CYCLAFEM 7/7/7
Clinical safety rating: caution
Comprehensive 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. |
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 |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CYCLAFEM 7/7/7 (CYCLAFEM 7/7/7).
| Breastfeeding | Excreted in breast milk. M/P ratio ~0.2. Avoid breastfeeding due to potential estrogenic effects on infant. Alternative methods recommended. |
| 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 |
■ 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.
| Serious Effects |
["Smoking >15 cigarettes/day and age ≥35 years","History of DVT/PE or thromboembolic disorders","Cerebrovascular or coronary artery disease","Uncontrolled hypertension","Diabetes with vascular involvement","Migraine with focal aura (especially if >35 years)","Breast cancer (current or history)","Estrogen-dependent neoplasia","Liver tumors (benign or malignant) or active liver disease","Pregnancy or suspected pregnancy","Undiagnosed abnormal uterine bleeding","Use of ritonavir-boosted protease inhibitors (CYP3A4 induction reduces efficacy)"]
| 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"] |
Loading safety data…
| 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. |
| 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. |