CYCLAFEM 1/35
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 312.4 (norethindrone: 298.42; ethinyl estradiol: 296.40) |
| Action Class | Oral Contraceptive; Estrogen-Progestin Combination |
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 | Contraindicated due to risk of teratogenicity (e.g., cardiovascular defects, neural tube defects) associated with estrogen-progestin combinations. |
| 2nd trimester | Not recommended; may increase risk of intrauterine growth restriction and fetal demise. |
| 3rd trimester | Not recommended; may increase risk of preterm birth, fetal demise, and neonatal complications. |
Clinical note
Comprehensive clinical and safety monograph for CYCLAFEM 1/35 (CYCLAFEM 1/35).
| Placental transfer | Estrogen and progestin components cross the placenta readily. Concentrations in fetal blood are similar to maternal levels. |
| Breastfeeding | Cyclafem 1/35 may reduce milk production and quality. Small amounts of hormones pass into breast milk but are not expected to cause harm at typical doses. Use only if clearly needed and with caution. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ 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.
| Common Effects | Nausea, Vomiting, Headache, Breast tenderness, Breakthrough bleeding or spotting, Weight changes, Mood changes, Acne |
| Serious Effects | Venous thromboembolism (deep vein thrombosis, pulmonary embolism), Arterial thromboembolism (myocardial infarction, stroke), Hepatic adenoma or hepatocellular carcinoma, Hypertension, Gallbladder disease, Thrombotic thrombocytopenic purpura (TTP), Hemolytic uremic syndrome (HUS) |
Thrombophlebitis or thromboembolic disordersCerebrovascular or coronary artery diseaseKnown or suspected breast cancerEstrogen-dependent neoplasiaUndiagnosed abnormal genital bleedingPregnancyHepatic adenoma or carcinomaPast or current liver tumorsHypersensitivity to any component
| 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 |
| Food/Dietary | No significant food interactions. However, grapefruit juice may increase ethinyl estradiol levels via CYP3A4 inhibition, though clinical significance is uncertain. Avoid excessive alcohol intake as it may impair liver function and reduce contraceptive efficacy. Maintain a balanced diet, as folate supplementation may be beneficial due to potential folate depletion with oral contraceptives. |
| Clinical Pearls | CYCLAFEM 1/35 is a monophasic oral contraceptive containing norethindrone (1 mg) and ethinyl estradiol (35 mcg). For missed pills: if one pill is missed, take it as soon as remembered, even if it means taking two pills in one day. If two pills are missed in Week 1 or 2, take two pills on the day remembered and two the next day, then resume regular schedule; use backup contraception for 7 days. If two pills are missed in Week 3 or three or more pills are missed at any time, discard the rest of the pack and start a new pack that day; use backup contraception for 7 days. Monitor for breakthrough bleeding, which is common in the first few cycles. Avoid use in women with uncontrolled hypertension, migraine with aura, or history of thromboembolism. |
| Patient Advice | Take one tablet daily at the same time each day; do not skip doses. · If you miss a pill, refer to the missed pill instructions in the package insert or consult your healthcare provider. · Use additional non-hormonal contraception (e.g., condoms) for 7 days after missing pills as directed. · Report any signs of thromboembolism (leg pain, chest pain, shortness of breath) or stroke (sudden severe headache, visual changes, speech difficulty) immediately. · Smoking increases the risk of serious cardiovascular side effects; avoid smoking while taking this medication. · This medication does not protect against HIV or other sexually transmitted infections. · Expect spotting or light bleeding between periods, especially in the first few months. · If you have vomiting or diarrhea, use backup contraception and consult your healthcare provider. |
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