ORTHO-NOVUM 7/7/7-28
Clinical safety rating
cautionComprehensive clinical and safety monograph for ORTHO-NOVUM 7/7/7-28 (ORTHO-NOVUM 7/7/7-28).
Combination of estrogen (ethinyl estradiol) and progestin (norethindrone) inhibits gonadotropin secretion, preventing ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial development, reducing implantation likelihood.
| Metabolism | Ethinyl estradiol and norethindrone undergo hepatic metabolism via CYP3A4 and other CYP450 enzymes. Conjugation and sulfation also occur. |
| Excretion | Ethinyl estradiol (EE) is excreted in urine (40%) and feces (60%) as glucuronide and sulfate conjugates. Norethindrone (NET) is excreted primarily in urine (60-80%) as glucuronide conjugates, with 10% in feces. Biliary excretion contributes minimally. |
| Half-life | EE: terminal half-life 13-27 hours (mean ~17 hours); NET: 7-13 hours (mean ~10 hours). Clinical context: steady state reached after 4-7 days; missed pills may reduce contraceptive efficacy. |
| Protein binding | EE: 98% bound to albumin; induces SHBG synthesis, increasing binding capacity. NET: 61% bound to albumin, 36% bound to SHBG. |
| Volume of Distribution | EE: 2.5-5.0 L/kg (mean 4 L/kg); large Vd due to extensive tissue distribution. NET: 1.5-4.0 L/kg (mean 2.5 L/kg); distributes into breast milk. |
| Bioavailability | EE: 38-48% due to first-pass metabolism (sulfation in gut wall and 2-hydroxylation in liver). NET: 50-77% (mean 64%) with high first-pass metabolism. |
| Onset of Action | Oral: contraceptive effect begins after 7 days of consistent daily dosing; ovulation suppression initiated within first cycle. |
| Duration of Action | Contraceptive protection lasts for the 21-day active pill cycle; 7-day placebo interval allows withdrawal bleeding. Duration of contraceptive effect: daily dosing required; 7-day pill-free interval risks ovulation if cycle is extended. |
| Molecular Weight | 310.4 |
One tablet orally once daily for 28 consecutive days (21 active tablets followed by 7 placebo tablets). Each active tablet contains 0.035 mg ethinyl estradiol and varying progestin doses: 7 tablets of 0.5 mg norethindrone, 7 tablets of 0.75 mg norethindrone, and 7 tablets of 1 mg norethindrone.
| Dosage form | TABLET |
| Renal impairment | No specific dosage adjustments recommended for renal impairment. Use with caution in severe renal impairment due to potential for fluid retention and hypertension. |
| Liver impairment | Contraindicated in acute hepatitis, severe cirrhosis, or liver tumors. For mild hepatic impairment (Child-Pugh A), use with caution; no specific dose adjustment established. Not recommended in moderate to severe impairment (Child-Pugh B or C) due to reduced metabolism of steroid hormones. |
| Pediatric use | Not indicated for premenarchal girls. For postmenarchal adolescents, dosage is the same as adults (one tablet daily) but initiation should be based on clinical judgment and individual risk factors. |
| Geriatric use | Not indicated for postmenopausal women. No specific dosing recommendations; use not appropriate in this age group due to lack of contraceptive need and potential increased risk of vascular events. |
| 1st trimester | Category X: Risk of fetal abnormalities (CV malformations, limb defects) associated with sex hormones. Avoid use during pregnancy. |
| 2nd trimester | Category X: Contraindicated due to potential teratogenicity, though risk is lower after organogenesis. Discontinue if pregnancy occurs. |
| 3rd trimester | Category X: Can cause feminization of male fetus, liver tumors in mother. Contraindicated. |
Clinical note
Comprehensive clinical and safety monograph for ORTHO-NOVUM 7/7/7-28 (ORTHO-NOVUM 7/7/7-28).
