ORTHO-NOVUM 1/80 21

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ORTHO-NOVUM 1/80 21 (ORTHO-NOVUM 1/80 21).

How it works

Combination estrogen-progestin contraceptive. Suppresses gonadotropin (FSH, LH) release from pituitary, inhibiting ovulation. Increases viscosity of cervical mucus, impeding sperm penetration. Induces endometrial thinning, reducing implantation likelihood.

What the body does with it

Metabolism	Ethinyl estradiol is primarily metabolized via CYP3A4; undergoes first-pass metabolism in gut and liver. Norethindrone is metabolized via reduction and conjugation (glucuronidation).
Excretion	Renal: ~60% (metabolites, primarily glucuronide and sulfate conjugates), Fecal: ~40% (biliary excretion of metabolites). Unchanged drug negligible.
Half-life	Norethindrone terminal half-life: 8-11 hours; Mestranol (ethinyl estradiol pro-drug) terminal half-life: 10-15 hours (metabolite ethinyl estradiol). Clinical context: Steady-state reached in 5-7 days; once-daily dosing maintains therapeutic levels.
Protein binding	Norethindrone: 60-70% bound to SHBG and albumin; Ethinyl estradiol: 95-98% bound to albumin.
Volume of Distribution	Norethindrone: Vd ~4 L/kg (0.9-4 L/kg); Ethinyl estradiol: Vd ~2.7 L/kg. Reflects extensive tissue distribution with accumulation in fat, liver, and reproductive organs.
Bioavailability	Oral: Norethindrone ~60-70% (first-pass metabolism); Mestranol undergoes hepatic demethylation to ethinyl estradiol, overall bioavailability of ethinyl estradiol ~40%.
Onset of Action	Oral: Onset of contraceptive effect occurs after 7 days of consistent dosing; for cycle control, effects on endometrium begin within days.
Duration of Action	Oral: Duration lasts 24 hours (once-daily dosing). For missed pills, contraceptive protection diminished beyond 36 hours if one pill missed, and >48 hours if multiple missed.

Classification & Brands

Dosing & administration

One tablet orally once daily for 21 consecutive days, followed by 7 days off therapy.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Insufficient data for severe impairment (GFR <30 mL/min); use with caution.
Liver impairment	Contraindicated in severe hepatic disease (Child-Pugh class C). Use with caution in mild to moderate impairment (Child-Pugh A/B); monitor liver function.
Pediatric use	Not indicated for use before menarche. For post-menarchal adolescents, same dosing as adults; no weight-based adjustment required.
Geriatric use	Not indicated for use after menopause. No specific dose adjustment for older women; consider increased risk of thromboembolic events and cardiovascular disease.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ORTHO-NOVUM 1/80 21 (ORTHO-NOVUM 1/80 21).

Breastfeeding	Excreted in breast milk; may reduce milk production and quality. M/P ratio not well established. Use during lactation not recommended.
Teratogenic Risk	First trimester: Increased risk of neural tube defects, cardiovascular anomalies, and oral clefts. Second and third trimesters: Associated with masculinization of female fetuses and potential for other congenital anomalies. Contraindicated in pregnancy.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Cigarette smoking increases risk of serious cardiovascular side effects from combination oral contraceptives. Risk increases with age (especially women over 35) and with heavy smoking (≥15 cigarettes/day). Women using ORTHO-NOVUM should be strongly advised not to smoke.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease (current or history)","Known or suspected breast carcinoma","Estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Pregnancy (confirmed or suspected)","Benign or malignant liver tumor (current or history)","Known or suspected pregnancy","Hypersensitivity to any component","Cigarette smoking in women over 35"]

Clinical Precautions

Precautions

["Increased risk of thromboembolic disorders (MI, stroke, DVT, PE)","Hepatic neoplasia (benign and malignant) reported","Increased risk of gallbladder disease","Elevated blood pressure","Carbohydrate intolerance (monitor diabetic patients)","Ocular lesions (retinal thrombosis, optic neuritis): discontinue if sudden vision loss, proptosis, or diplopia occurs","Depression: discontinue if severe or recurrent","Menstrual irregularities (breakthrough bleeding, amenorrhea)"]

Clinical Tips & Counseling

Drug interactions

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ORTHO-NOVUM 1/80 21

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ORTHO-NOVUM 1/80 21 (ORTHO-NOVUM 1/80 21).

How it works

What the body does with it

Metabolism	Ethinyl estradiol is primarily metabolized via CYP3A4; undergoes first-pass metabolism in gut and liver. Norethindrone is metabolized via reduction and conjugation (glucuronidation).
Excretion	Renal: ~60% (metabolites, primarily glucuronide and sulfate conjugates), Fecal: ~40% (biliary excretion of metabolites). Unchanged drug negligible.
Half-life	Norethindrone terminal half-life: 8-11 hours; Mestranol (ethinyl estradiol pro-drug) terminal half-life: 10-15 hours (metabolite ethinyl estradiol). Clinical context: Steady-state reached in 5-7 days; once-daily dosing maintains therapeutic levels.
Protein binding	Norethindrone: 60-70% bound to SHBG and albumin; Ethinyl estradiol: 95-98% bound to albumin.
Volume of Distribution	Norethindrone: Vd ~4 L/kg (0.9-4 L/kg); Ethinyl estradiol: Vd ~2.7 L/kg. Reflects extensive tissue distribution with accumulation in fat, liver, and reproductive organs.
Bioavailability	Oral: Norethindrone ~60-70% (first-pass metabolism); Mestranol undergoes hepatic demethylation to ethinyl estradiol, overall bioavailability of ethinyl estradiol ~40%.
Onset of Action	Oral: Onset of contraceptive effect occurs after 7 days of consistent dosing; for cycle control, effects on endometrium begin within days.
Duration of Action	Oral: Duration lasts 24 hours (once-daily dosing). For missed pills, contraceptive protection diminished beyond 36 hours if one pill missed, and >48 hours if multiple missed.

Classification & Brands

Dosing & administration

One tablet orally once daily for 21 consecutive days, followed by 7 days off therapy.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Insufficient data for severe impairment (GFR <30 mL/min); use with caution.
Liver impairment	Contraindicated in severe hepatic disease (Child-Pugh class C). Use with caution in mild to moderate impairment (Child-Pugh A/B); monitor liver function.
Pediatric use	Not indicated for use before menarche. For post-menarchal adolescents, same dosing as adults; no weight-based adjustment required.
Geriatric use	Not indicated for use after menopause. No specific dose adjustment for older women; consider increased risk of thromboembolic events and cardiovascular disease.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ORTHO-NOVUM 1/80 21 (ORTHO-NOVUM 1/80 21).

Breastfeeding	Excreted in breast milk; may reduce milk production and quality. M/P ratio not well established. Use during lactation not recommended.
Teratogenic Risk	First trimester: Increased risk of neural tube defects, cardiovascular anomalies, and oral clefts. Second and third trimesters: Associated with masculinization of female fetuses and potential for other congenital anomalies. Contraindicated in pregnancy.
Fetal Monitoring