CYCLESSA
Clinical safety rating
cautionComprehensive clinical and safety monograph for CYCLESSA (CYCLESSA).
Combination of estrogen (ethinyl estradiol) and progestin (desogestrel) inhibits ovulation by suppressing gonadotropin release, increases viscosity of cervical mucus to impede sperm penetration, and alters endometrial receptivity.
| Metabolism | Ethinyl estradiol is metabolized primarily via CYP3A4; desogestrel is converted to active metabolite etonogestrel via CYP2C9 and CYP2C19. |
| Excretion | Urine (50-60% as metabolites, <10% unchanged); feces (30-40% as metabolites); enterohepatic circulation. |
| Half-life | Desogestrel: 38±13 hours (terminal); ethinyl estradiol: 14±3 hours (terminal). Steady-state reached after 7-10 days. |
| Protein binding | Desogestrel: 99.7% (SHBG); ethinyl estradiol: 98.5% (albumin, SHBG). |
| Volume of Distribution | Desogestrel: 1.0-1.5 L/kg (extensive tissue distribution); ethinyl estradiol: 0.15-0.35 L/kg (limited). |
| Bioavailability | Desogestrel: 76% (oral); ethinyl estradiol: 55% (oral, variable due to first-pass metabolism). |
| Onset of Action | Oral: 2-6 hours for contraceptive effect (inhibition of ovulation at steady-state). |
| Duration of Action | 24 hours (requires daily dosing); suppression of ovulation persists for 4-7 days after last dose. |
| Molecular Weight | Ethinyl estradiol: 296.4 Da; Desogestrel: 310.5 Da |
One tablet (0.15 mg desogestrel/0.02 mg ethinyl estradiol) orally once daily for 21 days, followed by 7 days of placebo.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Insufficient data for severe impairment (CrCl <30 mL/min); use with caution. |
| Liver impairment | Contraindicated in Child-Pugh class C (severe hepatic impairment). For mild to moderate (Child-Pugh A or B), use with caution: reduce estrogen dose or discontinue if intolerance occurs. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, dose same as adults: 0.15 mg desogestrel/0.02 mg ethinyl estradiol daily. |
| Geriatric use | Not indicated for postmenopausal women. No studies in geriatric population; use not recommended due to lack of benefit and increased thromboembolic risk with age. |
| 1st trimester | Pregnancy category X. Avoid use in pregnant women due to risk of fetal harm. Oral contraceptives are associated with fetal anomalies and adverse outcomes. |
| 2nd trimester | Pregnancy category X. Avoid use in pregnant women due to risk of fetal harm. Oral contraceptives are not indicated during pregnancy. |
| 3rd trimester | Pregnancy category X. Avoid use in pregnant women due to risk of fetal harm. Oral contraceptives are not indicated during pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for CYCLESSA (CYCLESSA).
| Placental transfer | Drug crosses the placenta. Ethinyl estradiol and desogestrel/etonogestrel are transferred to fetal circulation with measurable concentrations. |
| Breastfeeding | Cyclesa (ethinyl estradiol/desogestrel) is excreted in breast milk. Estrogens and progestins may reduce milk production and quality. Use with caution in lactating women; alternative contraception may be preferred. |
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | First trimester: The use of combined hormonal contraceptives containing desogestrel and ethinyl estradiol is not associated with an increased risk of major birth defects. Discontinuation due to first-trimester exposure is not indicated. Second and third trimesters: Prolonged exposure to estrogen-progestin combinations has been associated with rare risks such as congenital heart defects and limb reduction defects in case-control studies, but absolute risk is low. Fetal risk from inadvertent use in pregnancy is minimal; termination not recommended. |
| Fetal Monitoring | No specific fetal monitoring required for routine use. If used inadvertently during pregnancy, no additional surveillance is needed. Standard prenatal care is sufficient. |
| Fertility Effects | CYCLESSA is used for contraception and does not cause permanent infertility. After discontinuation, normal fertility returns; there is no delay in conception beyond the expected hormonal recovery period (typically within one to three menstrual cycles). No adverse effects on future fertility have been documented. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combined hormonal contraceptives. Risk increases with age and amount smoked (especially in women >35 years who smoke). Women should not use CYCLESSA if they smoke cigarettes and are over 35 years old.
| Serious Effects |
History of or current venous thromboembolismCerebrovascular or coronary artery diseaseUncontrolled hypertensionActive liver disease or hepatic tumorsKnown or suspected pregnancyBreast cancer or other estrogen-sensitive neoplasiaHeavy smoking (≥15 cigarettes/day) in women >35 years of ageMigraine with focal aura in women >35 years of age
| Precautions | Thrombotic disorders (venous thromboembolism, arterial thromboembolism), Cerebrovascular disease, Cardiovascular disease including myocardial infarction, Liver disease including hepatic adenoma, Increased blood pressure, Gallbladder disease, Carbohydrate and lipid metabolism effects, Headache, Bleeding irregularities |
| Food/Dietary | No significant food interactions. Grapefruit juice may slightly increase estrogen levels but not clinically relevant. Alcohol does not affect efficacy but may increase risk of liver damage with high doses. |
| Clinical Pearls | CYCLESSA (desogestrel/ethinyl estradiol) is a monophasic oral contraceptive. It may be used off-label for acne treatment. Breakthrough bleeding is common in the first 3 cycles. CYP3A4 inducers (e.g., rifampin) reduce efficacy; consider backup contraception. |
| Patient Advice | Take one tablet daily at the same time, even if no intercourse. · Start on the first day of menstrual period or first Sunday after period starts. · Use backup contraception for first 7 days if starting after day 5. · Missed pill: take as soon as remembered. If more than 2 missed, use backup method. · Vomiting or diarrhea may reduce effectiveness. · Report unexplained leg pain, chest pain, severe headache, or vision changes. · Smoking increases risk of serious cardiovascular side effects, especially if over 35. |
Loading safety data…