Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
NORTREL 0.5/35-28 vs ALTAVERA
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Norethindrone and ethinyl estradiol are a combination hormonal contraceptive. Norethindrone suppresses gonadotropin release (FSH and LH) from the pituitary, inhibiting ovulation. Ethinyl estradiol stabilizes the endometrium and enhances the contraceptive effect by inhibiting gonadotropin secretion.
Combination of ethinyl estradiol and desogestrel: ethinyl estradiol suppresses gonadotropin release, inhibiting ovulation; desogestrel (progestin) causes cervical mucus thickening and endometrial atrophy, preventing implantation.
Prevention of pregnancy,Oral contraceptive (off-label: treatment of acne, abnormal uterine bleeding, dysmenorrhea)
Prevention of pregnancy,Treatment of moderate acne vulgaris (in females ≥15 years with no contraindications)
1 tablet orally once daily for 28 days (21 active tablets containing 0.5 mg norethindrone and 35 mcg ethinyl estradiol, followed by 7 placebo tablets).
1 tablet (ethinyl estradiol 0.03 mg / levonorgestrel 0.15 mg) orally once daily for 21 days, followed by 7 placebo days.
Norethindrone: 7.2-9.2 hours; Ethinyl estradiol: 13-27 hours. Clinical context: Steady state reached in 5-7 days; half-life supports once-daily dosing.
Levonorgestrel: terminal elimination half-life 25±10 hours; ethinyl estradiol: 13±7 hours. Clinical context: steady-state concentrations achieved within 5-7 days; contraceptive efficacy requires consistent daily dosing.
Norethindrone: primarily hepatic via reduction and sulfation; CYP3A4 involved. Ethinyl estradiol: hepatic via CYP3A4; undergoes first-pass metabolism and enterohepatic recirculation.
Ethinyl estradiol: primarily metabolized by CYP3A4; undergoes sulfation and glucuronidation. Desogestrel: rapidly converted to active metabolite etonogestrel via CYP2C9 and CYP2C19; further metabolism by CYP3A4.
Renal: ~40% as metabolites; Biliary/Fecal: ~60% as metabolites; <5% unchanged.
Renal excretion of metabolites and unchanged drug: ~30% (levonorgestrel) and ~20% (ethinyl estradiol) in urine; biliary/fecal elimination: ~40-50% as conjugates and metabolites.
Norethindrone: 61% bound to albumin, 36% to SHBG; Ethinyl estradiol: 97% bound to albumin, 2% free.
Levonorgestrel: 98-99% bound to sex hormone-binding globulin (SHBG) and albumin; ethinyl estradiol: 98% bound to albumin.
Norethindrone: 3.6-4.3 L/kg; Ethinyl estradiol: 2.3-3.7 L/kg; indicates extensive tissue distribution.
Levonorgestrel: Vd ~1.8 L/kg (suggesting extensive tissue distribution). Ethinyl estradiol: Vd ~2.4 L/kg.
Oral: Norethindrone ~64% (extensive first-pass metabolism); Ethinyl estradiol ~43-45% (due to first-pass and gut wall metabolism).
Oral bioavailability: levonorgestrel ~100% (nearly complete); ethinyl estradiol ~45-50% (first-pass hepatic metabolism).
No dose adjustment required for GFR ≥30 m L/min. Use is not recommended in patients with GFR <30 m L/min or on dialysis due to potential decrease in hormone clearance and increased risk of adverse effects.
No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal disease or acute renal failure due to potential fluid retention.
Contraindicated in patients with Child-Pugh class B or C hepatic impairment. For Child-Pugh class A, use is not recommended due to potential reduced hormone metabolism.
Contraindicated in severe hepatic dysfunction (Child-Pugh class B or C). Use caution in mild to moderate impairment (Child-Pugh A); monitor liver enzymes.
Not indicated for use in pediatric patients before menarche. For post-menarcheal adolescents, dosing is same as adults: 1 tablet orally once daily for 28 days.
Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults (1 tablet daily, 21/7 regimen) after evaluation of risks.
Not indicated for use in postmenopausal women. No specific dosing adjustments for elderly patients as the drug is not used in this population for contraception.
