CRYSELLE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CRYSELLE (CRYSELLE).
Cryselle is a combination oral contraceptive containing ethinyl estradiol and norgestrel. It inhibits ovulation by suppressing gonadotropin release, primarily through estrogenic and progestogenic effects on the hypothalamic-pituitary axis. It also increases cervical mucus viscosity and alters endometrial structure, impeding sperm penetration and implantation.
| Metabolism | Ethinyl estradiol undergoes first-pass metabolism in the gut wall and liver, primarily via CYP3A4, and is also involved in conjugation (glucuronidation and sulfation). Norgestrel is metabolized in the liver via reduction and conjugation, with the active isomer levonorgestrel undergoing hydroxylation by CYP3A4. |
| Excretion | Renal (50% as metabolites, 20% unchanged), fecal (30%), with enterohepatic recirculation. |
| Half-life | Terminal elimination half-life approximately 24 hours (range 16-36 h), with clinical significance for once-daily dosing. |
| Protein binding | 95-98% bound to serum albumin and sex hormone-binding globulin. |
| Volume of Distribution | Approximately 2 L/kg (40-60 L total), indicating extensive tissue distribution. |
| Bioavailability | Oral: 85-90% due to first-pass metabolism; otherwise 100% for IV. |
| Onset of Action | Oral: 1-2 hours (contraceptive effect), with suppression of ovulation achieved by day 7 of dosing. |
| Duration of Action | 24 hours with once-daily dosing; continuous therapy required for sustained contraceptive effect. |
One tablet (0.3 mg norgestrel/0.03 mg ethinyl estradiol) orally once daily at the same time each day for 21 consecutive days, followed by 7 days of placebo.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in patients with acute or chronic renal failure due to potential for fluid retention and electrolyte disturbances. |
| Liver impairment | Contraindicated in patients with Child-Pugh Class B or C cirrhosis or active liver disease. Use with caution in Child-Pugh Class A; consider alternative therapy if hepatotoxicity risk outweighs benefits. |
| Pediatric use | Not indicated for premenarchal girls. Postmenarchal adolescents: same dosing as adults (0.3 mg norgestrel/0.03 mg ethinyl estradiol once daily for 21 days, then 7 days placebo). |
| Geriatric use | Not indicated for use in postmenopausal women. No specific dosing adjustments recommended for elderly patients, but use with caution due to increased risk of thromboembolic events and cardiovascular disease. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CRYSELLE (CRYSELLE).
| Breastfeeding | Excreted in breast milk; M/P ratio approximately 0.1-0.5 for levonorgestrel and 0.02-0.1 for ethinyl estradiol. Combined hormonal contraceptives may reduce milk production and quality; use alternative contraception during breastfeeding. Not recommended while nursing. |
| Teratogenic Risk | CRYSELLE (levonorgestrel/ethinyl estradiol) is contraindicated in pregnancy. First trimester: no increased risk of major birth defects from inadvertent use, but postmarketing data limited. Second and third trimesters: associated with increased risk of fetal harm including cardiovascular and genital anomalies, and potential feminization of male fetuses due to progestin exposure. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. This risk increases with age and with heavy smoking (≥15 cigarettes per day) and is marked in women over 35 years of age. Women who use combination oral contraceptives should be strongly advised not to smoke.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease (current or history)","Known or suspected breast carcinoma","Endometrial carcinoma or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior pill use","Hepatic adenoma or carcinoma (current or history)","Known or suspected pregnancy","Hypersensitivity to any component","Heavy smoking (≥15 cigarettes/day) and age >35 years"]
| Precautions | ["Cardiovascular events (thrombophlebitis, venous thrombosis, arterial thromboembolism, myocardial infarction, stroke, pulmonary embolism)","Hepatic neoplasia (benign and malignant)","Gallbladder disease","Carbohydrate and lipid metabolism effects","Elevated blood pressure","Ocular lesions (retinal thrombosis)","Headache (including migraine with focal symptoms)","Irregular bleeding","Depression","Lactation (may decrease milk production)","Hereditary angioedema exacerbation","Chloasma"] |
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| Fetal Monitoring | Not applicable during pregnancy as drug is contraindicated. If inadvertent exposure occurs, monitor fetal development via ultrasound and follow routine prenatal care. Assess for pregnancy before initiating therapy. |
| Fertility Effects | CRYSELLE is a contraceptive; intended to prevent pregnancy. No evidence of permanent fertility impairment upon discontinuation; normal fertility typically resumes within 1-3 months after cessation. |