CYCLAFEM 1/35
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CYCLAFEM 1/35 (CYCLAFEM 1/35).
Combination oral contraceptive containing ethinyl estradiol and norethindrone. Suppresses gonadotropin (FSH, LH) secretion via estrogen and progestin negative feedback, inhibiting ovulation. Progestin alters cervical mucus (sperm penetration) and endometrial receptivity.
| Metabolism | Ethinyl estradiol: CYP3A4, sulfation, glucuronidation. Norethindrone: CYP3A4, reduction, conjugation. |
| Excretion | Renal 40-60% as glucuronide and sulfate conjugates, biliary/fecal 20-40%. |
| Half-life | Half-life of norethindrone is 5-14 hours; ethinyl estradiol is 10-20 hours. Steady state reached after 5-7 days. |
| Protein binding | Norethindrone is 80-85% bound to SHBG and albumin; ethinyl estradiol is 95-98% bound to albumin. |
| Volume of Distribution | Norethindrone Vd is 1.2-2.4 L/kg; ethinyl estradiol Vd is 2.5-4.5 L/kg. |
| Bioavailability | Oral bioavailability: norethindrone 50-60%; ethinyl estradiol 40-50% due to first-pass metabolism. |
| Onset of Action | Oral: suppression of ovulation begins within 2-3 days of daily dosing. |
| Duration of Action | Duration of contraceptive effect is 24 hours per dose; withdrawal bleeding occurs 2-3 days after last active pill. |
One tablet orally once daily. Each tablet contains 1 mg norethindrone and 0.035 mg ethinyl estradiol. Administer daily for 21 days followed by 7 days of placebo or no tablet.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal disease or acute renal failure due to potential fluid retention. |
| Liver impairment | Contraindicated in Child-Pugh class B or C (moderate to severe hepatic impairment). For Child-Pugh class A, use with caution and monitor liver function; no specific dose adjustment studied. |
| Pediatric use | Not indicated for use in postmenarchal minors before menarche. For adolescents, same adult dosing (one tablet daily) after menarche. Safety and efficacy established in postmenarchal females. |
| Geriatric use | Not indicated for use in postmenopausal women. Avoid use in women over 50 years due to increased risk of thrombosis and no benefit for contraception. If used, no specific dose adjustment, but consider non-hormonal alternatives. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CYCLAFEM 1/35 (CYCLAFEM 1/35).
| Breastfeeding | Compatible with breastfeeding. Norethindrone and ethinyl estradiol are excreted in breast milk in small amounts. M/P ratio: Norethindrone ~0.5-0.7; ethinyl estradiol ~0.1-0.3. No adverse effects reported in infants at recommended doses. May reduce milk volume and protein content; use lowest effective dose. |
| Teratogenic Risk | Pregnancy category X. Contraindicated in pregnancy due to risk of fetal harm. First trimester: Increased risk of neural tube defects, cardiovascular anomalies, and limb reduction defects. Second and third trimesters: Associated with fetal genital abnormalities (masculinization of female fetuses) and potential for other congenital anomalies. Postnatal: Possible long-term neurodevelopmental effects. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from COC use. Risk increases with age and heavy smoking (>=15 cigarettes/day). Women over 35 who smoke should not use COCs.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders","History of DVT/PE","Cerebrovascular or coronary artery disease","Known or suspected breast carcinoma","Estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy/COC-related jaundice","Benign/malignant hepatic adenoma","Pregnancy","Hypersensitivity to any component","Age >35 and smoking >=15 cigarettes/day"]
| Precautions | ["Thrombotic disorders (DVT, PE, MI, stroke)","Hepatic neoplasia (benign and malignant)","Elevated blood pressure","Gallbladder disease","Carbohydrate/lipid metabolic effects","Hereditary angioedema exacerbation","Chloasma","Ocular lesions (retinal thrombosis, optic neuritis)","Depression","Menstrual irregularities/breakthrough bleeding"] |
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| Fetal Monitoring | Monitor for signs of pregnancy prior to initiation and at each visit. Perform pregnancy test if pregnancy suspected. During pregnancy (if inadvertent exposure), consider fetal ultrasound for anomalies and follow-up for neonatal outcomes. No routine monitoring required if not pregnant. |
| Fertility Effects | Suppresses ovulation, thereby preventing fertility. Return to fertility is usually rapid after discontinuation, with normal ovulatory cycles resuming within 1-3 months. No permanent negative effects on fertility reported. |