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Registry Hub
Peer-Reviewed Evidence
HomeDrug RegistryCompareORTHO NOVUM 1 80 28 vs ORTHO NOVUM 1 35 21
Comparative Pharmacology

ORTHO NOVUM 1 80 28 vs ORTHO NOVUM 1 35 21 Comparison

Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.

Clinical EssentialsPharmacokineticsSpecial PopulationsSafety & MonitoringPregnancy & LactationClinical Insights
Differential Analysis

ORTHO-NOVUM 1/80 28 vs ORTHO-NOVUM 1/35-21

Head-to-head clinical comparison of therapeutic indices and safety profiles.

View ORTHO-NOVUM 1/80 28 Monograph View ORTHO-NOVUM 1/35-21 Monograph
ORTHO-NOVUM 1/80 28
Hormonal Contraceptive
Category C
ORTHO-NOVUM 1/35-21
Hormonal Contraceptive
Category C

Clinical Essentials

ORTHO-NOVUM 1/80 28
ORTHO-NOVUM 1/35-21
Mechanism of Action
ORTHO-NOVUM 1/80 28

Combination estrogen-progestin contraceptive; primarily inhibits ovulation by suppressing gonadotropin release (FSH and LH). Also increases cervical mucus viscosity and alters endometrial receptivity.

ORTHO-NOVUM 1/35-21

Combination estrogen-progestin contraceptive; suppresses gonadotropin (FSH and LH) secretion via negative feedback, inhibiting ovulation. Increases cervical mucus viscosity and alters endometrial lining, impairing sperm penetration and implantation.

Indications
ORTHO-NOVUM 1/80 28

Prevention of pregnancy

ORTHO-NOVUM 1/35-21

Prevention of pregnancy,Oral contraception

Standard Dosing
ORTHO-NOVUM 1/80 28

One tablet orally once daily at the same time each day for 28 days (21 active tablets containing norethindrone 1 mg and ethinyl estradiol 80 mcg, followed by 7 placebo tablets).

ORTHO-NOVUM 1/35-21

One tablet orally once daily for 21 days, followed by 7 placebo tablets. Each tablet contains 1 mg norethindrone and 0.035 mg ethinyl estradiol.

Direct Interaction
ORTHO-NOVUM 1/80 28
No Direct Interaction
ORTHO-NOVUM 1/35-21
No Direct Interaction

Pharmacokinetics

ORTHO-NOVUM 1/80 28
ORTHO-NOVUM 1/35-21
Half-Life
ORTHO-NOVUM 1/80 28

Norethindrone: 7-8 hours; mestranol: 10-13 hours (terminal). Steady-state achieved in 5-7 days.

ORTHO-NOVUM 1/35-21

Norethindrone: 7-9 hours (terminal); Ethinyl estradiol: 13-27 hours (terminal). At steady state, clinical contraceptive efficacy is maintained with daily dosing.

Metabolism
ORTHO-NOVUM 1/80 28

Ethinyl estradiol is metabolized primarily via CYP3A4 and undergoes glucuronidation; norethindrone is metabolized via reduction and conjugation.

Special Populations

ORTHO-NOVUM 1/80 28
ORTHO-NOVUM 1/35-21
Renal Adjustments
ORTHO-NOVUM 1/80 28

No specific dose adjustment recommended; use with caution in patients with renal impairment due to potential fluid retention. GFR-based modifications not established.

ORTHO-NOVUM 1/35-21

No dose adjustment required for mild to moderate renal impairment. Insufficient data for severe renal impairment (GFR <30 m L/min/1.73 m²); use caution and monitor for adverse effects.

Hepatic Adjustments
ORTHO-NOVUM 1/80 28

Safety & Monitoring

ORTHO-NOVUM 1/80 28
ORTHO-NOVUM 1/35-21
Black Box Warnings
ORTHO-NOVUM 1/80 28
FDA Black Box Warning

Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age and smoking intensity, especially in women over 35 years of age. Women using oral contraceptives should be strongly advised not to smoke.

Pregnancy & Lactation

ORTHO-NOVUM 1/80 28
ORTHO-NOVUM 1/35-21
Teratogenic Risk
ORTHO-NOVUM 1/80 28

First trimester: No consistent evidence of major malformations, but oral contraceptives are not recommended due to potential risk. Second/third trimester: No specific fetal risks; exposure is not advised due to hormonal effects.

ORTHO-NOVUM 1/35-21

FDA Pregnancy Category X; contraindicated in pregnancy. First trimester: increased risk of neural tube defects, cardiovascular anomalies, and limb reduction defects due to progestin component. Second/third trimesters: feminization of male fetus, potential for congenital anomalies, and possible long-term reproductive effects. No safe use in pregnancy.

