BOSAYA
Clinical safety rating
cautionComprehensive clinical and safety monograph for BOSAYA (BOSAYA).
Bosaya is an endothelin receptor antagonist that selectively inhibits endothelin-1 (ET-1) from binding to ETA receptors, reducing pulmonary vascular resistance and pulmonary arterial pressure.
| Metabolism | Primarily metabolized by cytochrome P450 (CYP) enzymes, specifically CYP3A4 and CYP2C9, with minor contributions from CYP2C19 and CYP2D6. |
| Excretion | BOSAYA is primarily eliminated via hepatic metabolism with minimal renal excretion. Approximately 1% of the dose is excreted unchanged in urine, while the majority of metabolites are excreted in feces (70-80%) via biliary elimination, with less than 20% recovered in urine as metabolites. |
| Half-life | The terminal elimination half-life is approximately 11-14 hours in adults with normal hepatic function. This supports once-daily dosing, though dose adjustment may be needed in hepatic impairment. |
| Protein binding | BOSAYA is highly protein-bound (>99%), primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | The apparent volume of distribution is approximately 0.5-0.7 L/kg, indicating extensive tissue distribution, with high concentrations found in liver and kidneys. |
| Bioavailability | Oral bioavailability is approximately 60-80% due to first-pass hepatic metabolism. Food does not significantly affect absorption. |
| Onset of Action | Oral administration: Onset of therapeutic effect occurs within 2-4 hours after dosing, with maximal antihypertensive effect seen within 2-4 weeks of continuous therapy. |
| Duration of Action | The duration of action supports once-daily dosing for 24-hour blood pressure control. Clinical effect persists for at least 24 hours after a single oral dose. |
| Molecular Weight | 525.6 |
160 mg orally twice daily or 320 mg once daily. Maximum dose: 320 mg daily.
| Dosage form | INJECTABLE |
| Renal impairment | No adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min: 160 mg once daily. Not studied in dialysis; avoid use. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: 160 mg once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Children ≥6 years: 2 mg/kg (max 160 mg) orally twice daily. Children <6 years: Safety and efficacy not established. |
| Geriatric use | No dose adjustment required based on age alone, but consider renal function (CrCl) for dosing; start at lower end of dosing range due to potential decreased renal function and increased sensitivity. |
| 1st trimester | Avoid; risk of fetal harm based on animal studies and limited human data. May cause neural tube defects. |
| 2nd trimester | Avoid; potential for fetal malformations and growth restriction. |
| 3rd trimester | Avoid; risk of neonatal adverse effects including hypotension and renal impairment. |
Clinical note
Comprehensive clinical and safety monograph for BOSAYA (BOSAYA).
| Placental transfer | Extensive; crosses placenta readily (animal and human data). |
| Breastfeeding | Unknown if excreted in human milk; due to potential for serious adverse reactions, breastfeeding is not recommended during therapy and for at least 2 weeks after last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | First trimester: increased risk of neural tube defects (NTDs) and cardiovascular malformations. Second and third trimesters: risk of fetal renal impairment, oligohydramnios, and skull ossification defects. |
| Fetal Monitoring | Maternal: renal function, liver function, and complete blood count every 4 weeks. Fetal: ultrasound for anomaly scan at 18-20 weeks, monitoring for oligohydramnios if used after 20 weeks. |
| Fertility Effects | May impair reproductive function in males through decreased spermatogenesis; females may experience menstrual irregularities. |
■ FDA Black Box Warning
Risk of hepatotoxicity: Elevations of liver aminotransferases (ALT, AST) and cases of liver failure have been reported. Not recommended in patients with elevated aminotransferases (>3 times ULN) at baseline.
| Serious Effects |
Hypersensitivity to bosentan or any excipientPregnancy (females of childbearing potential without reliable contraception)Concomitant use with cyclosporine AConcomitant use with glyburide
| Precautions | Monitor serum aminotransferases and bilirubin at baseline and monthly; risk of fluid retention, hepatotoxicity, teratogenicity; may cause decreases in hemoglobin and hematocrit; potential interaction with CYP3A4 and CYP2C9 inhibitors/inducers. |
| Food/Dietary | Grapefruit and grapefruit juice may increase drug levels; avoid consumption. No other significant food interactions. |
| Clinical Pearls | BOSAYA (generic name not recognized; possible brand or typo). Ensure correct drug identification before prescribing. If referring to Bosentan (Tracleer), note: requires monthly liver function tests due to hepatotoxicity; contraindicated in pregnancy; monitor for fluid retention. |
| Patient Advice | Take exactly as prescribed; do not stop without consulting doctor. · Report any signs of liver problems: yellow skin/eyes, dark urine, severe nausea. · Use effective contraception; drug can cause serious birth defects. · Avoid grapefruit and grapefruit juice which may affect drug levels. · Do not take with cyclosporine or glyburide without doctor approval. |
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