NORLESTRIN 28 1/50
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 340.5 |
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 | Contraindicated in pregnancy. Use in first trimester may cause fetal harm due to hormonal effects. Not indicated for use during pregnancy. |
| 2nd trimester | Contraindicated. Avoid use in second trimester. Risk of adverse fetal outcomes including congenital anomalies. |
| 3rd trimester | Contraindicated. Use in third trimester associated with potential fetal and neonatal adverse effects, including virilization of female fetus and hormonal disturbances. |
Clinical note
Comprehensive clinical and safety monograph for NORLESTRIN 28 1/50 (NORLESTRIN 28 1/50).
| Placental transfer | Estrogens and progestins cross the placenta. Degree of transfer is significant, with fetal serum levels reaching up to 10-20% of maternal levels. |
| Breastfeeding | Small amounts of estrogens and progestins are excreted in breast milk. May reduce milk production and quality. Use only if clearly needed, with caution, and monitor infant for adverse effects. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ 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 |
PregnancyKnown or suspected breast cancerEstrogen-dependent neoplasiaActive thrombophlebitis or thromboembolic disordersHistory of deep vein thrombosis or pulmonary embolismCerebrovascular diseaseSignificant liver disease or impairmentUndiagnosed abnormal genital bleedingKnown hypersensitivity to any component
| Precautions | Thrombotic disorders (DVT, PE, stroke, MI), hypertension, gallbladder disease, impaired liver function, hypertriglyceridemia, glucose intolerance, depression, fluid retention, irregular bleeding, ectopic pregnancy risk. |
| Food/Dietary | No clinically significant food interactions. Grapefruit juice may moderately increase ethinyl estradiol levels; avoid large amounts. Report any known food allergies to excipients. |
| Clinical Pearls | Norlestrin 28 1/50 (norethindrone 1 mg + ethinyl estradiol 50 mcg) is a high-estrogen-dose combination oral contraceptive. Use for cycle control or contraception; 50 mcg EE raises thromboembolic risk, contraindicated in smokers >35 years, hypertension, migraine with aura, or BMI >30 kg/m². Advise consistent daily timing; missed pills increase breakthrough bleeding and contraceptive failure. |
| Patient Advice | Take one tablet daily at the same time, even during placebo week. · Use backup contraception if you miss more than one active pill. · Do not smoke; risk of blood clots increases, especially over age 35. · Common side effects include nausea, headache, and breast tenderness. · Notify your provider about severe leg pain, chest pain, or vision changes. |
Loading safety data…