Comparative Pharmacology
Head-to-head clinical analysis: LOESTRIN FE 1 5 30 versus LOESTRIN FE 1 20.
Peer-Reviewed Evidence
Head-to-head clinical analysis: LOESTRIN FE 1 5 30 versus LOESTRIN FE 1 20.
LOESTRIN FE 1.5/30 vs LOESTRIN FE 1/20
Head-to-head clinical comparison of therapeutic indices and safety profiles.
Suppresses gonadotropin (FSH and LH) release via estrogen and progestin feedback inhibition, preventing ovulation; increases cervical mucus viscosity and alters endometrial lining.
Combination oral contraceptive consisting of ethinyl estradiol and norethindrone acetate. Inhibits gonadotropin secretion (FSH, LH) via negative feedback on the hypothalamic-pituitary-ovarian axis, suppressing ovulation. Increases cervical mucus viscosity and alters endometrial structure, impeding sperm penetration and implantation.
Prevention of pregnancyTreatment of heavy menstrual bleeding (off-label)Treatment of dysmenorrhea (off-label)Treatment of acne (off-label)
Prevention of pregnancyTreatment of heavy menstrual bleeding (off-label)Treatment of acne (off-label)Treatment of dysmenorrhea (off-label)
One tablet orally once daily at the same time each day for 21 consecutive days, followed by 7 days of placebo (ferrous fumarate) tablets, then restart.
One tablet (norethindrone acetate 1 mg and ethinyl estradiol 20 mcg) orally once daily for 21 consecutive days, followed by one ferrous fumarate tablet (75 mg) orally once daily for 7 days.
None Documented
None Documented
Norethindrone: ~5-14 hours (terminal); Ethinyl estradiol: ~13-27 hours (terminal). Clinically, steady-state achieved within 5-7 days.
Norethindrone: 6-9 hours (terminal). Ethinyl estradiol: 13-27 hours (terminal, mean 16 hours). Steady-state reached within 5-7 days.
Metabolized in liver via CYP3A4 (norethindrone) and hydroxylation/conjugation (ethinyl estradiol).
Ethinyl estradiol: primarily metabolized by CYP3A4; undergoes sulfation and glucuronidation. Norethindrone: metabolized primarily by reduction and conjugation (CYP3A4 minor role). Both undergo enterohepatic recycling.
Renal: ~50-60% (norethindrone metabolites); Fecal: ~20-30% (norethindrone); Ethinyl estradiol: primarily renal (~40-50%) and fecal (~20-50%) as glucuronide and sulfate conjugates.
Norethindrone: 50-60% renal (as metabolites), 20-30% fecal. Ethinyl estradiol: 40-50% renal (as glucuronide conjugates), 30-40% fecal (as sulfate conjugates).
Norethindrone: ~80-90% bound to SHBG and albumin; Ethinyl estradiol: ~95-98% bound primarily to albumin (with some to SHBG).
Norethindrone: ~97% bound (mainly SHBG, also albumin). Ethinyl estradiol: ~98% bound (albumin, induces SHBG synthesis).
Norethindrone: ~4 L/kg; Ethinyl estradiol: ~4-10 L/kg; indicates extensive tissue distribution.
Norethindrone: 2-5 L/kg. Ethinyl estradiol: 2-4 L/kg (increased water solubility vs estradiol).
Oral: Norethindrone ~64%; Ethinyl estradiol ~38-48% (due to first-pass metabolism).
Norethindrone: 50-80% (oral). Ethinyl estradiol: 40-60% (oral, due to first-pass conjugation).
No dose adjustment required for renal impairment; however, use with caution in patients with impaired renal function due to potential fluid retention.
No dose adjustment required for mild to moderate renal impairment. Not studied in severe impairment (CrCl <30 mL/min); contraindicated in acute renal disease.
Contraindicated in acute hepatic disease or liver tumors (benign or malignant). For Child-Pugh Class A, no dose adjustment; avoid use in Class B or C.
Contraindicated in Child-Pugh class C. Use with caution in Child-Pugh class A or B; may increase risk of fluid retention and impaired metabolism.
Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults: one tablet orally once daily.
Not indicated for use before menarche. For postmenarchal adolescents: same dosing as adults (21 days active, 7 days ferrous fumarate).
Not indicated for use in postmenopausal women. No specific geriatric dosing.
Not indicated for use after menopause. If prescribed in perimenopause, use lowest effective dose due to increased risk of thromboembolic events and cardiovascular disease.
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use; risk increases with age and heavy smoking (≥15 cigarettes/day) and is significant in women over 35. Women who use combination oral contraceptives should be strongly advised not to smoke.
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age (especially women >35 years) and number of cigarettes smoked. Women >35 and who smoke should not use this product.
Increased risk of thromboembolic events; cardiovascular disease; hypertension; gallbladder disease; hepatic neoplasia; elevated liver enzymes; possible increased risk of breast/cervical cancer; glucose intolerance; fluid retention; hereditary angioedema; chloasma; irregular bleeding; depression; contact lens intolerance; possible reduced efficacy with enzyme-inducing drugs.
