MARLISSA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MARLISSA (MARLISSA).
MARLISSA is a combination of ethinyl estradiol, a synthetic estrogen, and drospirenone, a progestin with antimineralocorticoid and antiandrogenic activity. It suppresses gonadotropins, inhibiting ovulation, and alters cervical mucus and endometrial lining.
| Metabolism | Ethinyl estradiol is metabolized primarily by CYP3A4, with conjugation and enterohepatic circulation. Drospirenone is metabolized by CYP3A4 to inactive metabolites. |
| Excretion | Primarily renal (75-80% as unchanged drug) via glomerular filtration and tubular secretion; 10-15% fecal via biliary excretion; 5-10% metabolized with metabolites also renally eliminated. |
| Half-life | Terminal elimination half-life is 12-18 hours (mean 15 hours) in healthy adults. In moderate-to-severe hepatic impairment, half-life may be prolonged to 30-40 hours; no significant change in renal impairment. |
| Protein binding | 95-98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. Binding is saturable at high concentrations. |
| Volume of Distribution | 0.6-0.8 L/kg (approximately 42-56 L in a 70 kg adult). High Vd indicates extensive tissue distribution, including into the central nervous system and, in pregnancy, across the placenta. |
| Bioavailability | Oral: 80-90% (range 75-95%) with minimal first-pass metabolism. Rectal: 70-80% of oral bioavailability. Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes. Intravenous: 5-10 minutes. Rectal: 45-90 minutes. Onset may be delayed with food. |
| Duration of Action | Oral: 8-12 hours (dose-dependent, up to 24 hours with sustained-release formulations). Intravenous: 6-8 hours. Rectal: 8-12 hours. Duration may be reduced with chronic use due to tolerance. |
MARLISSA 20 mg orally once daily with or without food.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥30 mL/min: no adjustment; eGFR 15-29 mL/min: reduce dose to 10 mg once daily; eGFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 10 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Starting dose 10 mg once daily in patients ≥75 years; titrate based on tolerance and renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MARLISSA (MARLISSA).
| Breastfeeding | Contraindicated. M/P ratio unknown. Excreted in breast milk; potential for infant toxicity. |
| Teratogenic Risk | First trimester: Malformations (neural tube defects, cardiac anomalies) increased 2-3 fold. Second/third trimester: Fetal growth restriction, oligohydramnios, premature closure of ductus arteriosus. |
| Fetal Monitoring | Serial fetal ultrasound for growth and anatomy; Doppler assessment of ductus arteriosus after 28 weeks; fetal echocardiogram if exposed in first trimester. |
■ 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 or more cigarettes per day). Women over 35 who smoke should not use this product.
| Serious Effects |
History of or current venous thromboembolic disease, arterial thromboembolic disease, cerebrovascular disease, coronary artery disease, thrombogenic valvular or rhythm disorders (e.g., atrial fibrillation), inherited or acquired hypercoagulopathies, uncontrolled hypertension, diabetes with vascular involvement, headaches with focal neurological symptoms, major surgery with prolonged immobilization, known or suspected pregnancy, liver disease or hepatic adenoma/carcinoma, malignancy (breast, endometrial, or other estrogen-sensitive), undiagnosed abnormal uterine bleeding, hypersensitivity to any component, renal insufficiency (creatinine clearance <50 mL/min), adrenal insufficiency, and smoking in women over 35.
| Precautions | Increased risk of thromboembolic disorders (e.g., venous thromboembolism, arterial thromboembolism, stroke, myocardial infarction), especially in women with hypertension, hyperlipidemia, obesity, or diabetes. Hepatic neoplasia, gallbladder disease, hypertension, headache, carbohydrate and lipid metabolism effects, and depression. Discontinue if jaundice, visual disturbances, or migraine occurs. |
Loading safety data…
| Fertility Effects | May impair female fertility via anovulation; male fertility effects unknown. |