NORLESTRIN FE 1/50

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NORLESTRIN FE 1/50 (NORLESTRIN FE 1/50).

How it works

Combination of ethinyl estradiol and norethindrone acetate provides negative feedback on gonadotropin release, suppressing ovulation. Also causes cervical mucus thickening and endometrial thinning.

What the body does with it

Metabolism	Norethindrone acetate: extensively metabolized via reduction (to active 5α-dihydro derivatives), hydroxylation, and conjugation; primarily by CYP3A4. Ethinyl estradiol: metabolized by CYP3A4 via hydroxylation and conjugation; undergoes enterohepatic circulation.
Excretion	Norethindrone: 20% renal, 80% fecal. Ethinyl estradiol: 40% renal, 60% fecal.
Half-life	Norethindrone: 5-12 hours (mean 8 hours). Ethinyl estradiol: 11-16 hours. Clinical context: Steady state reached in 5-7 days.
Protein binding	Norethindrone: 97% bound (albumin, SHBG). Ethinyl estradiol: 97% bound (albumin, SHBG, CBG).
Volume of Distribution	Norethindrone: 2-4 L/kg; Ethinyl estradiol: 2-4 L/kg; reflects tissue distribution.
Bioavailability	Oral: Norethindrone ~64%, Ethinyl estradiol ~38% (first-pass metabolism).
Onset of Action	Oral: Onset of contraceptive effect after 7 days of continuous use if started within 5 days of menses; otherwise, 7 days needed.
Duration of Action	Oral: 24 hours; missed pill guidelines: if missed >12 hours, consider backup contraception for 7 days.

Classification & Brands

Dosing & administration

One tablet (norethindrone 1 mg and ethinyl estradiol 50 mcg plus ferrous fumarate 75 mg) orally once daily for 28 days, with 21 active tablets and 7 placebo tablets.

Dosage form	TABLET
Renal impairment	No specific GFR-based dose modifications are recommended. Use with caution in patients with renal impairment or history of renal disease.
Liver impairment	Contraindicated in patients with hepatic impairment (Child-Pugh class A, B, or C) due to reduced clearance and risk of adverse effects.
Pediatric use	Not indicated in pediatric patients before menarche. In adolescents, dosing is the same as adults (one tablet daily). Safety and efficacy in post-menarcheal adolescents are similar to adults.
Geriatric use	Not indicated in geriatric patients. No specific dose adjustment; however, consider age-related risks (e.g., thromboembolism, cardiovascular disease). Use lowest effective dose if necessary.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for NORLESTRIN FE 1/50 (NORLESTRIN FE 1/50).

Breastfeeding	Excreted in breast milk in small amounts. M/P ratio not established. May reduce milk production and quality. Use is not recommended during breastfeeding. Consider alternative contraception.
Teratogenic Risk	Category X. Not indicated for use during pregnancy. First trimester: No increased risk of birth defects from inadvertent use; however, use is contraindicated. Second and third trimesters: Androgenic steroid exposure may cause feminization of male fetus, genital abnormalities, and potential long-term effects; no safe use established.

Warnings & precautions

■ FDA Black Box Warning

Cigarette smoking increases risk of serious cardiovascular events (e.g., stroke, myocardial infarction, thromboembolism) from combined hormonal contraceptive use, especially in women over 35 years who smoke.

Side Effect Profile

Serious Effects

Absolute Contraindications

Thrombophlebitis/venous thromboembolism (current or history), arterial thromboembolic disease (e.g., stroke, MI), cerebrovascular disease, coronary artery disease, valvular heart disease with complications, thrombogenic arrhythmias, diabetes with vascular involvement, severe hypertension, liver tumors or active liver disease, undiagnosed abnormal uterine bleeding, known or suspected pregnancy, breast cancer, hypersensitivity to components, jaundice with prior OC use, heavy smoking (>15 cigarettes/day) in women over 35.

Clinical Precautions

Precautions

Thrombotic disorders (DVT, PE, stroke, MI), hepatic neoplasia, gallbladder disease, carbohydrate/lipid effects, hypertension, hereditary angioedema, chloasma, retinal thrombosis (discontinue if sudden vision loss/proptosis/diplopia), depression.

Clinical Tips & Counseling

Drug interactions

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NORLESTRIN FE 1/50

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NORLESTRIN FE 1/50 (NORLESTRIN FE 1/50).

How it works

Combination of ethinyl estradiol and norethindrone acetate provides negative feedback on gonadotropin release, suppressing ovulation. Also causes cervical mucus thickening and endometrial thinning.

What the body does with it

Metabolism	Norethindrone acetate: extensively metabolized via reduction (to active 5α-dihydro derivatives), hydroxylation, and conjugation; primarily by CYP3A4. Ethinyl estradiol: metabolized by CYP3A4 via hydroxylation and conjugation; undergoes enterohepatic circulation.
Excretion	Norethindrone: 20% renal, 80% fecal. Ethinyl estradiol: 40% renal, 60% fecal.
Half-life	Norethindrone: 5-12 hours (mean 8 hours). Ethinyl estradiol: 11-16 hours. Clinical context: Steady state reached in 5-7 days.
Protein binding	Norethindrone: 97% bound (albumin, SHBG). Ethinyl estradiol: 97% bound (albumin, SHBG, CBG).
Volume of Distribution	Norethindrone: 2-4 L/kg; Ethinyl estradiol: 2-4 L/kg; reflects tissue distribution.
Bioavailability	Oral: Norethindrone ~64%, Ethinyl estradiol ~38% (first-pass metabolism).
Onset of Action	Oral: Onset of contraceptive effect after 7 days of continuous use if started within 5 days of menses; otherwise, 7 days needed.
Duration of Action	Oral: 24 hours; missed pill guidelines: if missed >12 hours, consider backup contraception for 7 days.

Classification & Brands

Dosing & administration

One tablet (norethindrone 1 mg and ethinyl estradiol 50 mcg plus ferrous fumarate 75 mg) orally once daily for 28 days, with 21 active tablets and 7 placebo tablets.

Dosage form	TABLET
Renal impairment	No specific GFR-based dose modifications are recommended. Use with caution in patients with renal impairment or history of renal disease.
Liver impairment	Contraindicated in patients with hepatic impairment (Child-Pugh class A, B, or C) due to reduced clearance and risk of adverse effects.
Pediatric use	Not indicated in pediatric patients before menarche. In adolescents, dosing is the same as adults (one tablet daily). Safety and efficacy in post-menarcheal adolescents are similar to adults.
Geriatric use	Not indicated in geriatric patients. No specific dose adjustment; however, consider age-related risks (e.g., thromboembolism, cardiovascular disease). Use lowest effective dose if necessary.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for NORLESTRIN FE 1/50 (NORLESTRIN FE 1/50).

Breastfeeding	Excreted in breast milk in small amounts. M/P ratio not established. May reduce milk production and quality. Use is not recommended during breastfeeding. Consider alternative contraception.
Teratogenic Risk	Category X. Not indicated for use during pregnancy. First trimester: No increased risk of birth defects from inadvertent use; however, use is contraindicated. Second and third trimesters: Androgenic steroid exposure may cause feminization of male fetus, genital abnormalities, and potential long-term effects; no safe use established.