N.E.E. 1/35 28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for N.E.E. 1/35 28 (N.E.E. 1/35 28).
Combination oral contraceptive; ethinyl estradiol and norethindrone suppress gonadotropin (FSH and LH) release, preventing ovulation. Also cause cervical mucus thickening and endometrial changes.
| Metabolism | Ethinyl estradiol: primarily metabolized by CYP3A4; undergoes sulfation and glucuronidation. Norethindrone: metabolized in the liver via reduction and glucuronidation. |
| Excretion | Renal: ~50-60% (metabolites, primarily glucuronide conjugates); Fecal: ~30-40% (biliary excretion of metabolites); Unchanged drug: <5% |
| Half-life | Ethinyl estradiol: ~15-19 hours (linear pharmacokinetics); Norethindrone: ~7-9 hours (terminal half-life; steady-state achieved within 5-7 days) |
| Protein binding | Ethinyl estradiol: ~97-98% bound primarily to albumin; Norethindrone: ~96-97% bound to albumin and SHBG |
| Volume of Distribution | Ethinyl estradiol: ~2.5-4 L/kg; Norethindrone: ~3.5-5 L/kg; reflects extensive tissue distribution |
| Bioavailability | Oral: Ethinyl estradiol ~40-50% (first-pass metabolism); Norethindrone ~65-70% (first-pass metabolism) |
| Onset of Action | Oral: Contraceptive effect requires 7 days of continuous dosing to achieve full suppression of ovulation; some immediate effects on cervical mucus within 24-48 hours |
| Duration of Action | Contraceptive coverage persists for the duration of daily dosing; after discontinuation, ovulation may return within 1-2 weeks (variable per individual) |
One tablet orally once daily for 28 days; each tablet contains norethindrone 1 mg and ethinyl estradiol 35 mcg.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended; use with caution in patients with renal impairment. |
| Liver impairment | Contraindicated in patients with acute hepatitis, severe cirrhosis, or liver tumors (benign or malignant). For Child-Pugh Class C: contraindicated. For Child-Pugh Class A or B: use with caution and monitor liver function. |
| Pediatric use | Postmenarchal adolescents: same as adult dosing (one tablet orally once daily). Safety and efficacy established for use after menarche. |
| Geriatric use | Not indicated for postmenopausal women due to lack of need for contraception and potential 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 N.E.E. 1/35 28 (N.E.E. 1/35 28).
| Breastfeeding | Excreted in breast milk in small amounts (estrogen: M/P ratio ~0.5; progestin data limited). May reduce milk production and quality. Not recommended for nursing mothers. Alternative contraception advised. |
| Teratogenic Risk | First trimester: No increased risk of major birth defects from combined oral contraceptives based on population data; however, inadvertent use is not recommended. Second/third trimester: Avoid use due to potential adverse fetal effects including hormonal disruption. Category X for pregnancy contraindication. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age (>35 years) and heavy smoking (>15 cigarettes/day). 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","Pregnancy","Hepatic adenoma or carcinoma","Active liver disease or impaired liver function","Known hypersensitivity to any component","Smoking if age >35 years"]
| Precautions | ["Thrombotic disorders (venous thromboembolism, stroke, MI)","Hepatic neoplasia","Gallbladder disease","Hypertension","Carbohydrate/lipid effects","Ocular lesions (retinal thrombosis)","Carcinoma (breast, cervical)","Hereditary angioedema","Chloasma","Pregnancy (discontinue if pregnant)","Lactation (may reduce milk production)"] |
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| Fetal Monitoring |
| Monitor for signs of thromboembolism, hypertension, and hepatic dysfunction. In pregnant patients (if exposed), assess fetal growth and development via ultrasound if prolonged use occurs. |
| Fertility Effects | Reversible suppression of ovulation. Fertility returns to baseline within 1-3 months after discontinuation. No long-term impairment. |