Not indicated for postmenopausal women. No specific geriatric dosing; consider increased risk of thromboembolism, cardiovascular disease, and metabolic effects in older women of reproductive age.
Cigarette smoking increases the risk of serious cardiovascular events from combined hormonal contraceptive use. The risk increases with age and heavy smoking (≥15 cigarettes per day) and is significant in women over 35 years old. Women over 35 who smoke should not use combined hormonal contraceptives.
Cigarette smoking increases risk of serious cardiovascular events from combined oral contraceptives. Risk increases with age (especially >35 years) and with number of cigarettes smoked. Women who use combined hormonal contraceptives should be strongly advised not to smoke.
Increased risk of thrombotic disorders (venous thromboembolism, stroke, myocardial infarction),Hepatic neoplasia (benign and malignant),Elevated blood pressure,Gallbladder disease,Carbohydrate/lipid metabolism effects,Headache/migraine,Irregular bleeding,Ocular changes (retinal thrombosis),Depression,Hereditary angioedema,Pregnancy (discontinue if pregnancy occurs)
Thrombotic disorders: risk of venous thromboembolism (VTE), stroke, myocardial infarction; discontinue if thrombotic event occurs.,Hepatic disease: discontinue if jaundice or liver function abnormalities develop.,Hypertension: monitor blood pressure; discontinue if uncontrolled.,Carbohydrate metabolism: may affect glucose tolerance; monitor diabetic patients.,Depression: discontinue if significant depression occurs.,Gallbladder disease: increased risk of cholelithiasis.
Known or suspected pregnancy,Current or history of venous thrombotic disease (deep vein thrombosis, pulmonary embolism),Cerebrovascular or coronary artery disease,Current or history of migraine with aura (if age ≥35),Breast cancer or other estrogen-sensitive neoplasia,Undiagnosed abnormal genital bleeding,Cholestatic jaundice of pregnancy or jaundice with prior oral contraceptive use,Active liver disease or benign/malignant liver tumors,Hypersensitivity to any component,Smoking cigarettes and age >35 years
Thrombophlebitis or thromboembolic disorders (current or history),Cerebrovascular or coronary artery disease (current or history),Known or suspected breast carcinoma,Estrogen-dependent neoplasia (known or suspected),Undiagnosed abnormal genital bleeding,Cholestatic jaundice of pregnancy or jaundice with prior pill use,Hepatic adenoma or carcinoma (known or suspected),Pregnancy (known or suspected),Hypersensitivity to any component
No specific food restrictions. Grapefruit juice may increase ethinyl estradiol levels; avoid large amounts. Alcohol may increase risk of liver toxicity; limit intake.
No significant food interactions. Alcohol does not affect efficacy but may increase risk of adverse effects such as nausea. Grapefruit juice has no known interaction. Avoid excessive alcohol consumption due to potential hepatotoxicity.
First trimester: No increased risk of major birth defects based on large cohort studies. Second and third trimesters: Associated with masculinization of female fetuses (clitoral hypertrophy, labial fusion) and possible altered pubertal development. Risk of pseudohermaphroditism is dose-dependent.
ALTAVERA contains ethinyl estradiol and levonorgestrel. First trimester: Inadvertent exposure during organogenesis is associated with a very low absolute risk of cardiovascular defects (relative risk 1.2-1.4) and no consistent increase in other major malformations. Second and third trimesters: No known teratogenic effects, but theoretical risks from estrogenic effects (e.g., feminization of male fetus). Postnatal: No increased risk of long-term developmental effects from pregnancy exposure.
Norethindrone and ethinyl estradiol are excreted in breast milk. Estrogen components may reduce milk production. M/P ratio for norethindrone is approximately 0.7; ethinyl estradiol is <1. Use is generally not recommended during lactation.
Combined oral contraceptives may reduce milk production and quality, especially in early lactation. Ethinyl estradiol transfers into breast milk at low levels (M/P ratio approximately 0.1-0.2), excluding clinical effects in term infants. Levonorgestrel transfer is minimal (M/P ratio ~0.2-0.4). Use is generally avoided in breastfeeding women, especially during the first 6 weeks postpartum. Progestin-only methods are preferred.