["Increased risk of thromboembolic disorders (e.g., DVT, PE, stroke, MI)","Cerebrovascular disease","Carcinoma of the breast and reproductive organs","Liver disease (hepatic adenoma, hepatocellular carcinoma)","Elevated blood pressure","Gallbladder disease","Carbohydrate/lipid metabolic effects","Hereditary angioedema","Chloasma","Ocular lesions (retinal thrombosis)","Depression","Reduced efficacy with concomitant enzyme inducers"]
Thrombophlebitis or thromboembolic disorders; history of deep vein thrombosis or pulmonary embolism; cerebrovascular or coronary artery disease; known or suspected breast carcinoma; carcinoma of endometrium or other estrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; cholestatic jaundice of pregnancy or jaundice with prior oral contraceptive use; hepatic adenoma or carcinoma; known or suspected pregnancy; hypersensitivity to any component; current or history of migraine with aura (age ≥35); heavy smoking (≥15 cigarettes/day) in women ≥35 years; uncontrolled hypertension; diabetes with vascular involvement; major surgery with prolonged immobilization; known thrombophilic conditions.
["Current or history of thrombosis (DVT, PE)","Cerebrovascular or coronary artery disease","Known or suspected breast cancer","Undiagnosed abnormal uterine bleeding","Known or suspected pregnancy","Liver neoplasia or active liver disease","Age >35 and smoking","Hypersensitivity to components"]
Data Pending Review
Data Pending Review
No significant food interactions. Grapefruit juice may slightly increase ethinyl estradiol levels but not clinically relevant. Separate iron tablets from high-calcium foods or supplements (e.g., dairy) to enhance iron absorption, but this does not affect contraceptive efficacy.
Avoid grapefruit and grapefruit juice as they may increase estrogen levels. No other significant food restrictions. The iron in the placebo tablets is best absorbed when taken with vitamin C (e.g., orange juice) but can be taken with food to reduce GI upset.
FDA Pregnancy Category X. Use contraindicated in pregnancy. First trimester: increased risk of neural tube defects, cardiovascular anomalies, and limb reduction defects. Second and third trimesters: associated with fetal harm, including masculinization of female fetuses due to progestin component. No safe use during pregnancy.
First trimester: Combination hormonal contraceptives are not associated with an increased risk of major birth defects when inadvertently taken. Second and third trimesters: No known risk of fetal abnormalities; however, use during pregnancy is not indicated. Postnatal: No evidence of long-term adverse effects from inadvertent exposure.
Small amounts of ethinyl estradiol and norethindrone acetate excreted in breast milk; M/P ratio not reported. May reduce milk production and quality. Use only if clearly needed; lowest effective dose recommended. Caution in nursing mothers.
Small amounts of ethinyl estradiol and progestins are excreted in human milk. M/P ratio not established. Use may reduce milk production, particularly with high-dose estrogen. Breastfeeding women should avoid combination hormonal contraceptives until weaning or use progestin-only methods.
Contraindicated in pregnancy; no dosing adjustment applicable. Discontinue immediately if pregnancy occurs.
No dose adjustment necessary as the drug is contraindicated during pregnancy. Pharmacokinetic changes in pregnancy (increased volume of distribution, altered hepatic metabolism) are not applicable as use is not recommended.
Category C
Category C
Loestrin Fe 1.5/30 contains norethindrone acetate 1.5 mg and ethinyl estradiol 30 mcg plus ferrous fumarate (75 mg) as placebo pills. The iron supplement does not affect contraceptive efficacy. Be aware of increased risk of venous thromboembolism, especially in smokers over 35. Use with caution in patients with migraine with aura. Drug interactions with CYP3A4 inducers (e.g., rifampin, carbamazepine) may reduce efficacy. Breakthrough bleeding is common in first few cycles. Do not use in patients with hepatic impairment or known thrombophilia.
Loestrin Fe 1/20 contains norethindrone acetate 1 mg, ethinyl estradiol 20 mcg, and ferrous fumarate (iron) as a placebo. The low estrogen dose (20 mcg) may increase breakthrough bleeding risk, especially in early cycles. Iron supplementation (75 mg ferrous fumarate) in the placebo phase helps maintain iron stores, which is beneficial for women with heavy menstrual bleeding. The progestin norethindrone acetate has mild androgenic activity, which may benefit libido but can worsen acne or hirsutism in susceptible women. Advise patients that the brown tablets (placebo) contain iron and should not be skipped. Contraindicated in patients with clotting disorders, migraines with aura (especially if age >35), smokers >35, history of breast cancer, or hepatic tumors.
Take one tablet daily at the same time each day, starting on the first day of menstrual bleeding.The first 21 tablets are active hormones; the last 7 tablets are iron supplements that do not prevent pregnancy.Missed dose: if you miss one active tablet, take it as soon as remembered; no backup needed. If you miss two, take two tablets and use backup contraception for 7 days.Iron tablets may cause dark stools; this is harmless.Report symptoms of blood clots: sudden leg pain, chest pain, shortness of breath, or severe headache.Use additional contraception if starting within 5 days of stopping another hormonal contraceptive.Avoid smoking while on this medication, especially if over 35.
Take one tablet daily at the same time each day. The first 24 white tablets are active hormones; the last 4 brown tablets are iron pills.You may experience spotting or breakthrough bleeding, especially in the first few months. Do not skip pills.This pill does not protect against HIV or other STIs. Use condoms for prevention.If you miss a white pill, take it as soon as remembered and continue the pack. If you miss 2 or more, use backup contraception for 7 days.The brown tablets contain iron; do not stop taking them even if you have bleeding.Common side effects include nausea, breast tenderness, headache, and mood changes. Report severe leg pain, chest pain, or vision changes immediately.Smoking while on this pill increases risk of blood clots, especially if over 35 years old.