ZOVIA 1/35E-21

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZOVIA 1/35E-21 (ZOVIA 1/35E-21).

How it works

Combination estrogen-progestin contraceptive; suppresses gonadotropin release, inhibits ovulation, alters cervical mucus and endometrial lining.

What the body does with it

Metabolism	Ethinyl estradiol and norethindrone are metabolized primarily via CYP3A4; undergoes sulfate and glucuronide conjugation.
Excretion	Renal (approximately 40% as parent drug and metabolites; 20-40% as metabolites; 15-20% as unchanged drug), fecal (30-50% via bile as metabolites), and less than 2% in breast milk.
Half-life	Norethindrone: 5-12 hours (terminal elimination half-life, approximately 8 hours). Ethinyl estradiol: biphasic with terminal half-life of 10-20 hours (mean 15 hours). Clinical context: Steady state reached in 5-7 days.
Protein binding	Norethindrone: 61% bound to albumin, 36% bound to SHBG (sex hormone-binding globulin); Ethinyl estradiol: 97% bound, primarily to albumin (98%) and SHBG (2%).
Volume of Distribution	Norethindrone: 3.6 ± 0.8 L/kg; Ethinyl estradiol: 2.7-5.9 L/kg (mean approximately 3.5 L/kg). Indicates extensive tissue distribution.
Bioavailability	Oral: norethindrone 50-80% (mean 65%) due to first-pass metabolism; ethinyl estradiol 38-48% (mean 45%) due to first-pass conjugation in gut wall and liver.
Onset of Action	7 days of consistent daily dosing for contraceptive effect (follicle suppression requires at least 7 days).
Duration of Action	1 month (21 days active pills followed by 7 placebo days; contraceptive protection maintained during placebo week if all active pills taken correctly).

Classification & Brands

Dosing & administration

One tablet orally once daily at the same time each day for 21 days, followed by 7 placebo tablets (if included in the pack) or a 7-day pill-free interval. Each tablet contains ethinyl estradiol 0.035 mg and norethindrone 1 mg.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment or acute renal failure due to potential for adverse effects from estrogen component.
Liver impairment	Contraindicated in hepatic impairment classified as Child-Pugh class B or C (moderate to severe). In mild hepatic impairment (Child-Pugh A), use with caution and monitor hepatic function; consider alternative contraception.
Pediatric use	Safety and efficacy established in post-menarchal females. Dosing is same as adults: one tablet orally once daily for 21 days followed by 7 days off. Not indicated for use before menarche.
Geriatric use	Not indicated for use in postmenopausal women. No specific dosing recommendations; use alternative therapies for contraception or hormone replacement in geriatric population.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ZOVIA 1/35E-21 (ZOVIA 1/35E-21).

Breastfeeding	Small amounts of ethinyl estradiol and norethindrone are excreted in breast milk. M/P ratio not well defined. May reduce milk production and composition. Use is generally not recommended during breastfeeding, especially in the early postpartum period.
Teratogenic Risk	FDA Pregnancy Category X. Contraindicated in pregnancy. First trimester: risk of cardiovascular defects, limb reduction defects, and neural tube defects. Second/third trimesters: associated with fetal adrenal suppression, masculinization of female fetuses, and other virilization effects. Use in pregnancy may cause irreversible harm.

Warnings & precautions

■ FDA Black Box Warning

Cigarette smoking increases risk of serious cardiovascular events from combination hormonal contraceptives. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women >35 years who smoke should not use.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Thrombophlebitis or thromboembolic disorders","Cerebrovascular or coronary artery disease","Known or suspected breast carcinoma","Undiagnosed abnormal genital bleeding","Known/suspected pregnancy","Liver tumor (benign/malignant) or active liver disease","Age >35 and smoking ≥15 cigarettes/day","Tobacco use in women >35 years"]

Clinical Precautions

Precautions

["Increased risk of venous thromboembolism","Myocardial infarction","Stroke","Hepatic neoplasia","Gallbladder disease","Hypertension","Carbohydrate/lipid effects","Ocular lesions (retinal thrombosis)","Possible increased risk of breast cancer"]

Clinical Tips & Counseling

Drug interactions

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ZOVIA 1/35E-21

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZOVIA 1/35E-21 (ZOVIA 1/35E-21).

How it works

Combination estrogen-progestin contraceptive; suppresses gonadotropin release, inhibits ovulation, alters cervical mucus and endometrial lining.

What the body does with it

Metabolism	Ethinyl estradiol and norethindrone are metabolized primarily via CYP3A4; undergoes sulfate and glucuronide conjugation.
Excretion	Renal (approximately 40% as parent drug and metabolites; 20-40% as metabolites; 15-20% as unchanged drug), fecal (30-50% via bile as metabolites), and less than 2% in breast milk.
Half-life	Norethindrone: 5-12 hours (terminal elimination half-life, approximately 8 hours). Ethinyl estradiol: biphasic with terminal half-life of 10-20 hours (mean 15 hours). Clinical context: Steady state reached in 5-7 days.
Protein binding	Norethindrone: 61% bound to albumin, 36% bound to SHBG (sex hormone-binding globulin); Ethinyl estradiol: 97% bound, primarily to albumin (98%) and SHBG (2%).
Volume of Distribution	Norethindrone: 3.6 ± 0.8 L/kg; Ethinyl estradiol: 2.7-5.9 L/kg (mean approximately 3.5 L/kg). Indicates extensive tissue distribution.
Bioavailability	Oral: norethindrone 50-80% (mean 65%) due to first-pass metabolism; ethinyl estradiol 38-48% (mean 45%) due to first-pass conjugation in gut wall and liver.
Onset of Action	7 days of consistent daily dosing for contraceptive effect (follicle suppression requires at least 7 days).
Duration of Action	1 month (21 days active pills followed by 7 placebo days; contraceptive protection maintained during placebo week if all active pills taken correctly).

Classification & Brands

Dosing & administration

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment or acute renal failure due to potential for adverse effects from estrogen component.
Liver impairment	Contraindicated in hepatic impairment classified as Child-Pugh class B or C (moderate to severe). In mild hepatic impairment (Child-Pugh A), use with caution and monitor hepatic function; consider alternative contraception.
Pediatric use	Safety and efficacy established in post-menarchal females. Dosing is same as adults: one tablet orally once daily for 21 days followed by 7 days off. Not indicated for use before menarche.
Geriatric use	Not indicated for use in postmenopausal women. No specific dosing recommendations; use alternative therapies for contraception or hormone replacement in geriatric population.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ZOVIA 1/35E-21 (ZOVIA 1/35E-21).

Breastfeeding	Small amounts of ethinyl estradiol and norethindrone are excreted in breast milk. M/P ratio not well defined. May reduce milk production and composition. Use is generally not recommended during breastfeeding, especially in the early postpartum period.
Teratogenic Risk	FDA Pregnancy Category X. Contraindicated in pregnancy. First trimester: risk of cardiovascular defects, limb reduction defects, and neural tube defects. Second/third trimesters: associated with fetal adrenal suppression, masculinization of female fetuses, and other virilization effects. Use in pregnancy may cause irreversible harm.