Clinical Insights

ORTHO-NOVUM 1/80 28
ORTHO-NOVUM 1/35-21
Clinical Pearls
ORTHO-NOVUM 1/80 28

1. If a dose is missed, take it as soon as remembered; if more than 24 hours late, use backup contraception for 7 days. 2. Monitor blood pressure within 3 months of initiation due to potential hypertensive effects. 3. Caution in patients with migraine with aura due to increased stroke risk. 4. The estrogen component (mestranol) is a prodrug of ethinyl estradiol; bioavailability considerations influence dosing. 5. 21 active pills followed by 7 placebo pills; ensure patient understands the tricycle regimen.

ORTHO-NOVUM 1/35-21

Contains 1 mg norethindrone and 0.035 mg ethinyl estradiol. Monophasic combination oral contraceptive. Risk of venous thromboembolism is dose-dependent; use lowest effective estrogen dose. CYP3A4 inducers (e.g., rifampin, anticonvulsants) may reduce efficacy. Prescribe for cycle control and contraception. Monitor blood pressure at baseline and follow-up. Avoid in smokers over 35 and those with migraine with aura.

Safety Verification

Known Interactions

ORTHO-NOVUM 1/80 28 Risks

No interactions on record

ORTHO-NOVUM 1/35-21 Risks

No interactions on record

Clinical Q&A

Frequently Asked Questions

1. What is the primary difference between ORTHO-NOVUM 1/80 28 and ORTHO-NOVUM 1/35-21?

ORTHO-NOVUM 1/80 28 and ORTHO-NOVUM 1/35-21 are distinct pharmacological agents. ORTHO-NOVUM 1/80 28 belongs to the Hormonal Contraceptive class and is primarily used for Prevention of pregnancy. ORTHO-NOVUM 1/35-21 belongs to the Hormonal Contraceptive class and is primarily used for Prevention of pregnancyOral contraception. Their specific mechanisms of action, pharmacokinetic characteristics, and side effects differ.

2. Are ORTHO-NOVUM 1/80 28 and ORTHO-NOVUM 1/35-21 safe during pregnancy?

The maternal-fetal safety profiles of these drugs differ. ORTHO-NOVUM 1/80 28 carries a safety status of Category C, whereas ORTHO-NOVUM 1/35-21 safety is classified as Category C. Consult a board-certified physician or healthcare specialist to establish an accurate, individualized pregnancy risk assessment before starting either therapy.

ORTHO-NOVUM 1/35-21

Norethindrone: primarily hepatic metabolism via reduction and sulfation, with CYP3A4 involvement. Ethinyl estradiol: hepatic metabolism via CYP3A4, also undergoes conjugation (glucuronidation and sulfation). Undergoes enterohepatic recirculation.

Excretion
ORTHO-NOVUM 1/80 28

Norethindrone: 50-60% renal, 20-30% fecal; mestranol: 30-40% renal, 60-70% fecal.

ORTHO-NOVUM 1/35-21

Renal (approx. 40% as metabolites, <10% unchanged), fecal (approx. 60% as metabolites, primarily via bile).

Protein Binding
ORTHO-NOVUM 1/80 28

Norethindrone: 60-80% bound to albumin and SHBG; mestranol: 90-95% bound to albumin and SHBG.

ORTHO-NOVUM 1/35-21

Norethindrone: 61-77% bound, primarily to SHBG and albumin; Ethinyl estradiol: 97-98% bound, primarily to albumin.

VD (L/kg)
ORTHO-NOVUM 1/80 28

Norethindrone: 2-4 L/kg; mestranol: 1-3 L/kg. Indicates extensive tissue distribution.

ORTHO-NOVUM 1/35-21

Norethindrone: 4-5 L/kg; Ethinyl estradiol: 2-5 L/kg. Indicates extensive tissue distribution exceeding total body water.

Bioavailability
ORTHO-NOVUM 1/80 28

Oral: norethindrone 50-65%, mestranol 40-60% due to first-pass metabolism.

ORTHO-NOVUM 1/35-21

Oral: Norethindrone 50-70%; Ethinyl estradiol 40-50% due to first-pass metabolism.

Contraindicated in patients with Child-Pugh class C cirrhosis. Use with caution in Child-Pugh class A or B; consider alternative contraception due to risk of decreased hormone clearance.

ORTHO-NOVUM 1/35-21

Contraindicated in severe hepatic disease (Child-Pugh class C). For moderate impairment (Child-Pugh class B), avoid use as oral contraceptives may exacerbate liver dysfunction. Mild impairment (Child-Pugh class A): use with caution and monitor liver function.

Pediatric Dosing
ORTHO-NOVUM 1/80 28

Not indicated for premenarchal girls. For postmenarchal adolescents, same dosing as adults: one tablet orally once daily for 28 days.

ORTHO-NOVUM 1/35-21

Safety and efficacy not established in premenarchal girls. Dosing for adolescents post-menarche is same as adults; use with caution and monitor for thromboembolic risk.

