Dosage of Bosentan

Recommended Dosage

Take bosentan orally in accordance with the following recommended dosages. Doses higher than 125 mg twice daily do not appear to provide additional benefits sufficient to offset the increased risk of hepatotoxicity.

Patients aged 12 years and older with a body weight > 40 kg: The initial dose is 62.5 mg taken orally twice daily; after 4 weeks, increase to 125 mg taken orally twice daily.

Patients aged 12 years and older with a body weight < 40 kg: The initial dose is 62.5 mg taken orally twice daily; the maintenance dose is 62.5 mg taken orally twice daily.

Patients aged 12 years and younger: Dosage is based on body weight.

Patients with a body weight of 4–8 kg: 16 mg twice daily.

Patients with a body weight of > 8–16 kg: 32 mg twice daily.

Patients with a body weight of > 16–24 kg: 48 mg twice daily.

Patients with a body weight of > 24–40 kg: 64 mg twice daily.

Administration

Bosentan film-coated tablets and tablets for oral suspension (dispersible tablets) should be administered orally twice daily.

Half of a tablet for oral suspension or a dispersible tablet should be dispersed in a small amount of water immediately before administration.

Split dispersible tablet segments can be stored in the opened blister at 20°C to 25°C (68°F to 77°F) for a maximum of 7 days.

Dosage Adjustment for Elevated Aminotransferases

If aminotransferase levels are elevated, adjust the monitoring and treatment plan according to the following recommendations. Discontinue bosentan if elevated hepatic aminotransferases are accompanied by clinical signs of hepatotoxicity (e.g., nausea, vomiting, fever, abdominal pain, jaundice, or unusual somnolence or fatigue) or if bilirubin is ≥ 2 times the upper limit of normal (ULN). There is no experience with reintroducing bosentan in such cases.

If ALT/AST levels are > 3 × ULN and ≤ 5 × ULN: Confirm with another aminotransferase test. If confirmed:

In adults and pediatric patients aged 12 years and older with a body weight > 40 kg: Reduce the daily dose to 62.5 mg twice daily or interrupt treatment, and monitor aminotransferase levels at least every 2 weeks. If aminotransferase levels return to pretreatment values, treatment can be continued or reinitiated at 62.5 mg twice daily, and aminotransferase levels should be reassessed within 3 days.

In all other pediatric patients: Interrupt treatment without prior dose reduction. If aminotransferase levels return to pretreatment values, reinitiate treatment at the dose used before treatment interruption, and reassess aminotransferase levels within 3 days.

If ALT/AST levels are > 5 × ULN and ≤ 8 × ULN: Confirm with another aminotransferase test. If confirmed:

Discontinue treatment and monitor aminotransferase levels at least every 2 weeks. Once aminotransferase levels return to pretreatment values:

In adults and pediatric patients aged 12 years and older with a body weight > 40 kg: Consider reinitiating treatment at 62.5 mg twice daily, and reassess aminotransferase levels within 3 days.

In all other pediatric patients: Consider reinitiating treatment at the dose used before treatment interruption, and reassess aminotransferase levels within 3 days.

If ALT/AST levels are > 8 × ULN: Permanently discontinue treatment. There is no experience with reintroducing bosentan in such cases.

FDA，2025.07