Contraindicated in pregnancy; no dose adjustments recommended. Discontinue immediately if pregnancy occurs.
Contraindicated in pregnancy. No dose adjustment recommended because use is discontinued upon confirmed or suspected pregnancy. Pharmacokinetic changes in pregnancy (e.g., increased hepatic clearance, altered binding proteins) are not relevant for this indication.
NORTREL 0.5/35-28 is a monophasic combined oral contraceptive containing 0.5 mg norethindrone and 35 mcg ethinyl estradiol. Administer daily at the same time. Breakthrough bleeding is common in the first 3-6 months. Monitor blood pressure at baseline and annually. Consider VTE risk in smokers over 35. Missed pill protocol: if one pill is missed, take as soon as remembered; if two or more, use backup contraception for 7 days.
ALTAVERA is a combined oral contraceptive (COC) containing ethinylestradiol and levonorgestrel. It inhibits ovulation via suppression of gonadotropins. Counsel patients to take at the same time daily to maintain efficacy. Missed pill management: if missed within 12 hours, take immediately; if >12 hours, take last missed pill and use backup contraception for 7 days. Be aware of increased VTE risk, especially in smokers over 35. May reduce effectiveness of lamotrigine; monitor seizure control. Initiate on the first day of menses or first Sunday after onset.
Take one pill daily at the same time, in the order shown on the blister pack.,If you miss a pill, follow the package insert instructions and use backup contraception if needed.,Common side effects include nausea, breast tenderness, and spotting between periods.,Do not smoke while taking this medication, especially if over 35 years old.,Report symptoms of blood clots, including leg pain/swelling, chest pain, or sudden shortness of breath.,This medication does not protect against HIV or other sexually transmitted infections.
Take one tablet daily at the same time each day, with or without food.,If you miss a pill by less than 12 hours, take it as soon as you remember. If more than 12 hours, take the missed pill and use a backup method (e.g., condoms) for the next 7 days.,Smoking increases your risk of serious cardiovascular side effects, especially if you are over 35 years old. Do not smoke while taking this medication.,Seek immediate medical attention if you experience sudden severe headache, chest pain, leg pain/swelling, or vision changes (symptoms of blood clots).,This medication does not protect against HIV or other sexually transmitted infections.,If you are taking lamotrigine or other anticonvulsants, tell your doctor; your seizure medication may be less effective.,Store at room temperature away from moisture and heat.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about NORTREL 0.5/35-28 vs ALTAVERA, answered by our medical review team.
NORTREL 0.5/35-28 is a Oral Contraceptive that works by Norethindrone and ethinyl estradiol are a combination hormonal contraceptive. Norethindrone suppresses gonadotropin release (FSH and LH) from the pituitary, inhibiting ovulation. Ethinyl estradiol stabilizes the endometrium and enhances the contraceptive effect by inhibiting gonadotropin secretion.. ALTAVERA is a Combined Oral Contraceptive that works by Combination of ethinyl estradiol and desogestrel: ethinyl estradiol suppresses gonadotropin release, inhibiting ovulation; desogestrel (progestin) causes cervical mucus thickening and endometrial atrophy, preventing implantation.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between NORTREL 0.5/35-28 and ALTAVERA depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of NORTREL 0.5/35-28 is: 1 tablet orally once daily for 28 days (21 active tablets containing 0.5 mg norethindrone and 35 mcg ethinyl estradiol, followed by 7 placebo tablets).. The standard adult dose of ALTAVERA is: 1 tablet (ethinyl estradiol 0.03 mg / levonorgestrel 0.15 mg) orally once daily for 21 days, followed by 7 placebo days.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between NORTREL 0.5/35-28 and ALTAVERA in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. NORTREL 0.5/35-28 is classified as Category C. First trimester: No increased risk of major birth defects based on large cohort studies. Second and third trimesters: Associated with masculinization of female fetuses (clitoral hy. ALTAVERA is classified as Category C. ALTAVERA contains ethinyl estradiol and levonorgestrel. First trimester: Inadvertent exposure during organogenesis is associated with a very low absolute risk of cardiovascular def. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.