Geriatric Dosing
ORTHO-NOVUM 1/80 28

Not indicated for use in postmenopausal women. No geriatric dosing established; use not recommended in women over 50 years due to increased risk of thromboembolism and lack of efficacy for contraception.

ORTHO-NOVUM 1/35-21

Not indicated for postmenopausal women due to absence of ovulation. In perimenopausal women, use lowest effective dose; monitor cardiovascular risk and bone density.

ORTHO-NOVUM 1/35-21
FDA Black Box Warning

Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use (e.g., myocardial infarction, thromboembolism, stroke). Risk increases with age (>35 years) and number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to smoke.

Warnings/Precautions
ORTHO-NOVUM 1/80 28
  • Increased risk of thromboembolic disorders
  • Cerebrovascular disease
  • Myocardial infarction
  • Breast cancer risk
  • Hepatic neoplasia
  • Elevated blood pressure
  • Gallbladder disease
  • Glucose intolerance
  • Ocular lesions
  • Headache
  • Menstrual irregularities
  • Depression
  • Contact lens intolerance
  • Fluid retention
  • Lipid effects
ORTHO-NOVUM 1/35-21

Increased risk of thromboembolic disorders (venous and arterial), stroke, myocardial infarction; hepatic neoplasia; gallbladder disease; hypertension; carbohydrate/lipid effects; ocular lesions (retinal thrombosis); headache/migraine; breakthrough bleeding/spotting; depression; fluid retention; hereditary angioedema; chloasma; liver function impairment.

Contraindications
ORTHO-NOVUM 1/80 28
  • Known or suspected pregnancy
  • Current or past thrombophlebitis or thromboembolic disorders
  • Cerebrovascular or coronary artery disease
  • Known or suspected breast carcinoma
  • Known or suspected 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 hypersensitivity to any component
ORTHO-NOVUM 1/35-21

Thrombophlebitis or thromboembolic disorders; cerebral vascular or coronary artery disease; known or suspected pregnancy; undiagnosed abnormal genital bleeding; known/suspected breast cancer; estrogen-dependent neoplasia; benign/malignant liver tumor (active); known or suspected pregnancy; hypersensitivity to any component; smoking in women >35 years; uncontrolled hypertension; diabetes with vascular disease; migraines with focal aura; major surgery with prolonged immobilization.

Adverse Reactions
ORTHO-NOVUM 1/80 28
Data Pending
ORTHO-NOVUM 1/35-21
Data Pending
Food Interactions
ORTHO-NOVUM 1/80 28

No significant food interactions; however, high-fat meals may delay absorption. Avoid grapefruit juice as it may increase estrogen levels via CYP3A4 inhibition.

ORTHO-NOVUM 1/35-21

Grapefruit and grapefruit juice may increase estrogen levels; avoid excessive consumption. No specific food restrictions; maintain consistent dietary habits to avoid fluctuations in absorption.

Lactation Summary
ORTHO-NOVUM 1/80 28

Excreted in breast milk; may reduce milk production and affect infant. M/P ratio not well established. Avoid use during breastfeeding.

ORTHO-NOVUM 1/35-21

Excreted in breast milk; may reduce milk production and quality. M/P ratio not established for this combination; progestin-only contraceptives preferred. Use only if benefits outweigh risks; monitor infant for jaundice or growth delay.

Pregnancy Dosing
ORTHO-NOVUM 1/80 28

No dose adjustment applicable; drug is contraindicated in pregnancy. Pharmacokinetic changes in pregnancy may alter efficacy but no standard dose modification exists.

ORTHO-NOVUM 1/35-21

Discontinue immediately if pregnancy suspected or confirmed. No dose adjustment is recommended as drug is contraindicated. Pharmacokinetic changes in pregnancy (increased clearance) are not applicable for a contraindicated drug.

Maternal Safety Status
ORTHO-NOVUM 1/80 28
Category C
ORTHO-NOVUM 1/35-21
Category C
Patient Counseling
ORTHO-NOVUM 1/80 28

Take one pill at the same time daily, preferably after dinner to reduce nausea.,If you miss a pill, consult the package insert for instructions; use backup contraception as needed.,Report unusual symptoms: leg pain/swelling (DVT), chest pain/shortness of breath (pulmonary embolism), severe headache, vision changes.,This does not protect against STIs; use condoms for additional protection.,Expect breakthrough bleeding or spotting in the first few months; persistent bleeding requires evaluation.,Smoking increases risk of serious cardiovascular side effects, especially in women over 35.

ORTHO-NOVUM 1/35-21

Take one pill daily at the same time for 21 days, then none for 7 days.,Use backup contraception (e.g., condoms) if you miss a pill or start late.,Common side effects include nausea, breast tenderness, and breakthrough bleeding.,Seek emergency care for severe leg pain, chest pain, sudden severe headache, or vision changes.,Do not smoke while taking this medication, especially if over 35.,Notify your doctor if you develop jaundice, depression, or unexplained weight gain.,This medication does not protect against HIV or other sexually transmitted infections.