Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
LO/OVRAL vs DEMULEN 1/35-28
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Combination estrogen-progestin oral contraceptive; suppresses gonadotropin release, primarily FSH and LH, inhibiting ovulation; increases viscosity of cervical mucus, impeding sperm penetration; alters endometrial receptivity.
Combination estrogen-progestin contraceptive; suppresses gonadotropin release, inhibiting ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial receptivity.
Prevention of pregnancy,Dysfunctional uterine bleeding,Hormonal contraception
Prevention of pregnancy
One tablet (30 mcg ethinyl estradiol, 0.3 mg norgestrel) orally once daily for 28-day cycle (21 active, 7 placebo).
One tablet (contains 1 mg ethynodiol diacetate and 35 mcg ethinyl estradiol) orally once daily at the same time each day for 21 days, followed by 7 days of placebo or no tablets.
Norgestrel (levonorgestrel): 11-45 hours (mean ~24 hours); ethinyl estradiol: 7-21 hours (mean ~14 hours). Half-life increases slightly with repeated dosing due to saturable metabolism.
Ethinyl estradiol: 17.4 ± 5.6 h (terminal); norethindrone: 10.9 ± 1.6 h (terminal); clinically, steady-state achieved within 5-7 days.
Ethinyl estradiol is primarily metabolized by CYP3A4; norgestrel is metabolized via reduction and conjugation; both undergo first-pass metabolism.
Ethinylestradiol undergoes hepatic metabolism via CYP3A4; norethindrone undergoes reduction and conjugation in the liver.
Urine (50-60% as conjugated metabolites), feces (30-40% as metabolites), enterohepatic recirculation present.
Renal 50% (metabolites), fecal 50% (biliary elimination of conjugates).
Levonorgestrel: 97-99% (primarily to sex hormone-binding globulin, SHBG, and albumin); ethinyl estradiol: 97-98% (primarily to albumin, increases SHBG levels).
Ethinyl estradiol: 97-98% bound to albumin; norethindrone: 93% bound to albumin and SHBG.
Levonorgestrel: 1.0-1.3 L/kg; ethinyl estradiol: 2.3-3.0 L/kg. Reflects extensive tissue distribution and binding.
Ethinyl estradiol: 2.3-4.3 L/kg; norethindrone: 4.4 L/kg; indicates extensive tissue distribution.
Oral: levonorgestrel ~100% (first-pass metabolism <10%), ethinyl estradiol 38-48% due to first-pass conjugation in gut wall and liver.
Ethinyl estradiol: 40-45% (oral; first-pass metabolism); norethindrone: 64-67% (oral).
No dosage adjustment required for mild to moderate impairment. Not recommended in severe renal impairment (e GFR <30 m L/min/1.73m²) due to limited data.
No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment or acute renal failure.
Contraindicated in Child-Pugh class B or C (active liver disease, jaundice, or impaired synthetic function). Use discontinued if hepatic function deteriorates.
Contraindicated in acute or chronic hepatic dysfunction, including Child-Pugh class A, B, or C. Avoid use if liver function tests are abnormal.
Post-menarche adolescents: Same dosing as adults (30 mcg ethinyl estradiol/0.3 mg norgestrel daily). Not indicated pre-menarche.
Not indicated for use before menarche. For postmenarchal adolescents, use same dosing as adults (one tablet orally once daily).
Not indicated for postmenopausal women. Higher risk of thromboembolism and cardiovascular events in women >40 years, especially if smoking or other risk factors.
Not indicated for use in postmenopausal women.
Cigarette smoking increases risk of serious cardiovascular events from oral contraceptive use; risk increases with age (especially in women over 35 years) and with heavy smoking (≥15 cigarettes/day); women should be strongly advised not to smoke.
Cigarette smoking increases risk of serious cardiovascular events. Risk increases with age and smoking intensity. Women over 35 who smoke should not use this product.
Increased risk of thromboembolic disorders (e.g., MI, stroke, VTE); hepatic adenoma; risk of breast cancer; hypertension; gallbladder disease; impaired glucose tolerance; cholestatic jaundice; ocular lesions (e.g., retinal thrombosis); use in pregnancy; fluid retention; hereditary angioedema.
Increased risk of thromboembolic disorders,Cerebrovascular disease,Myocardial infarction,Hepatic neoplasia,Gallbladder disease,Hypertension,Carbohydrate/lipid effects,Headache,Uterine bleeding,Ocular lesions,Depression
Thrombophlebitis or thromboembolic disorders; cerebrovascular or coronary artery disease; known or suspected breast carcinoma; estrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; known or suspected pregnancy; hepatic adenoma or malignancy; cholestatic jaundice of pregnancy or jaundice with prior pill use; active liver disease; hypersensitivity to any component; cigarette smoking in women ≥35 years; uncontrolled hypertension; diabetes with vascular involvement; headaches with focal neurological symptoms; major surgery with prolonged immobilization.
Known or suspected pregnancy,Current or past thrombosis,Cerebrovascular or coronary artery disease,Valvular heart disease with complications,Severe hypertension,Diabetes with vascular involvement,Headaches with focal neurological symptoms,Major surgery with prolonged immobilization,Known or suspected breast cancer,Endometrial cancer or other estrogen-dependent neoplasia,Undiagnosed abnormal genital bleeding,Cholestatic jaundice of pregnancy or jaundice with prior pill use,Hepatic adenomas or carcinomas,Active liver disease,Known hypersensitivity to any component
No significant food interactions. Grapefruit juice may increase ethinyl estradiol levels via CYP3A4 inhibition, but clinical relevance is minimal with low-dose pills. Avoid using St. John's wort, which may decrease contraceptive efficacy.
