LOESTRIN 21 1/20

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LOESTRIN 21 1/20 (LOESTRIN 21 1/20).

How it works

Combination estrogen-progestin contraceptive; suppresses gonadotropin secretion (FSH, LH) via negative feedback, inhibiting ovulation; increases cervical mucus viscosity and alters endometrial receptivity.

What the body does with it

Metabolism	Ethinyl estradiol is metabolized primarily by CYP3A4; norethindrone is metabolized by CYP3A4 and reduction, conjugation (sulfation and glucuronidation).
Excretion	Renal: ~50% (as metabolites, primarily glucuronide conjugates of norethindrone and ethinyl estradiol); Fecal: ~35% (via bile); Urinary recovery of unchanged drug is minimal (<1%).
Half-life	Norethindrone: 8-11 hours (terminal half-life; steady-state achieved after 5-10 days); Ethinyl estradiol: 13-27 hours (terminal half-life; significant interindividual variability due to enterohepatic recirculation).
Protein binding	Norethindrone: ~61% bound to albumin and SHBG; Ethinyl estradiol: ~97-98% bound to albumin (not to SHBG).
Volume of Distribution	Norethindrone: 2-4 L/kg; Ethinyl estradiol: 2-4 L/kg (indicating extensive tissue distribution and high lipophilicity).
Bioavailability	Oral: Norethindrone ~64% (due to first-pass metabolism); Ethinyl estradiol ~45% (range 30-60%, with significant first-pass conjugation to sulfate and glucuronide).
Onset of Action	Oral: Contraceptive effect requires 7 days of continuous dosing to reliably inhibit ovulation (start on day 1 of menses for immediate effect; if started later, use backup contraception for 7 days).
Duration of Action	Oral: 24 hours (once-daily dosing maintains contraceptive efficacy; missed pill increases risk of ovulation, especially if >12 hours late).

Classification & Brands

Dosing & administration

One tablet orally once daily for 21 days, then 7 days off. Each tablet contains norethindrone acetate 1 mg and ethinyl estradiol 20 mcg.

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 fluid retention.
Liver impairment	Contraindicated in Child-Pugh class B and C (moderate to severe hepatic impairment). For Child-Pugh class A, use with caution; consider alternative contraception.
Pediatric use	Not indicated for use before menarche. Post-menarche: same as adult dosing (one tablet daily for 21 days, 7 days off).
Geriatric use	Not indicated for postmenopausal women. No specific geriatric dosing studies; use lowest effective dose if considered, but generally avoid due to increased thromboembolic risk.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LOESTRIN 21 1/20 (LOESTRIN 21 1/20).

Breastfeeding	Excreted in breast milk. Estrogen and progestin may reduce milk production and quality. M/P ratio not established. Use during breastfeeding not recommended. Alternative contraception advised until weaning.
Teratogenic Risk	Pregnancy category X. Contraindicated in pregnancy. Use during first trimester associated with cardiovascular defects, limb reduction defects, and neural tube defects. Exposure in second and third trimester increases risk of fetal feminization in male fetuses, vaginal adenosis and cervical cancer in female fetuses. No known risk in third trimester for congenital anomalies.

Warnings & precautions

■ FDA Black Box Warning

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

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known or suspected pregnancy","Current or past history of thromboembolic disorders or cerebrovascular disease","Significant liver disease or liver tumors (benign or malignant)","Known or suspected estrogen-dependent neoplasia (e.g., breast cancer)","Undiagnosed abnormal uterine bleeding","Hypersensitivity to any component","Headache with focal neurological symptoms (e.g., migraine with aura) in women >35 years","Cigarette smoking in women >35 years"]

Clinical Precautions

Precautions

["Increased risk of thromboembolic disorders (e.g., DVT, PE, stroke, MI)","Hepatic neoplasia risk","Ocular lesions (e.g., retinal thrombosis)","Carbohydrate metabolism alterations","Elevated blood pressure","Gallbladder disease","Depression","Interactions with enzyme-inducing drugs (e.g., rifampin, anticonvulsants)"]

Clinical Tips & Counseling

Drug interactions

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LOESTRIN 21 1/20

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LOESTRIN 21 1/20 (LOESTRIN 21 1/20).

How it works

What the body does with it

Metabolism	Ethinyl estradiol is metabolized primarily by CYP3A4; norethindrone is metabolized by CYP3A4 and reduction, conjugation (sulfation and glucuronidation).
Excretion	Renal: ~50% (as metabolites, primarily glucuronide conjugates of norethindrone and ethinyl estradiol); Fecal: ~35% (via bile); Urinary recovery of unchanged drug is minimal (<1%).
Half-life	Norethindrone: 8-11 hours (terminal half-life; steady-state achieved after 5-10 days); Ethinyl estradiol: 13-27 hours (terminal half-life; significant interindividual variability due to enterohepatic recirculation).
Protein binding	Norethindrone: ~61% bound to albumin and SHBG; Ethinyl estradiol: ~97-98% bound to albumin (not to SHBG).
Volume of Distribution	Norethindrone: 2-4 L/kg; Ethinyl estradiol: 2-4 L/kg (indicating extensive tissue distribution and high lipophilicity).
Bioavailability	Oral: Norethindrone ~64% (due to first-pass metabolism); Ethinyl estradiol ~45% (range 30-60%, with significant first-pass conjugation to sulfate and glucuronide).
Onset of Action	Oral: Contraceptive effect requires 7 days of continuous dosing to reliably inhibit ovulation (start on day 1 of menses for immediate effect; if started later, use backup contraception for 7 days).
Duration of Action	Oral: 24 hours (once-daily dosing maintains contraceptive efficacy; missed pill increases risk of ovulation, especially if >12 hours late).

Classification & Brands

Dosing & administration

One tablet orally once daily for 21 days, then 7 days off. Each tablet contains norethindrone acetate 1 mg and ethinyl estradiol 20 mcg.

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 fluid retention.
Liver impairment	Contraindicated in Child-Pugh class B and C (moderate to severe hepatic impairment). For Child-Pugh class A, use with caution; consider alternative contraception.
Pediatric use	Not indicated for use before menarche. Post-menarche: same as adult dosing (one tablet daily for 21 days, 7 days off).
Geriatric use	Not indicated for postmenopausal women. No specific geriatric dosing studies; use lowest effective dose if considered, but generally avoid due to increased thromboembolic risk.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LOESTRIN 21 1/20 (LOESTRIN 21 1/20).

Breastfeeding	Excreted in breast milk. Estrogen and progestin may reduce milk production and quality. M/P ratio not established. Use during breastfeeding not recommended. Alternative contraception advised until weaning.
Teratogenic Risk	Pregnancy category X. Contraindicated in pregnancy. Use during first trimester associated with cardiovascular defects, limb reduction defects, and neural tube defects. Exposure in second and third trimester increases risk of fetal feminization in male fetuses, vaginal adenosis and cervical cancer in female fetuses. No known risk in third trimester for congenital anomalies.