What it's for (Indications)
- Bosentan monohydrate is indicated for the treatment of Pulmonary Arterial Hypertension (PAH) to improve exercise capacity and symptoms in patients with WHO functional class II and III.
- It is also used to reduce the number of new digital ulcers in patients with systemic sclerosis with ongoing digital ulcer disease.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | For patients older than 12 years of age, initiate treatment at 62.5 mg orally twice daily. For patients weighing greater than 40 kg, the dose should be increased to 125 mg orally twice daily after 4 weeks. For patients 12 years of age and younger, dosage is weight-based. Dose reduction and close monitoring are required for patients developing aminotransferase elevations greater than 3 times the Upper Limit of Normal (ULN). Treatment should be withdrawn gradually. |
Safety & Warnings
Common Side Effects
- Common adverse reactions include upper respiratory tract infections, pyrexia (fever), headaches, flushing, dyspnoea, gastrointestinal upset, erythema, dermatitis, pain in extremity, back pain, and peripheral edema (fluid retention).
- Other reported adverse effects include anemia, infected skin ulcer, and urinary tract infections.
- Significant risks include hepatotoxicity and embryo-fetal toxicity.
Serious Warnings
- Black Box Warning: WARNING: RISKS OF HEPATOTOXICITY and EMBRYO-FETAL TOXICITY. Bosentan can cause significant elevations of liver aminotransferases (ALT/AST) and is teratogenic. Due to these risks, bosentan is available only through a restricted distribution program (e.g., Bosentan REMS Program in the US) that requires enrollment of prescribers, patients, and pharmacies, and compliance with mandatory monitoring, including monthly liver function tests and pregnancy tests.
- Patients should be advised of the risks of hepatotoxicity and embryo-fetal toxicity.
- Liver aminotransferase levels (ALT/AST) must be monitored regularly (e.
- g.
- , monthly); patients should report any signs suggestive of liver damage.
- Dose reduction and close monitoring are required for aminotransferase elevations >3x Upper Limit of Normal (ULN).
- Hemoglobin levels and signs of fluid retention (e.
- g.
- , peripheral edema) should be monitored.
- Females of reproductive potential must use two reliable forms of non-hormonal contraception during treatment and for one month after stopping bosentan, and require a negative pregnancy test prior to initiation, monthly during treatment, and one month after cessation.
- Treatment should be withdrawn gradually.
- In the US, bosentan is available only through a restricted program (Bosentan REMS Program) due to these risks, requiring enrollment and compliance with monitoring.
How it Works (Mechanism of Action)
Bosentan is a specific and competitive antagonist at endothelin receptor types ETA and ETB, with a slightly higher affinity for ETA receptors. It blocks the effects of Endothelin-1 (ET-1), a potent vasoconstrictor and neurohormone elevated in patients with PAH, which plays a pathogenic role in the disease.
Commercial Brands (Alternatives)
No other brands found for this formula.