NORDETTE-28
Clinical safety rating
cautionComprehensive clinical and safety monograph for NORDETTE-28 (NORDETTE-28).
Combined estrogen-progestin oral contraceptive. Suppresses gonadotropin (FSH, LH) release from pituitary, inhibiting ovulation. Increases cervical mucus viscosity and alters endometrial lining.
| Metabolism | Ethinylestradiol is metabolized primarily via CYP3A4; levonorgestrel is metabolized via CYP3A4 and to a lesser extent CYP2C19 and CYP2C9. |
| Excretion | Renal: ~50% as metabolites, ~20% unchanged; Fecal: ~30% as metabolites; Biliary: minimal. |
| Half-life | Ethinyl estradiol: 13-27 hours (mean 17 hours); Levonorgestrel: 11-45 hours (mean 24 hours); clinical context: steady-state reached after 5-7 days. |
| Protein binding | Ethinyl estradiol: ~97% bound to albumin; Levonorgestrel: ~98% bound to SHBG (sex hormone-binding globulin) and albumin. |
| Volume of Distribution | Ethinyl estradiol: 2.9-4.3 L/kg; Levonorgestrel: 1.8-2.1 L/kg; clinical meaning: extensive tissue distribution, not limited to plasma. |
| Bioavailability | Oral: Ethinyl estradiol ~45% (first-pass metabolism); Levonorgestrel ~100% (minimal first-pass). |
| Onset of Action | Oral: contraceptive effect requires 7 days of continuous dosing; peak serum levels in 1-2 hours. |
| Duration of Action | Oral: contraceptive protection lasts 24 hours per dose; clinical note: missed dose >12 hours reduces efficacy. |
| Molecular Weight | 359.5 |
One tablet orally once daily for 28 consecutive days.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment or acute renal failure due to potential for fluid retention and hyperkalemia. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use with caution and monitor liver function; no specific dose adjustment recommended. |
| Pediatric use | Not indicated for use in pediatric patients before menarche. For postmenarchal adolescents, same dosing as adults: one tablet orally daily for 28 days. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific dose adjustment in elderly patients without contraindications, but consider increased risk of thromboembolism and cardiovascular events. |
| 1st trimester | Contraindicated due to risk of teratogenicity (oral clefts, cardiac defects) from estrogen exposure. Use only if no other alternative and risk is justified. |
| 2nd trimester | Contraindicated. Estrogen can affect fetal development; progestins may cause ambiguous genitalia in female fetuses. |
| 3rd trimester | Contraindicated. Postnatal effects include withdrawal bleeding, jaundice, and potential estrogenic effects on the fetus. |
Clinical note
Comprehensive clinical and safety monograph for NORDETTE-28 (NORDETTE-28).
| Placental transfer | Ethinyl estradiol and levonorgestrel cross the placenta. Detectable in fetal tissues and cord blood. |
| Breastfeeding | Excreted in breast milk in small amounts. May reduce milk production and composition. Use only if clearly needed and benefits outweigh risks. Progestin-only alternatives preferred. |
| Lactation Rating | L3 - Limited Data (Possibly Hazardous) |
| Teratogenic Risk | FDA Pregnancy Category X. Estrogens and progestins are contraindicated in pregnancy due to risk of fetal harm, including cardiovascular defects and limb reduction defects. Use during first trimester is associated with congenital anomalies; second and third trimester use may cause genitourinary abnormalities and delayed fetal development. |
| Fetal Monitoring | Monitor for signs of pregnancy, as missed doses increase risk. If pregnancy occurs, discontinue immediately. Assess fetal development via ultrasound if inadvertent exposure. Monitor maternal blood pressure and glucose levels due to potential hormonal effects. |
| Fertility Effects | May delay return to fertility after discontinuation. No permanent effects on fertility. Normal ovulation resumes after stopping, typically within few cycles. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combined oral contraceptives. Risk increases with age (especially >35 years) and with heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use this product.
| Serious Effects |
PregnancyThrombophlebitis or thromboembolic disordersCerebrovascular or coronary artery diseaseKnown or suspected breast carcinomaEstrogen-dependent neoplasiaUndiagnosed abnormal genital bleedingBenign or malignant liver tumor (active)Known hypersensitivity to componentsAge >35 years with smoking (15+ cigarettes/day)Severe hypertension (BP ≥160/100 mmHg)Diabetes mellitus with vascular involvementMigraine with focal aura (any age)Major surgery with prolonged immobilization
| Precautions | Risk of thrombotic and thromboembolic events (venous and arterial), Risk of myocardial infarction and stroke, Increased risk of hepatic neoplasia, Elevated blood pressure, Gallbladder disease, Carbohydrate and lipid effects, Exacerbation of hereditary angioedema, Chloasma, Retinal thrombosis, Depression, Reduced efficacy with enzyme-inducing drugs, Irregular bleeding, Amenorrhea and oligomenorrhea, Lactation |
| Food/Dietary | Avoid large amounts of grapefruit or grapefruit juice as they can increase ethinyl estradiol levels. St. John's wort may reduce contraceptive efficacy. No other specific dietary restrictions. A well-balanced diet is recommended. |
| Clinical Pearls | Nordette-28 is a combination oral contraceptive containing ethinyl estradiol and levonorgestrel. In case of missed pills, follow package instructions; if two or more pills are missed, use backup contraception for 7 days. The risk of venous thromboembolism is increased in smokers over age 35; strongly advise smoking cessation. Start the first pill on the first day of menses or first Sunday after onset. Monitor for breakthrough bleeding, especially in the first few cycles. Grapefruit juice may increase ethinyl estradiol levels; avoid large quantities. |
| Patient Advice | Take one pill daily at the same time each day to maintain hormone levels. · If you miss a pill, take it as soon as remembered; if more than 24 hours late, follow package directions and use backup contraception. · Do not smoke while taking this medication, especially if over 35, due to increased risk of blood clots. · Use additional non-hormonal contraception if you vomit or have severe diarrhea within 3-4 hours of taking a pill. · Nordette-28 does not protect against sexually transmitted infections; use condoms for STI prevention. |
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