CYCLAFEM 7/7/7
Clinical safety rating
cautionComprehensive clinical and safety monograph for CYCLAFEM 7/7/7 (CYCLAFEM 7/7/7).
Combination estrogen-progestin contraceptive. Ethinyl estradiol suppresses gonadotropin release (FSH, LH) via negative feedback on hypothalamic-pituitary axis; norethindrone induces endometrial changes that inhibit implantation and thickens cervical mucus.
| Metabolism | Primarily hepatic via CYP3A4 hydroxylation and conjugation; ethinyl estradiol undergoes first-pass metabolism and enterohepatic recirculation. Norethindrone is metabolized to various reduced and conjugated metabolites. |
| Excretion | Renal: ~50-60% as conjugated metabolites; Fecal: ~30-40% via bile; <1% unchanged. |
| Half-life | Terminal half-life: 5-13 hours (mean 8 hrs); clinical context: supports every-28-day dosing interval for intramuscular depot. |
| Protein binding | ~97-99% bound, primarily to sex hormone-binding globulin (SHBG) and albumin. |
| Volume of Distribution | 2.5-4.5 L/kg; extensive tissue distribution including adipose tissue, brain, and reproductive organs. |
| Bioavailability | Oral: ~100% (combination with ethinyl estradiol enhances absorption); IM: 100% (depot formulation). |
| Onset of Action | IM depot: maximal plasma concentrations reached within 3-5 days; contraceptive effect established within 24 hours for oral route. |
| Duration of Action | IM depot: effective contraception for at least 28 days; oral: 24 hours per daily dose. |
| Molecular Weight | 312.4 |
| Action Class | Oral Contraceptive; Estrogen-Progestin Combination |
One tablet (norethindrone 0.5 mg/ethinyl estradiol 35 mcg) orally once daily for 7 days, then one tablet (norethindrone 0.75 mg/ethinyl estradiol 35 mcg) orally once daily for 7 days, then one tablet (norethindrone 1 mg/ethinyl estradiol 35 mcg) orally once daily for 7 days. Dispensed in a 21-tablet pack with 7 placebo tablets. For contraception, take one tablet daily at same time each day for 28 days; begin next pack after 28-day cycle.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (GFR <30 mL/min); use is not recommended due to potential hormonal accumulation and increased thrombotic risk. |
| Liver impairment | Contraindicated in acute or chronic hepatic dysfunction (Child-Pugh class B or C) due to impaired metabolism of estrogen and progestin. For mild hepatic impairment (Child-Pugh class A), limited data; use alternative contraception if possible. |
| Pediatric use | Safety and efficacy not established in females younger than 18 years for contraception; however, postmenarchal adolescents may use standard adult dosing (after menarche). Weight-based dosing not applicable; use weight ≥45 kg with no dose adjustment. For other indications (e.g., acne), follow adult dosing in patients ≥15 years. |
| Geriatric use | Not indicated for postmenopausal women (age >55 years) as no contraceptive benefit. If used off-label, no specific dose adjustment; however, consider increased risk of cardiovascular events (thrombosis, hypertension, stroke) and metabolic effects (glucose intolerance, lipid changes) in older women with additional risk factors. Use lowest effective dose if necessary. |
| 1st trimester | Contraindicated due to risk of fetal harm (oral contraceptive use in early pregnancy is not recommended; if pregnancy occurs, discontinue immediately). |
| 2nd trimester | Contraindicated; estrogen/progestin combinations may cause fetal harm and are not indicated during pregnancy. |
| 3rd trimester | Contraindicated; avoid use in pregnancy due to potential adverse effects on fetus. |
Clinical note
Comprehensive clinical and safety monograph for CYCLAFEM 7/7/7 (CYCLAFEM 7/7/7).
