LO LOESTRIN FE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LO LOESTRIN FE (LO LOESTRIN FE).

How it works

Combination of ethinyl estradiol and norethindrone acetate suppresses gonadotropin-releasing hormone (GnRH) from the hypothalamus, reducing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary, thereby inhibiting ovulation. The progestin component thickens cervical mucus, impeding sperm penetration, and alters endometrial receptivity. Ferrous fumarate provides supplemental iron.

What the body does with it

Metabolism	Ethinyl estradiol is metabolized primarily via CYP3A4, with hydroxylation and conjugation pathways. Norethindrone acetate is rapidly hydrolyzed to norethindrone, which is metabolized via reduction and conjugation. Ferrous fumarate is absorbed and utilized for hemoglobin synthesis.
Excretion	Renal (primarily as glucuronide conjugates of norethindrone and ethinyl estradiol): ~40% norethindrone metabolites, ~30% ethinyl estradiol metabolites; Fecal: ~30% norethindrone metabolites, ~40% ethinyl estradiol metabolites.
Half-life	Norethindrone: ~8 hours (range 5–12 h); Ethinyl estradiol: ~14 hours (range 10–20 h). Terminal half-life supports once-daily dosing with steady-state reached within 7–14 days.
Protein binding	Norethindrone: ~61% bound (primarily to albumin and SHBG); Ethinyl estradiol: ~97–98% bound (primarily to albumin, with ~1–2% free).
Volume of Distribution	Norethindrone: ~4 L/kg; Ethinyl estradiol: ~3–4 L/kg. Indicates extensive tissue distribution consistent with lipophilic steroids.
Bioavailability	Norethindrone: ~64% (oral); Ethinyl estradiol: ~45% (oral) due to first-pass metabolism, with high interindividual variability.
Onset of Action	Oral: Contraceptive effect requires 7 consecutive days of active tablets; initial suppression of ovulation begins within first cycle. Peak plasma concentrations: norethindrone ~1–2 h, ethinyl estradiol ~1.5–2 h post-dose.
Duration of Action	Contraceptive effect persists for 22 days of active therapy; 2 days of placebo with withdrawal bleed; 6 days of iron supplements. Duration of action is drug-dependent and supports daily dosing schedule.

Classification & Brands

Dosing & administration

One tablet orally once daily. Each tablet contains norethindrone acetate 1 mg and ethinyl estradiol 10 mcg (24 active tablets) followed by ferrous fumarate 75 mg (2 inactive tablets).

Dosage form	TABLET
Renal impairment	No specific dosage adjustment required for renal impairment. Use with caution in patients with renal dysfunction due to potential fluid retention.
Liver impairment	Contraindicated in patients with hepatic impairment, including acute or chronic liver disease, hepatic adenomas, or impaired liver function. No adjustment guidelines available; do not use.
Pediatric use	Not indicated for use before menarche. For post-menarchal adolescents, same dosing as adults: one tablet orally once daily.
Geriatric use	Not indicated for use in postmenopausal women. No specific dosing adjustments for elderly patients as the drug is not used in this population.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LO LOESTRIN FE (LO LOESTRIN FE).

Breastfeeding	Excreted in breast milk in small amounts; no reported adverse effects in infants. M/P ratio for ethinyl estradiol is approximately 0.04. Use with caution, especially during early postpartum period due to potential effects on milk production.
Teratogenic Risk	Pregnancy category X. Contraindicated in pregnant women due to risk of fetal harm, including cardiovascular defects and neural tube defects. Use during first trimester associated with oral clefts; second and third trimester use may lead to fetal hyperbilirubinemia and jaundice.

