NORTREL 1/35-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORTREL 1/35-28 (NORTREL 1/35-28).
Combination of ethinyl estradiol and norethindrone inhibits gonadotropin secretion via negative feedback on the hypothalamic-pituitary-ovarian axis, suppressing ovulation. Additionally, increases cervical mucus viscosity and alters endometrial receptivity.
| Metabolism | Primarily hepatic via CYP3A4; ethinyl estradiol undergoes first-pass metabolism; norethindrone is metabolized via reduction and conjugation. |
| Excretion | Renal 60-70% (as glucuronide and sulfate conjugates), fecal 20-30% (via biliary excretion). |
| Half-life | Norethindrone: 5-14 hours (terminal); ethinyl estradiol: 13-27 hours (terminal). Context: steady-state after 5-7 days; dose adjustment in hepatic impairment. |
| Protein binding | Norethindrone: 99% bound (SHBG, albumin); ethinyl estradiol: 98% bound (albumin, SHBG). |
| Volume of Distribution | Norethindrone: 4-5 L/kg (extensive tissue distribution); ethinyl estradiol: 2-4 L/kg (significant tissue uptake). |
| Bioavailability | Norethindrone: 47-73% (oral); ethinyl estradiol: 38-48% (oral, first-pass metabolism). |
| Onset of Action | Oral: 7 days for contraceptive effect (suppression of ovulation); 2-3 hours for peak serum levels. |
| Duration of Action | 24 hours (contraceptive coverage requires daily dosing); sustained effect after 7 days of consecutive therapy. |
One tablet (norethindrone 1 mg + ethinyl estradiol 35 mcg) orally once daily for 28 days, followed by a 7-day placebo period (if using 28-day pack) or continuous if using 21-day pack with 7-day off. Start on first day of menstrual period.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR >=30 mL/min). Not recommended for use in severe renal impairment (GFR <30 mL/min) due to potential for hormonal disturbances and adverse effects. |
| Liver impairment | Contraindicated in acute liver disease, active hepatitis, or severe cirrhosis (Child-Pugh class C). For mild (Child-Pugh A) or moderate (Child-Pugh B) impairment, use is not recommended due to potential for altered metabolism; alternative contraception advised. |
| Pediatric use | Not indicated for use in postmenarchal pediatric patients; safety and efficacy established for contraception in females of reproductive age. For adolescents, standard adult dosing may be used after menarche; individualize based on clinical judgment. |
| Geriatric use | Not indicated for use in postmenopausal women; estrogen-containing contraceptives are not appropriate for this age group. No specific geriatric dosage adjustments applicable as therapy is not recommended. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORTREL 1/35-28 (NORTREL 1/35-28).
| Breastfeeding | Excreted in breast milk. M/P ratio approximately 0.4. May reduce milk production and affect infant hormonal balance. Use with caution, monitor infant for jaundice and growth. |
| Teratogenic Risk | Pregnancy category X. Significant risk of fetal harm in the first trimester (limb defects, cardiac anomalies) and second/third trimesters (genital abnormalities, neurodevelopmental effects). Use contraindicated in pregnancy. |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular side effects from oral contraceptive use. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use this product.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders","History of deep vein thrombosis or pulmonary embolism","Cerebrovascular or coronary artery disease","Known or suspected breast cancer","Carcinoma of the endometrium or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior pill use","Hepatic adenoma or carcinoma","Known or suspected pregnancy","Hypersensitivity to any component","Smoking and age >35 years (relative contraindication)"]
| Precautions | ["Increased risk of thromboembolic disorders","Cigarette smoking increases cardiovascular risk","Elevated blood pressure","Hepatic neoplasia","Gallbladder disease","Glucose intolerance","Ocular lesions (e.g., retinal thrombosis)","Headache/migraine","Menstrual irregularities and breakthrough bleeding"] |
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| Monitor blood pressure, liver function, glucose tolerance, and thyroid function. Fetal ultrasound for anomalies if accidental exposure occurs. |
| Fertility Effects | Suppresses ovulation, may delay return to fertility after discontinuation. No permanent impact on fertility. |