| Placental transfer | Yes; hormones cross the placenta and can affect fetal development. |
| Breastfeeding | Excreted in breast milk; may reduce milk production and alter composition. Use alternative contraception. Avoid during breastfeeding. |
| Lactation Rating | L5 (Avoid) |
| Teratogenic Risk | Combined hormonal contraceptives (CHCs) including ORTHO-NOVUM 7/7/7-28 are contraindicated during pregnancy. First trimester exposure: no consistent evidence of major malformations (e.g., VACTERL) from epidemiologic studies, but a small increased risk of cardiovascular defects and limb reduction defects cannot be excluded. Second and third trimester exposure: risk of maternal and fetal adverse outcomes, including fetal growth restriction, preterm delivery, and potential masculinization of female fetuses from progestins. Use is contraindicated once pregnancy is suspected or confirmed. |
| Fetal Monitoring | No specific monitoring is required for contraceptive use. If pregnancy occurs, discontinue use. For inadvertent use during pregnancy, no additional fetal monitoring is indicated beyond routine prenatal care. If used postpartum, monitor infant for jaundice or signs of estrogen effects (rare). |
| Fertility Effects | Contraceptive effect is reversible. After discontinuation, normal ovulation and fertility typically return within 1–3 cycles, although some women may experience a delay. No permanent negative impact on fertility; long-term use does not reduce future pregnancy rates. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use. Risk increases with age and heavy smoking (>15 cigarettes/day). Women over 35 who smoke should not use this product.
| Serious Effects |
Known or suspected pregnancyActive or history of thromboembolic disordersCerebrovascular diseaseHormone-sensitive carcinoma (e.g., breast cancer)Hepatic tumors or active liver diseaseUndiagnosed abnormal genital bleeding
| Precautions | Increased risk of thromboembolic disorders; use caution in patients with cardiovascular risk factors. Monitor blood pressure. Discontinue if jaundice, visual disturbances, or migraine occurs. May affect glucose tolerance. Use with caution in patients with history of depression. |
| Food/Dietary | No specific food restrictions; grapefruit juice may increase ethinyl estradiol levels and should be avoided or minimized. High-fat meals may slightly increase absorption but not clinically significant. |
| Clinical Pearls | Fixed-dose combination of norethindrone and ethinyl estradiol; pill sequence has 7 white (0.5mg norethindrone/35mcg EE), 7 light peach (0.75mg/35mcg), 7 peach (1mg/35mcg), 7 green (placebo). Missed pills increase breakthrough bleeding risk; if one pill missed, take as soon as remembered; if two or more, use backup contraception for 7 days. Consider progestin-only alternatives in patients with migraine with aura, uncontrolled hypertension, or smoking >35. Potential for reduced efficacy with enzyme-inducing antiepileptics (e.g., carbamazepine) and rifampin. Increased VTE risk, especially in first year of use. Estrogen-containing contraceptives can increase hepatic clearance of some drugs. Not suitable for breastfeeding within first 6 weeks postpartum due to estrogen effect on milk supply. |
| Patient Advice | Take one pill daily at the same time; start on first day of menstrual period or first Sunday after period begins (check package instructions). · The pill pack has 3 different colored active pills (white, light peach, peach) with increasing progestin dose, followed by 7 green placebo pills; continue taking daily even during placebo week. · If you miss one active pill, take it as soon as remembered and take next pill at usual time (may take 2 pills in one day). · If two or more active pills are missed, take the last missed pill now, discard others, continue with remaining pills; use backup contraception (e.g., condoms) for next 7 days. · Common side effects: nausea, breast tenderness, spotting (especially in first few months); report leg swelling, chest pain, severe headache, or vision changes. · Avoid grapefruit juice as it may increase estrogen levels; no known food restrictions otherwise. · Smoking increases risk of serious cardiovascular events; advise smoking cessation. · Do not use while pregnant; if pregnancy suspected, discontinue and consult healthcare provider. |
Loading safety data…