Warnings & precautions

■ FDA Black Box Warning

Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use this product.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Current or history of thrombophlebitis, DVT, or thromboembolic disorders","Cerebrovascular or coronary artery disease","Known or suspected pregnancy","Undiagnosed abnormal uterine bleeding","Breast carcinoma or other hormone-sensitive cancer","Hepatic tumor (benign or malignant) or active liver disease","Hypersensitivity to any component","Smoking in women over 35","Hemochromatosis or chronic hemolytic anemia (due to ferrous fumarate)"]

Clinical Precautions

Precautions

["Increased risk of venous thromboembolism (VTE), myocardial infarction, and stroke, especially in smokers and women with hypertension or migraines","Adverse effects on bone density and potential for fractures with long-term use","Hepatic adenoma or hepatocellular carcinoma risk","Gallbladder disease","Glucose intolerance and insulin resistance","Elevated blood pressure","Cholestatic jaundice","Ocular lesions (e.g., retinal thrombosis)","Depression","Iron overload in patients with hemochromatosis or chronic hemolytic anemia (due to ferrous fumarate)"]

Clinical Tips & Counseling

Drug interactions

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LO LOESTRIN FE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LO LOESTRIN FE (LO LOESTRIN FE).

How it works

What the body does with it

Metabolism	Ethinyl estradiol is metabolized primarily via CYP3A4, with hydroxylation and conjugation pathways. Norethindrone acetate is rapidly hydrolyzed to norethindrone, which is metabolized via reduction and conjugation. Ferrous fumarate is absorbed and utilized for hemoglobin synthesis.
Excretion	Renal (primarily as glucuronide conjugates of norethindrone and ethinyl estradiol): ~40% norethindrone metabolites, ~30% ethinyl estradiol metabolites; Fecal: ~30% norethindrone metabolites, ~40% ethinyl estradiol metabolites.
Half-life	Norethindrone: ~8 hours (range 5–12 h); Ethinyl estradiol: ~14 hours (range 10–20 h). Terminal half-life supports once-daily dosing with steady-state reached within 7–14 days.
Protein binding	Norethindrone: ~61% bound (primarily to albumin and SHBG); Ethinyl estradiol: ~97–98% bound (primarily to albumin, with ~1–2% free).
Volume of Distribution	Norethindrone: ~4 L/kg; Ethinyl estradiol: ~3–4 L/kg. Indicates extensive tissue distribution consistent with lipophilic steroids.
Bioavailability	Norethindrone: ~64% (oral); Ethinyl estradiol: ~45% (oral) due to first-pass metabolism, with high interindividual variability.
Onset of Action	Oral: Contraceptive effect requires 7 consecutive days of active tablets; initial suppression of ovulation begins within first cycle. Peak plasma concentrations: norethindrone ~1–2 h, ethinyl estradiol ~1.5–2 h post-dose.
Duration of Action	Contraceptive effect persists for 22 days of active therapy; 2 days of placebo with withdrawal bleed; 6 days of iron supplements. Duration of action is drug-dependent and supports daily dosing schedule.

Classification & Brands

Dosing & administration

One tablet orally once daily. Each tablet contains norethindrone acetate 1 mg and ethinyl estradiol 10 mcg (24 active tablets) followed by ferrous fumarate 75 mg (2 inactive tablets).

Dosage form	TABLET
Renal impairment	No specific dosage adjustment required for renal impairment. Use with caution in patients with renal dysfunction due to potential fluid retention.
Liver impairment	Contraindicated in patients with hepatic impairment, including acute or chronic liver disease, hepatic adenomas, or impaired liver function. No adjustment guidelines available; do not use.
Pediatric use	Not indicated for use before menarche. For post-menarchal adolescents, same dosing as adults: one tablet orally once daily.
Geriatric use	Not indicated for use in postmenopausal women. No specific dosing adjustments for elderly patients as the drug is not used in this population.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LO LOESTRIN FE (LO LOESTRIN FE).

Breastfeeding	Excreted in breast milk in small amounts; no reported adverse effects in infants. M/P ratio for ethinyl estradiol is approximately 0.04. Use with caution, especially during early postpartum period due to potential effects on milk production.
Teratogenic Risk	Pregnancy category X. Contraindicated in pregnant women due to risk of fetal harm, including cardiovascular defects and neural tube defects. Use during first trimester associated with oral clefts; second and third trimester use may lead to fetal hyperbilirubinemia and jaundice.