ALYACEN 1/35
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALYACEN 1/35 (ALYACEN 1/35).
Combination hormonal contraceptive: ethinyl estradiol suppresses gonadotropin release via negative feedback on hypothalamic-pituitary axis; norethindrone induces progestational effects including cervical mucus thickening and endometrial changes, inhibiting ovulation and sperm penetration.
| Metabolism | Ethinyl estradiol: primarily hepatic via CYP3A4; norethindrone: hepatic reduction and sulfate conjugation. |
| Excretion | Renal excretion of metabolites (primarily ethinyl estradiol and norethindrone conjugates) accounts for approximately 50-60% of elimination; fecal excretion accounts for 30-40%. Unchanged drug excretion is minimal (<5%). |
| Half-life | Norethindrone: 8-11 hours (terminal); ethinyl estradiol: 10-20 hours (terminal). The half-life supports once-daily dosing for oral contraceptive efficacy. |
| Protein binding | Norethindrone: 61% bound to albumin and SHBG; ethinyl estradiol: 97-98% bound to albumin. |
| Volume of Distribution | Norethindrone: 3.8-4.5 L/kg; ethinyl estradiol: 2.0-4.0 L/kg. Large Vd indicates extensive tissue distribution. |
| Bioavailability | Oral: Norethindrone ~64%, ethinyl estradiol ~38-48% (due to first-pass metabolism). |
| Onset of Action | Oral: Contraceptive effect begins after 7 days of continuous dosing; for other hormonal effects (e.g., cycle control), onset occurs within the first cycle. |
| Duration of Action | Contraceptive protection lasts for 24 hours per daily dose; sustained hormonal effects require daily administration. |
| Molecular Weight | Ethinyl estradiol: 296.4 Da; Norethindrone: 298.4 Da. (Combination product: average molecular weight approximately 297.4 Da.) |
One tablet (norethindrone 1 mg and ethinyl estradiol 35 mcg) orally once daily for 21 consecutive days, followed by 7 days of placebo or no tablets.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment or acute renal failure due to potential fluid retention and electrolyte disturbances. |
| Liver impairment | Contraindicated in patients with hepatic impairment, including Child-Pugh class B or C, due to impaired metabolism of estrogen and progestin. Not recommended in patients with active liver disease or history of liver tumors. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults. Safety and efficacy established for contraception; weight-based dosing not applicable. |
| Geriatric use | Not indicated for use after menopause due to lack of benefit and increased risks (e.g., cardiovascular, thromboembolic events). If used, monitor for fluid retention, hypertension, and glucose intolerance. |
| 1st trimester | Contraindicated for use during pregnancy. Ethinyl estradiol and norethindrone exposure early in pregnancy has been associated with an increased risk of congenital anomalies, including cardiac defects and limb reduction. The product is not indicated for pregnancy prevention but may be used for contraception. |
| 2nd trimester | Contraindicated. Continued exposure may increase risk of adverse fetal outcomes; however, data are limited for second-trimester use beyond the period of organogenesis. |
| 3rd trimester | Contraindicated. Use during the third trimester may cause fetal harm, including masculinization of female fetuses due to progestin activity, and potential estrogenic effects on fetal development. |
Clinical note
Comprehensive clinical and safety monograph for ALYACEN 1/35 (ALYACEN 1/35).
| Placental transfer | Both ethinyl estradiol and norethindrone cross the placenta. Ethinyl estradiol is metabolized by the placenta, but active metabolites are transferred to the fetus. Norethindrone is known to readily cross the placenta and can be detected in fetal tissues. The degree of transfer is moderate to high, with fetal serum concentrations reaching up to 50% of maternal levels. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combined oral contraceptives. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use this product.
| Serious Effects |
Known or suspected pregnancyUndiagnosed abnormal genital bleedingKnown or suspected breast cancer or other estrogen-dependent neoplasiaActive thromboembolic disorder or history of deep vein thrombosis/pulmonary embolismCerebrovascular or coronary artery disease (current or history)Severe hepatic impairment or acute liver diseaseHepatocellular carcinoma or benign liver tumors (e.g., adenomas)Known hypersensitivity to any component of the productUse with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir, due to potential ALT elevations
| Precautions | Thrombotic disorders (e.g., DVT, PE, stroke, MI), Cerebrovascular disease, Hepatic neoplasia, Gallbladder disease, Hypertension, Carbohydrate and lipid effects, Ocular lesions, Hereditary angioedema, Chloasma, Menstrual irregularities, Pregnancy exclusion prior to initiation |
| Food/Dietary |
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| Breastfeeding | Small amounts of ethinyl estradiol and norethindrone are excreted in breast milk, potentially affecting the nursing infant. Norethindrone may reduce milk production and quality. Use is not recommended during breastfeeding due to possible adverse effects on the infant, including jaundice and breast enlargement. Alternative contraceptive methods should be considered unless benefits outweigh risks. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | Pregnancy category X. Use of ALYACEN 1/35 (norethindrone/ethinyl estradiol) is contraindicated during pregnancy. First trimester: Increased risk of congenital anomalies, including cardiovascular defects and limb reduction defects. Second/third trimesters: Potential for urogenital abnormalities and feminization of male fetus. Exposure is associated with subsequent development of clear cell adenocarcinoma of vagina/cervix in female offspring (DES-related). |
| Fetal Monitoring | Monitor for signs of thromboembolism, hypertension, hepatic dysfunction, and glucose intolerance. Regular blood pressure checks, liver function tests, and glucose screening. In case of inadvertent pregnancy, discontinue immediately and perform fetal anomaly ultrasound. |
| Fertility Effects | Reversible inhibition of ovulation. Fertility returns to baseline upon discontinuation. No long-term adverse effects on fertility documented. |
| No significant food interactions. Grapefruit juice may increase estrogen levels, but clinically not a concern. Avoid excessive alcohol, which may impair liver function and increase estrogen exposure. Maintain a healthy diet, as weight gain is possible. |
| Clinical Pearls | ALYACEN 1/35 is a combination oral contraceptive containing ethinyl estradiol 35 mcg and norgestimate 1 mg. It is indicated for the prevention of pregnancy and for the treatment of moderate acne vulgaris in females ≥15 years of age who desire an oral contraceptive. Monitor for thromboembolic events, especially in smokers over 35 or those with migraine with aura. Use with caution in patients with liver impairment or history of cholestatic jaundice. The pill-free interval should not exceed 7 days; missed pills increase ovulation risk. Consider non-hormonal backup if vomiting or diarrhea occurs within 4 hours of dosing. |
| Patient Advice | Take one tablet daily at the same time each day; do not skip doses. · Use an additional non-hormonal contraceptive (e.g., condoms) if you miss a pill, have vomiting, or diarrhea. · Smoking while on this pill increases the risk of blood clots and stroke, especially if you are over 35. · Contact your healthcare provider immediately if you have chest pain, leg pain/swelling, sudden vision changes, or severe headache. · This medication does not protect against HIV or other sexually transmitted infections. · Store at room temperature, away from moisture and heat. |