NORDETTE-28
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORDETTE-28 (NORDETTE-28).
| Breastfeeding | Excreted in human breast milk in small amounts. M/P ratio not established. May reduce milk production and quality. Use during breastfeeding is not recommended; consider alternative contraception or discontinue nursing. |
| 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. |
■ 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 |
["Known or suspected pregnancy","Current or past history of thrombotic disorders (e.g., DVT, PE)","Cerebrovascular or coronary artery disease","Valvular heart disease with complications","Uncontrolled hypertension","Diabetes with vascular involvement","Headaches with focal neurological symptoms (e.g., migraine with aura)","Major surgery with prolonged immobilization","Known or suspected breast cancer or estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Hepatic adenoma or carcinoma, known or suspected","Active liver disease with impaired liver function","Hypersensitivity to any component","Cigarette smoking in women over 35 years old"]
| 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"] |
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| 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. |