Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
LO/OVRAL-28 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 of norgestrel, a progestin, and ethinyl estradiol, an estrogen; suppresses gonadotropin secretion (FSH and LH) primarily via progestational activity, inhibiting ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial development, reducing implantation likelihood.
Combination estrogen-progestin contraceptive; suppresses gonadotropin release, inhibiting ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial receptivity.
Prevention of pregnancy,Oral contraceptive
Prevention of pregnancy
One tablet orally once daily for 28 days. Each tablet contains 0.3 mg norgestrel and 0.03 mg ethinyl estradiol. Active tablets (21 days) followed by placebo tablets (7 days).
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: 20-40 hours; Ethinyl estradiol: 13-27 hours. Steady-state achieved after 3-5 half-lives.
Ethinyl estradiol: 17.4 ± 5.6 h (terminal); norethindrone: 10.9 ± 1.6 h (terminal); clinically, steady-state achieved within 5-7 days.
Hepatic via CYP3A4 for ethinyl estradiol; norgestrel metabolized via reduction and conjugation.
Ethinylestradiol undergoes hepatic metabolism via CYP3A4; norethindrone undergoes reduction and conjugation in the liver.
Renal (approx. 50% as metabolites, <1% unchanged); biliary/fecal (approx. 50% as metabolites).
Renal 50% (metabolites), fecal 50% (biliary elimination of conjugates).
Norgestrel: 93-99% (primarily SHBG and albumin); Ethinyl estradiol: 97-98% (primarily albumin and SHBG).
Ethinyl estradiol: 97-98% bound to albumin; norethindrone: 93% bound to albumin and SHBG.
Norgestrel: 3.0 L/kg; Ethinyl estradiol: 4.0 L/kg.
Ethinyl estradiol: 2.3-4.3 L/kg; norethindrone: 4.4 L/kg; indicates extensive tissue distribution.
Oral: Norgestrel 85-90%; Ethinyl estradiol 38-48% due to first-pass metabolism.
Ethinyl estradiol: 40-45% (oral; first-pass metabolism); norethindrone: 64-67% (oral).
No dosage adjustment required for renal impairment. However, use with caution in patients with renal dysfunction due to potential fluid retention.
No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment or acute renal failure.
Contraindicated in patients with Child-Pugh Class B or C cirrhosis. For Child-Pugh Class A, use with caution; limited data, but no specific dose adjustment recommended.
Contraindicated in acute or chronic hepatic dysfunction, including Child-Pugh class A, B, or C. Avoid use if liver function tests are abnormal.
Not indicated for use before menarche. For post-menarchal adolescents, the same dosing as adults: one tablet orally daily for 28-day cycles.
Not indicated for use before menarche. For postmenarchal adolescents, use same dosing as adults (one tablet orally once daily).
Not indicated in postmenopausal women. No geriatric-specific dosing; not for use in elderly due to lack of need for contraception after menopause.
Not indicated for use in postmenopausal women.
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use. Risk increases with age and smoking intensity (especially in women over 35). 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.
Thrombotic disorders (e.g., venous thromboembolism, stroke, myocardial infarction); hepatic neoplasia; hypertension; gallbladder disease; carbohydrate/lipid effects; ocular lesions; breakthrough bleeding; missed periods; ectopic pregnancy risk; lactation; depression.
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; history of deep vein thrombosis or pulmonary embolism; cerebrovascular or coronary artery disease; known or suspected breast carcinoma; endometrial carcinoma 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.
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 does not notably affect ethinyl estradiol levels, but consistent intake is recommended to maintain uniform hormone levels. Avoid excessive alcohol consumption as it may impair liver function and alter hormone metabolism.
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 known association with major congenital anomalies, but small increased risk of cardiovascular defects and limb reduction defects reported in some studies. Second/third trimesters: Use not recommended due to potential adverse effects on fetal development including virilization of female fetus and hepatic adenoma; contraindicated in known pregnancy.
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.
Enters breast milk in small amounts; estrogen and progestin may reduce milk production and composition. M/P ratio not established. Generally avoided during breastfeeding due to theoretical risks; low-dose progestin-only contraception preferred.
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.
Contraindicated in pregnancy; no dose adjustments applicable as use is not recommended. Pharmacokinetic changes in pregnancy include increased clearance of ethinyl estradiol and norgestrel, but pregnancy contraindication precludes dose modification.
Contraindicated in pregnancy; no dose adjustment applicable. If inadvertently used, discontinue immediately.
LO/OVRAL-28 is a combination oral contraceptive containing norgestrel and ethinyl estradiol. It is indicated for pregnancy prevention. The 28-day regimen includes 21 active pills and 7 placebo pills. Counsel patients to take at the same time daily. Breakthrough bleeding is common in the first few cycles. If a dose is missed, follow the specific package instructions. Anti-infectives like rifampin may reduce efficacy; additional contraception is recommended.
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 pill daily at the same time each day.,If you miss a pill, refer to the package insert for instructions; use backup contraception if needed.,Common side effects include nausea, breast tenderness, and spotting, which usually improve after a few cycles.,Smoking increases risk of serious cardiovascular side effects; do not smoke while taking this medication.,Inform your healthcare provider if you have a history of blood clots, migraines with aura, or liver disease.
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-28 vs DEMULEN 1/35-28, answered by our medical review team.
LO/OVRAL-28 is a Combination Oral Contraceptive that works by Combination of norgestrel, a progestin, and ethinyl estradiol, an estrogen; suppresses gonadotropin secretion (FSH and LH) primarily via progestational activity, inhibiting ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial development, reducing implantation likelihood.. 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-28 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-28 is: One tablet orally once daily for 28 days. Each tablet contains 0.3 mg norgestrel and 0.03 mg ethinyl estradiol. Active tablets (21 days) followed by placebo tablets (7 days).. 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-28 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-28 is classified as Category C. First trimester: No known association with major congenital anomalies, but small increased risk of cardiovascular defects and limb reduction defects reported in some studies. Secon. 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.