Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
NORTREL 1/35-28 vs ALTAVERA
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Combination of ethinyl estradiol and norethindrone inhibits gonadotropin secretion via negative feedback on the hypothalamic-pituitary-ovarian axis, suppressing ovulation. Additionally, increases cervical mucus viscosity and alters endometrial receptivity.
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
Prevention of pregnancy,Treatment of moderate acne vulgaris (in females ≥15 years with no contraindications)
One tablet (norethindrone 1 mg + ethinyl estradiol 35 mcg) orally once daily for 28 days, followed by a 7-day placebo period (if using 28-day pack) or continuous if using 21-day pack with 7-day off. Start on first day of menstrual period.
1 tablet (ethinyl estradiol 0.03 mg / levonorgestrel 0.15 mg) orally once daily for 21 days, followed by 7 placebo days.
Norethindrone: 5-14 hours (terminal); ethinyl estradiol: 13-27 hours (terminal). Context: steady-state after 5-7 days; dose adjustment in hepatic impairment.
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.
Primarily hepatic via CYP3A4; ethinyl estradiol undergoes first-pass metabolism; norethindrone is metabolized via reduction and conjugation.
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 60-70% (as glucuronide and sulfate conjugates), fecal 20-30% (via biliary excretion).
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: 99% bound (SHBG, albumin); ethinyl estradiol: 98% bound (albumin, SHBG).
Levonorgestrel: 98-99% bound to sex hormone-binding globulin (SHBG) and albumin; ethinyl estradiol: 98% bound to albumin.
Norethindrone: 4-5 L/kg (extensive tissue distribution); ethinyl estradiol: 2-4 L/kg (significant tissue uptake).
Levonorgestrel: Vd ~1.8 L/kg (suggesting extensive tissue distribution). Ethinyl estradiol: Vd ~2.4 L/kg.
Norethindrone: 47-73% (oral); ethinyl estradiol: 38-48% (oral, first-pass metabolism).
Oral bioavailability: levonorgestrel ~100% (nearly complete); ethinyl estradiol ~45-50% (first-pass hepatic metabolism).
No dose adjustment required for mild to moderate renal impairment (GFR >=30 m L/min). Not recommended for use in severe renal impairment (GFR <30 m L/min) due to potential for hormonal disturbances and 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 acute liver disease, active hepatitis, or severe cirrhosis (Child-Pugh class C). For mild (Child-Pugh A) or moderate (Child-Pugh B) impairment, use is not recommended due to potential for altered metabolism; alternative contraception advised.
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 postmenarchal pediatric patients; safety and efficacy established for contraception in females of reproductive age. For adolescents, standard adult dosing may be used after menarche; individualize based on clinical judgment.
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; estrogen-containing contraceptives are not appropriate for this age group. No specific geriatric dosage adjustments applicable as therapy is not recommended.
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 risk of serious cardiovascular side effects from oral contraceptive use. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use this product.
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 thromboembolic disorders,Cigarette smoking increases cardiovascular risk,Elevated blood pressure,Hepatic neoplasia,Gallbladder disease,Glucose intolerance,Ocular lesions (e.g., retinal thrombosis),Headache/migraine,Menstrual irregularities and breakthrough bleeding
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.
Thrombophlebitis or thromboembolic disorders,History of deep vein thrombosis or pulmonary embolism,Cerebrovascular or coronary artery disease,Known or suspected breast cancer,Carcinoma of the endometrium or other estrogen-dependent neoplasia,Undiagnosed abnormal genital bleeding,Cholestatic jaundice of pregnancy or jaundice with prior pill use,Hepatic adenoma or carcinoma,Known or suspected pregnancy,Hypersensitivity to any component,Smoking and age >35 years (relative contraindication)
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
Grapefruit and grapefruit juice may increase ethinyl estradiol levels and risk of adverse effects. Avoid grapefruit products. No other significant food interactions; however, maintain consistent dietary habits as high-fat meals may delay absorption but not reduce overall bioavailability.
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.
Pregnancy category X. Significant risk of fetal harm in the first trimester (limb defects, cardiac anomalies) and second/third trimesters (genital abnormalities, neurodevelopmental effects). Use contraindicated in pregnancy.
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.
Excreted in breast milk. M/P ratio approximately 0.4. May reduce milk production and affect infant hormonal balance. Use with caution, monitor infant for jaundice and growth.
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.
No dosing adjustments required as drug is contraindicated in pregnancy. No pharmacokinetic data available for dose modification.
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 1/35-28 contains norethindrone 1 mg and ethinyl estradiol 35 mcg. For COCs, consider that CYP3A4 inducers (e.g., rifampin, St. John's wort) may reduce contraceptive efficacy. If a patient misses two or more pills, use backup contraception for 7 days. The 28-day pack includes 21 active pills and 7 placebo pills to maintain the regimen.
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 for 28 days; start the next pack immediately after finishing the current pack.,Do not skip pills; if you miss one, take it as soon as remembered. If you miss two or more, use backup contraception for 7 days.,This drug does not protect against HIV or other sexually transmitted infections.,Common side effects include nausea, headache, breast tenderness, and spotting. Contact your provider if you have severe abdominal pain, chest pain, or leg pain.,Do not smoke; smoking increases the risk of serious cardiovascular side effects, especially in women over 35.
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 1/35-28 vs ALTAVERA, answered by our medical review team.
NORTREL 1/35-28 is a Oral Contraceptive that works by Combination of ethinyl estradiol and norethindrone inhibits gonadotropin secretion via negative feedback on the hypothalamic-pituitary-ovarian axis, suppressing ovulation. Additionally, increases cervical mucus viscosity and alters endometrial receptivity.. 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 1/35-28 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 1/35-28 is: One tablet (norethindrone 1 mg + ethinyl estradiol 35 mcg) orally once daily for 28 days, followed by a 7-day placebo period (if using 28-day pack) or continuous if using 21-day pack with 7-day off. Start on first day of menstrual period.. 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 1/35-28 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 1/35-28 is classified as Category C. Pregnancy category X. Significant risk of fetal harm in the first trimester (limb defects, cardiac anomalies) and second/third trimesters (genital abnormalities, neurodevelopmental. 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.