ethinyl estradiol 35 mcg and ethynodiol diacetate 1 mg. It has a higher progestin dose compared to low-dose pills, which may increase androgenic side effects like acne or hirsutism. Breakthrough bleeding is common in the first 3 cycles. It is not recommended for patients with a history of thromboembolic disorders, migraine with aura, or liver disease. Monitor blood pressure at each visit; estrogen component may raise BP. Efficacy is reduced with concurrent use of CYP3A4 inducers such as rifampin or certain anticonvulsants. |
| Patient Advice | Take one tablet daily at the same time each day, with or without food. · If you miss a pill, refer to the package insert instructions; use backup contraception as directed. · Common side effects include nausea, breast tenderness, and spotting, which often improve after the first few cycles. · Do not smoke while taking this medication; smoking increases the risk of serious cardiovascular events. · Inform your healthcare provider if you experience severe headaches, chest pain, leg pain or swelling, or vision changes. · This medication does not protect against sexually transmitted infections or HIV. |