CRYSELLE
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 312.45 |
| Action Class | Combination Oral Contraceptive (Estrogen-Progestin) |
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 | Contraindicated due to risk of birth defects; use only if benefits outweigh risks after counseling. |
| 2nd trimester | Contraindicated; associated with fetal harm, including cardiovascular and neural tube defects. |
| 3rd trimester | Contraindicated; may cause fetal harm, including feminization of male fetuses and potential long-term effects. |
Clinical note
Comprehensive clinical and safety monograph for CRYSELLE (CRYSELLE).
| Placental transfer | Crosses placenta readily; detectable in fetal plasma at levels similar to maternal. |
| Breastfeeding | Excreted in human milk; may cause adverse effects in nursing infants. Use only if clearly needed and with caution. Monitor infant for jaundice, drowsiness, and weight gain. |
| Lactation Rating | L3 (Moderately Safe) - limited data, use with caution. |
| 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. |
| 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. |
■ 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.
| Common Effects | Nausea, Headache, Breast tenderness, Weight changes, Irregular menstrual bleeding, Mood changes |
| 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) in patients with factor V Leiden mutation |
Known or suspected pregnancyUndiagnosed abnormal genital bleedingKnown or suspected breast cancerActive thromboembolic disordersHistory of thromboembolic disordersSevere hepatic impairmentHypersensitivity to any component
| 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 |
| Food/Dietary | No specific food interactions; however, grapefruit juice may increase estrogen levels slightly but clinical significance is minimal. St. John's Wort reduces contraceptive efficacy. High-fat meals can increase absorption of estrogen. |
| Clinical Pearls | Crysell is a combination oral contraceptive containing ethinyl estradiol and norgestrel. It is also used off-label for dysmenorrhea and endometriosis-associated pain. Monitor for hypertension, thromboembolic events, and hepatic adenoma. Smoking increases thromboembolism risk, especially in women over 35. Breakthrough bleeding common in first 3 cycles; if persistent, rule out pregnancy or missed pills. Altered efficacy with hepatic enzyme inducers (e.g., rifampin, carbamazepine). |
| Patient Advice | Take one tablet daily at the same time; do not skip doses. · Missed pills increase pregnancy risk; follow instructions in package insert. · Antibiotics (except rifampin) do not decrease effectiveness, but rifampin requires backup contraception. · Smoking while on this pill increases risk of blood clots, especially if over 35. · Report severe headaches, vision changes, chest pain, leg swelling or pain, or shortness of breath. · This does not protect against HIV or other STIs. · Breakthrough bleeding is common in first few months; contact provider if heavy or persistent. · If vomiting or diarrhea within 4 hours of a pill, take another pill and use backup contraception. |
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