NYLIA 1/35
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NYLIA 1/35 (NYLIA 1/35).
Combination oral contraceptive consisting of norethindrone (a progestin) and ethinyl estradiol (an estrogen). Inhibits ovulation by suppressing gonadotropin release, increases viscosity of cervical mucus to impede sperm penetration, and alters endometrial lining.
| Metabolism | Ethinyl estradiol is metabolized primarily via CYP3A4; norethindrone is metabolized via reduction and glucuronidation, with some involvement of CYP3A4. |
| Excretion | Renal: 40-60% (as metabolites, mainly ethinyl estradiol glucuronide and sulfate conjugates and norethindrone metabolites). Biliary/fecal: 30-50% (as conjugates and metabolites). |
| Half-life | Norethindrone: 5-14 hours (mean ~8 hours); Ethinyl estradiol: 7-36 hours (mean ~14 hours). Clinically, steady-state is achieved within 5-7 days. |
| Protein binding | Norethindrone: 80-95% (mainly to SHBG and albumin). Ethinyl estradiol: 98-99% (mainly to albumin, induces SHBG synthesis). |
| Volume of Distribution | Norethindrone: ~4 L/kg (large Vd indicates extensive tissue distribution). Ethinyl estradiol: ~3 L/kg (distributes to breast, uterine, and hepatic tissues). |
| Bioavailability | Oral bioavailability: Norethindrone ~60-70% (due to first-pass metabolism); Ethinyl estradiol ~50-60% (susceptible to CYP3A4-induced metabolism). |
| Onset of Action | Oral: Onset of contraceptive effect occurs after 7 days of continuous dosing; peak serum concentrations for both components reached at 1-2 hours post-dose. |
| Duration of Action | Duration of contraceptive efficacy is 24 hours with once-daily dosing. Missed pills >12 hours reduce reliability. |
One tablet (norethindrone 1 mg/ethinyl estradiol 35 mcg) orally once daily for 21 days, followed by 7 days of placebo or no medication. Continuous sequential regimen.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended; use with caution in patients with renal impairment as limited data available. |
| Liver impairment | Contraindicated in Child-Pugh class B or C (moderate to severe hepatic impairment). For Child-Pugh class A, use with caution; no specific dose adjustment recommended. |
| Pediatric use | Use only after menarche; same dosing as adults (one tablet daily for 21 days, then 7 days off). Not indicated for premenarchal patients. |
| Geriatric use | Not typically used in postmenopausal women; no safety and efficacy established in geriatric population. Contraindicated in women over 35 who smoke heavily (≥15 cigarettes/day). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NYLIA 1/35 (NYLIA 1/35).
| Breastfeeding | Norethindrone/ethinyl estradiol passes into breast milk; M/P ratio not established. May reduce milk production and alter composition. Use during breastfeeding not recommended; consider using progestin-only contraceptives if needed. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: Increased risk of neural tube defects, congenital heart defects, and limb reduction defects due to progestin/estrogen exposure. Second and third trimesters: Risk of masculinization of female fetuses (progestin-induced pseudohermaphroditism) and potential for estrogen-related adverse effects; contraindicated in pregnancy. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use. Risk increases with age and heavy smoking (≥15 cigarettes/day) and is most significant in women over 35 years. Women who use combination oral contraceptives should be strongly advised not to smoke.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease (current or history)","Known or suspected breast carcinoma","Estrogen-dependent neoplasia (known or suspected)","Undiagnosed abnormal genital bleeding","Pregnancy (known or suspected)","Hepatic adenoma or carcinoma (current or history)","Jaundice or liver disease with impaired function (acute or chronic)","Hypersensitivity to any component of the product"]
| Precautions | ["Thrombotic disorders (venous thromboembolism, arterial thromboembolism, stroke, myocardial infarction): discontinue if signs/symptoms occur","Cigarette smoking increases risk of serious cardiovascular events","Increased risk of gallbladder disease","Hepatic neoplasia (benign and malignant) – discontinue if jaundice or liver abnormalities develop","Hypertension – monitor blood pressure","Glucose intolerance – monitor in diabetic patients","Headache/migraine – discontinue if new or worsening","Bleeding irregularities (breakthrough bleeding, amenorrhea)","Depression – discontinue if severe"] |
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| Fetal Monitoring | Monitor for pregnancy status prior to initiation and during therapy (urine or serum hCG). Monitor for signs of thromboembolism, hypertension, and liver dysfunction in the mother. Fetal monitoring if inadvertent exposure occurs. |
| Fertility Effects | Transient suppression of ovulation upon initiation; rapid return to baseline fertility upon discontinuation. No long-term adverse effects on fertility. |