ORTHO TRI-CYCLEN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ORTHO TRI-CYCLEN (ORTHO TRI-CYCLEN).

How it works

Combined estrogen-progestin oral contraceptive; suppresses gonadotropin release, inhibiting ovulation; increases cervical mucus viscosity and alters endometrial lining.

What the body does with it

Metabolism	Ethinyl estradiol: primarily metabolized by CYP3A4; norgestimate: rapidly hydrolyzed to norelgestromin (active) then levonorgestrel, metabolized by CYP3A4 and CYP2C9.
Excretion	Norethindrone: 60-80% renal (as metabolites), 20-40% fecal. Ethinyl estradiol: ~40% renal, ~60% fecal. Biliary excretion contributes to fecal elimination.
Half-life	Norethindrone: ~8 hours (terminal). Ethinyl estradiol: ~12-15 hours (terminal). Clinical context: Steady-state achieved within 5-7 days; contraceptive efficacy maintained with daily dosing.
Protein binding	Norethindrone: ~97% bound to albumin and SHBG. Ethinyl estradiol: ~98% bound to albumin.
Volume of Distribution	Norethindrone: 3-4 L/kg (large distribution into tissues, including breast and reproductive tissues). Ethinyl estradiol: 2-3 L/kg (distributes widely).
Bioavailability	Norethindrone: ~65% (oral). Ethinyl estradiol: ~40-45% (oral) due to first-pass metabolism.
Onset of Action	Oral: 7 days of continuous dosing required for full contraceptive effect; initial suppression of ovulation occurs within 2-3 days.
Duration of Action	24 hours with daily dosing; inhibition of ovulation persists for the length of the dosing cycle; missed doses increase risk of ovulation within 48 hours.

Classification & Brands

Dosing & administration

One tablet (norgestimate 0.180-0.215-0.250 mg/ethinyl estradiol 0.035 mg) orally once daily for 21 days, followed by 7 days of placebo or no tablets.

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 alternative contraception.
Liver impairment	Contraindicated in patients with acute hepatitis, cholestatic jaundice of pregnancy or prior OCP use, or severe cirrhosis (Child-Pugh C). Use with caution in Child-Pugh A/B; dose adjustment not defined but consider lower estrogen options.
Pediatric use	Not indicated in prepubertal children. Postmenarchal adolescents: same dosing as adults. Safety and efficacy not established in children <18 years.
Geriatric use	Not indicated for use after menopause. No specific geriatric dosing; contraindicated in postmenopausal women.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ORTHO TRI-CYCLEN (ORTHO TRI-CYCLEN).

Breastfeeding	Small amounts of ethinyl estradiol and norgestimate pass into breast milk; may reduce milk production and composition. M/P ratio not established. Generally avoided during breastfeeding; alternative contraception recommended.
Teratogenic Risk	Contraindicated in pregnancy. First trimester: associated with cardiovascular defects and limb reduction defects. Second and third trimesters: no increased risk of major malformations, but may cause fetal harm due to hormonal effects; use only if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

Cigarette smoking increases risk of serious cardiovascular events from combined hormonal contraceptive use. Risk increases with age and number of cigarettes smoked, especially in women over 35.

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","Pregnancy","Active liver disease or benign/malignant liver tumors","Hypersensitivity to any component","Heavy smoking in women over 35"]

Clinical Precautions

Precautions

["Thrombotic disorders (venous thromboembolism, stroke, myocardial infarction)","Hepatic neoplasia (benign/malignant)","Gallbladder disease","Hypertension","Carbohydrate/lipid effects","Hereditary angioedema","Chloasma","Retinal thrombosis","Depression"]

Clinical Tips & Counseling

Drug interactions

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ORTHO TRI-CYCLEN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ORTHO TRI-CYCLEN (ORTHO TRI-CYCLEN).

How it works

Combined estrogen-progestin oral contraceptive; suppresses gonadotropin release, inhibiting ovulation; increases cervical mucus viscosity and alters endometrial lining.

What the body does with it

Metabolism	Ethinyl estradiol: primarily metabolized by CYP3A4; norgestimate: rapidly hydrolyzed to norelgestromin (active) then levonorgestrel, metabolized by CYP3A4 and CYP2C9.
Excretion	Norethindrone: 60-80% renal (as metabolites), 20-40% fecal. Ethinyl estradiol: ~40% renal, ~60% fecal. Biliary excretion contributes to fecal elimination.
Half-life	Norethindrone: ~8 hours (terminal). Ethinyl estradiol: ~12-15 hours (terminal). Clinical context: Steady-state achieved within 5-7 days; contraceptive efficacy maintained with daily dosing.
Protein binding	Norethindrone: ~97% bound to albumin and SHBG. Ethinyl estradiol: ~98% bound to albumin.
Volume of Distribution	Norethindrone: 3-4 L/kg (large distribution into tissues, including breast and reproductive tissues). Ethinyl estradiol: 2-3 L/kg (distributes widely).
Bioavailability	Norethindrone: ~65% (oral). Ethinyl estradiol: ~40-45% (oral) due to first-pass metabolism.
Onset of Action	Oral: 7 days of continuous dosing required for full contraceptive effect; initial suppression of ovulation occurs within 2-3 days.
Duration of Action	24 hours with daily dosing; inhibition of ovulation persists for the length of the dosing cycle; missed doses increase risk of ovulation within 48 hours.

Classification & Brands

Dosing & administration

One tablet (norgestimate 0.180-0.215-0.250 mg/ethinyl estradiol 0.035 mg) orally once daily for 21 days, followed by 7 days of placebo or no tablets.

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 alternative contraception.
Liver impairment	Contraindicated in patients with acute hepatitis, cholestatic jaundice of pregnancy or prior OCP use, or severe cirrhosis (Child-Pugh C). Use with caution in Child-Pugh A/B; dose adjustment not defined but consider lower estrogen options.
Pediatric use	Not indicated in prepubertal children. Postmenarchal adolescents: same dosing as adults. Safety and efficacy not established in children <18 years.
Geriatric use	Not indicated for use after menopause. No specific geriatric dosing; contraindicated in postmenopausal women.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ORTHO TRI-CYCLEN (ORTHO TRI-CYCLEN).

Breastfeeding	Small amounts of ethinyl estradiol and norgestimate pass into breast milk; may reduce milk production and composition. M/P ratio not established. Generally avoided during breastfeeding; alternative contraception recommended.
Teratogenic Risk	Contraindicated in pregnancy. First trimester: associated with cardiovascular defects and limb reduction defects. Second and third trimesters: no increased risk of major malformations, but may cause fetal harm due to hormonal effects; use only if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

Cigarette smoking increases risk of serious cardiovascular events from combined hormonal contraceptive use. Risk increases with age and number of cigarettes smoked, especially in women over 35.