| Placental transfer | Estrogens and progestins cross the placenta. Evidence of transfer with measurable fetal serum levels. |
| Breastfeeding | Estrogens and progestins are excreted in breast milk in small amounts; may reduce milk production and composition. Use lowest effective dose if necessary, but generally not recommended during breastfeeding. |
| Lactation Rating | L3 (Limited data; potential risk) |
| Teratogenic Risk | Pregnancy Category X. First trimester: Major birth defects including neural tube defects, cardiovascular malformations, and oral clefts. Second/third trimester: Fetal demasculinization in males, potential for feminization. Post-natal: Long-term reproductive tract abnormalities. |
| Fetal Monitoring | Maternal: Blood pressure, liver function, glucose tolerance, lipid profile. Fetal: Ultrasound for structural anomalies in first trimester; growth scans in third trimester if prolonged exposure. |
| Fertility Effects | Suppresses ovulation; reversible upon discontinuation. May delay return to fertility by 1-3 months. No permanent impact on fertility. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events (myocardial infarction, thromboembolism, stroke) from combination oral contraceptive use, especially in women >35 years and those who smoke ≥15 cigarettes/day.
| Common Effects | Nausea, Headache, Breast tenderness, Weight changes, Irregular bleeding or spotting, Mood changes |
| Serious Effects | Venous thromboembolism (deep vein thrombosis, pulmonary embolism), Arterial thromboembolism (myocardial infarction, stroke), Hepatic adenoma or hepatocellular carcinoma, Hypertension, Gallbladder disease, Optic neuritis or retinal thrombosis |
Thrombophlebitis or thromboembolic disordersHistory of deep vein thrombosis or pulmonary embolismCerebrovascular diseaseCoronary artery diseaseKnown or suspected pregnancyUndiagnosed abnormal genital bleedingKnown or suspected breast cancerKnown or suspected estrogen-dependent neoplasiaHepatic adenoma or carcinomaActive liver disease or impaired liver functionSmoking in women over age 35Migraine with focal auraDiabetes with vascular involvementUncontrolled hypertension
| Precautions | Thromboembolic disorders (DVT, PE, stroke, MI) – discontinue if symptoms occur, Hepatic disease (jaundice, hepatitis, cholestasis) – discontinue if develops, Hypertension – monitor blood pressure; discontinue if uncontrolled, Gallbladder disease – increased risk of cholelithiasis, Carbohydrate/lipid metabolism – monitor in diabetic or hyperlipidemic patients, Headache (including migraine) – discontinue if new or worsening, Uterine bleeding – rule out pregnancy if amenorrhea occurs, Depression – discontinue if severe, Ocular lesions (retinal thrombosis) – discontinue if visual disturbances occur |
| Food/Dietary | No specific dietary restrictions are required. Grapefruit and grapefruit juice may modestly increase ethinyl estradiol levels, but this is not considered clinically relevant in most cases. Avoid excessive grapefruit intake to be cautious. The medication can be taken with or without food. High-fat meals may delay absorption of the hormones, but overall contraceptive efficacy is not affected. |
| Clinical Pearls | Cyclafem 7/7/7 is a triphasic combined oral contraceptive containing ethinyl estradiol and norethindrone. The varying hormone doses across the three 7-day phases mimic the natural menstrual cycle. It is essential to start the first pack on the first day of menses for immediate contraceptive efficacy. Missed pills require specific instructions based on the week; if one pill is missed, take it as soon as remembered and continue. If two pills are missed in week 1 or 2, take two pills for two days, then resume. If two pills are missed in week 3, or three or more pills are missed at any time, use backup contraception for 7 days and consider starting a new pack. Breakthrough bleeding is common, especially in the first few cycles, and does not indicate contraceptive failure. Grapefruit juice may increase ethinyl estradiol levels, but clinical significance is minimal; still, avoid excessive intake. |
| Patient Advice | Take one pill daily at the same time each day, following the order of the pills in the pack (7 light yellow, 7 orange, 7 light green, then 7 white placebo). · If you miss a pill, refer to the package insert instructions based on how many pills you missed and the week you are in; use backup contraception if needed. · Common side effects include nausea, breast tenderness, and breakthrough bleeding, especially in the first 3 cycles; report severe symptoms. · Smoking increases the risk of serious cardiovascular side effects, especially in women over 35; do not smoke while on this medication. · Not all women can use combination oral contraceptives; inform your doctor if you have a history of blood clots, migraines with aura, liver disease, or certain cancers. · Use backup contraception (e.g., condoms) for the first 7 days if starting for the first time or after a break of more than 7 days. · Missed pills, vomiting, or diarrhea may reduce effectiveness; follow instructions for missed pills and use backup contraception. |
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