No significant food interactions. Grapefruit juice has minimal effect on ethinyl estradiol; no restriction needed. Avoid excessive alcohol, which may impair adherence or increase liver enzymes. St. John's wort reduces contraceptive efficacy and should be avoided.
First trimester: No increased risk of major malformations based on epidemiological studies. Second/third trimesters: Exposure may increase risk of fetal liver tumors (rare) and possibly cardiovascular malformations; contraindicated due to feminization of male fetus. Post-market reports: Possible association with neonatal jaundice, cholestasis, and transient hormonal effects.
First trimester: Increased risk of neural tube defects, cardiovascular anomalies, and oral clefts (OR ~1.3-1.6). Second/third trimester: Androgenization of female fetus (clitoromegaly, labial fusion) due to progestin component; possible association with hypospadias in males with first-trimester exposure. Avoid use in pregnancy.
Contraindicated during breastfeeding due to potential adverse effects on milk production and infant hormonal balance. M/P ratio not established; ethinyl estradiol and norgestrel are excreted into human milk in small amounts but insufficient data on infant exposure.
Excreted in breast milk; estimated infant dose <1% of maternal dose. M/P ratio not available for ethinyl estradiol/ethynodiol diacetate. May reduce milk production and quality. Use only if benefits outweigh risks; lowest effective dose recommended.
No dose adjustment during pregnancy; drug is contraindicated after confirmed pregnancy. Pregnancy-induced changes in pharmacokinetics (increased clearance, volume of distribution) may reduce efficacy, but use is not recommended.
Contraindicated in pregnancy; no dose adjustment applicable. If inadvertently used, discontinue immediately.
Lo/Ovral is a low-dose combined oral contraceptive containing ethinyl estradiol and norgestrel. Not recommended for use in women with BMI > 35 kg/m² due to increased thromboembolic risk. Advise consistent daily timing within a 3-hour window to maintain efficacy. Missed pill management: if one pill is missed >12 hours late, take missed pill and continue with next pill at normal time; if two or more pills are missed, take the most recent missed pill and use backup contraception for 7 days. Consider CYP3A4 inducers (e.g., rifampin, St. John's wort) that may reduce efficacy.
DEMULEN 1/35-28 (ethinyl estradiol 35 mcg + ethynodiol diacetate 1 mg) is a monophasic combined oral contraceptive. Its progestin has mild androgenic activity, which may be less favorable for acne-prone patients compared to third-generation pills. The 28-day pack includes 21 active pills and 7 inert pills. Counsel patients to take at the same time daily; missed pills increase breakthrough bleeding and pregnancy risk. It may be used off-label for cycle control in patients without contraindications.
Take one tablet daily at the same time every day.,Do not skip pills; if you miss a pill, follow the missed pill instructions in the package insert.,Use backup contraception (e.g., condoms) if you vomit or have severe diarrhea within 4 hours of taking a pill.,Avoid smoking, especially if over 35 years old, as it increases risk of serious cardiovascular side effects.,Tell your healthcare provider about all medications and supplements you take, as some may interfere with birth control effectiveness.,Lo/Ovral does not protect against HIV or other sexually transmitted infections.,Store at room temperature away from moisture and heat.
Take one pill daily at the same time, preferably after dinner to reduce nausea.,If you miss one pill, take it as soon as remembered; if missed more than one, use backup contraception for 7 days.,Smoking increases risk of blood clots; especially dangerous if over 35 and smokes.,Some antibiotics (e.g., rifampin) and antiseizure medications may reduce effectiveness.,Report any signs of blood clot: sudden leg pain/swelling, chest pain, shortness of breath, or sudden severe headache.,Breakthrough bleeding is common in first 3 cycles; if persistent, contact your healthcare provider.,Do not use if pregnant; if pregnancy occurs, stop immediately.
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 LO/OVRAL vs DEMULEN 1/35-28, answered by our medical review team.
LO/OVRAL is a Combination Oral Contraceptive that works by Combination estrogen-progestin oral contraceptive; suppresses gonadotropin release, primarily FSH and LH, inhibiting ovulation; increases viscosity of cervical mucus, impeding sperm penetration; alters endometrial receptivity.. DEMULEN 1/35-28 is a Combination Oral Contraceptive that works by Combination estrogen-progestin contraceptive; suppresses gonadotropin release, inhibiting ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial receptivity.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between LO/OVRAL and DEMULEN 1/35-28 depend on the specific clinical indication. These are both Combination Oral Contraceptive agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of LO/OVRAL is: One tablet (30 mcg ethinyl estradiol, 0.3 mg norgestrel) orally once daily for 28-day cycle (21 active, 7 placebo).. The standard adult dose of DEMULEN 1/35-28 is: One tablet (contains 1 mg ethynodiol diacetate and 35 mcg ethinyl estradiol) orally once daily at the same time each day for 21 days, followed by 7 days of placebo or no tablets.. 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 LO/OVRAL and DEMULEN 1/35-28 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. LO/OVRAL is classified as Category C. First trimester: No increased risk of major malformations based on epidemiological studies. Second/third trimesters: Exposure may increase risk of fetal liver tumors (rare) and pos. DEMULEN 1/35-28 is classified as Category C. First trimester: Increased risk of neural tube defects, cardiovascular anomalies, and oral clefts (OR ~1.3-1.6). Second/third trimester: Androgenization of female fetus (clitoromeg. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.