NORDETTE-21
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORDETTE-21 (NORDETTE-21).
Combination oral contraceptive containing ethinyl estradiol and levonorgestrel. Inhibits ovulation by suppressing gonadotropin release, increases viscosity of cervical mucus to prevent sperm penetration, and alters endometrial lining to reduce implantation likelihood.
| Metabolism | Ethinyl estradiol and levonorgestrel are metabolized primarily by CYP3A4. Ethinyl estradiol undergoes phase II conjugation (glucuronidation/sulfation). Levonorgestrel is reduced and conjugated. |
| Excretion | Renal: ~50% (as glucuronide and sulfate conjugates); Fecal: ~40% (enterohepatic recirculation); Biliary: <10% |
| Half-life | Ethinylestradiol: 13 ± 7 hours (terminal), clinically relevant for once-daily dosing; Levonorgestrel: 24 ± 6 hours (terminal), supporting steady-state after ~5 days |
| Protein binding | Ethinylestradiol: 98% bound to albumin; Levonorgestrel: 50% to SHBG, 50% to albumin |
| Volume of Distribution | Ethinylestradiol: 2.5-10 L/kg (extensive tissue distribution); Levonorgestrel: 1.5-4 L/kg (distributes to breast and uterine tissues) |
| Bioavailability | Oral: Ethinylestradiol 40-60% (first-pass metabolism); Levonorgestrel 90-100% (minimal first-pass) |
| Onset of Action | Oral: 24-48 hours for contraceptive effect (requires 7 consecutive days for reliable ovulation suppression) |
| Duration of Action | Contraceptive effect persists for 7 days after last active pill (placebo interval); meaning for missed pills: ≤7 days |
One tablet (0.15 mg levonorgestrel, 0.03 mg ethinyl estradiol) orally once daily for 21 days, followed by 7 days off.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Insufficient data for severe renal impairment (CrCl <30 mL/min); use is not recommended. |
| Liver impairment | Contraindicated in acute hepatic disease, hepatic adenomas, or severe hepatic impairment (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 available. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, same adult dosing (one tablet daily for 21 days) is used based on chronological age and physical development. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific dose adjustment recommended for elderly patients if renal and hepatic function are normal, but alternative contraception should be considered due to increased risk of thromboembolism. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORDETTE-21 (NORDETTE-21).
| Breastfeeding | Passes into breast milk. M/P ratio not determined. Use not recommended during breastfeeding due to potential estrogenic effects on nursing infant. |
| Teratogenic Risk | Trimester 1: No increased risk of major birth defects. Trimester 2-3: Possible risk of fetal harm (e.g., estrogenic effects on genital development) when used inadvertently. |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular adverse events from combination oral contraceptives. Risk increases with age (especially >35 years) and with heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should use other contraception.
| Serious Effects |
Known or suspected pregnancy; current or history of thromboembolic disorders (e.g., DVT, PE, stroke, MI); current or history of cerebrovascular or coronary artery disease; known or suspected breast carcinoma; active liver disease (e.g., hepatitis, cirrhosis); undiagnosed abnormal uterine bleeding; heavy smoking (>15 cigarettes/day) and age ≥35; hypersensitivity to any component.
| Precautions | Increased risk of thromboembolic disorders (e.g., DVT, PE, stroke, MI). Risk increased with smoking, hypertension, hyperlipidemia, diabetes, obesity, and age >35. Discontinue if jaundice, visual disturbances, or migraine develops. Monitor for hypertension, glucose intolerance, and depression. May affect lipid metabolism. Use with caution in women with a history of depression, migraine, or gallbladder disease. |
Loading safety data…
| Monitor blood pressure, weight gain, signs of thromboembolism. In pregnant patients inadvertently exposed, consider ultrasound for fetal genital development. |
| Fertility Effects | Use provides contraception; after discontinuation, fertility returns promptly with no permanent adverse effects. |