NORLESTRIN 28 1/50
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORLESTRIN 28 1/50 (NORLESTRIN 28 1/50).
Combination estrogen-progestin oral contraceptive; suppresses gonadotropin release via negative feedback on pituitary, inhibits ovulation, thickens cervical mucus, alters endometrial receptivity.
| Metabolism | Ethinyl estradiol: primarily metabolized by CYP3A4 via hydroxylation, conjugated as glucuronides and sulfates. Norethindrone: reduced to dihydro- and tetrahydro-metabolites, conjugated, with minor CYP3A4 involvement. |
| Excretion | Norethindrone: 40% renal, 60% fecal; ethinyl estradiol: 40% renal, 60% fecal. |
| Half-life | Norethindrone: 8 hours; ethinyl estradiol: 12-15 hours; steady state achieved within 5-10 days. |
| Protein binding | Norethindrone: 80% bound to albumin and SHBG; ethinyl estradiol: 97% bound to albumin. |
| Volume of Distribution | Norethindrone: 2.5 L/kg; ethinyl estradiol: 4.5 L/kg; indicates extensive distribution into tissues. |
| Bioavailability | Norethindrone: 100% oral; ethinyl estradiol: 45% oral due to first-pass metabolism. |
| Onset of Action | Oral: 24 hours for ovarian suppression; 7 days for full contraceptive effect. |
| Duration of Action | 24 hours; missed pill instructions recommend backup contraception if >24 hours late. |
One tablet orally once daily, each containing norethindrone 1 mg and ethinyl estradiol 50 mcg.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment or renal failure. |
| Liver impairment | Contraindicated in Child-Pugh class B and C (moderate to severe hepatic impairment). Use with caution in Child-Pugh class A; monitor liver function. |
| Pediatric use | Not indicated for premenarchal females. For postmenarchal adolescents, same as adult dosing: one tablet orally once daily. |
| Geriatric use | Not indicated for postmenopausal women. No specific geriatric dose adjustments; consider increased risk of thromboembolism and cardiovascular disease in older women. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORLESTRIN 28 1/50 (NORLESTRIN 28 1/50).
| Breastfeeding | Excreted in breast milk in small amounts (progestin: M/P ratio ~0.5; estrogen: minimal). May reduce milk production and affect infant development. Use during lactation is generally not recommended; alternative contraception should be considered. |
| Teratogenic Risk | FDA Pregnancy Category X. Contraindicated in pregnancy due to known teratogenicity. First trimester: Increased risk of neural tube defects, congenital heart defects, and limb reduction defects. Second and third trimesters: Associated with fetal adrenal suppression, masculinization of female fetuses (due to progestin component), and potential for other adverse outcomes. Exposure during pregnancy warrants immediate discontinuation. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Women over 35 who smoke should not use this product.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders, cerebrovascular or coronary artery disease, known or suspected breast carcinoma, endometrial carcinoma or other estrogen-dependent neoplasia, undiagnosed abnormal genital bleeding, known or suspected pregnancy, jaundice with prior pill use, hepatic adenoma or carcinoma.
| Precautions | Thrombotic disorders (DVT, PE, stroke, MI), hypertension, gallbladder disease, impaired liver function, hypertriglyceridemia, glucose intolerance, depression, fluid retention, irregular bleeding, ectopic pregnancy risk. |
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| Fetal Monitoring | Not applicable for continued use in pregnancy (contraindicated). If accidental exposure occurs, monitor for fetal anomalies via ultrasound, consider amniocentesis for chromosomal analysis if indicated, and assess for potential estrogenic effects. In non-pregnant patients on therapy, routine blood pressure, breast exams, and liver function tests are recommended. |
| Fertility Effects | Suppresses ovulation via hormonal mechanisms. Fertility typically returns rapidly upon discontinuation. No evidence of permanent negative effects on fertility. May cause menstrual irregularities initially upon cessation. |