Silkay Dosage/Direction for Use

Adult & Geriatric: Pulmonary artery hypertension: Oral: <40 kg: Initial and maintenance: 62.5 mg twice daily.
≥40 kg: Initial: 62.5 mg twice daily for 4 weeks; increase to maintenance dose of 125 mg twice daily.
Doses >125 mg twice daily do not appear to confer additional clinical benefit but may increase risk of liver toxicity.
Note: When discontinuing treatment, consider a reduction in dosage to 62.5 mg twice daily for 3 to 7 days (to avoid clinical deterioration).
Missed doses: If a dose is missed, administer as soon as remembered; if it is almost time for the next dose, take at the usual scheduled time. Do not administer a double dose to make up for a missed dose.
Coadministration with ritonavir (US labeling): Oral: Note: the Canadian labeling recommends the following dose adjustments with coadministration of any protease inibitor): Dosage adjustment for concurrent use with ritonavir: Coadministration of bosentan in patients currently receiving ritonavir for at least 10 days: Begin with bosentan 62.5 mg once daily or every other day based on tolerability.
Coadministration of ritonavir in patients currently receiving bosentan: Discontinue bosentan 36 hours prior to initiation of ritonavir. After at least 10 days of the protease inhibitor regimen, resume bosentan 62.5 mg once daily or every other day based on tolerability.
Pediatric: Pulmonary artery hypertension: Oral: US labeling: Children >12 years and Adolescents: Refer to adult dosing.
Canadian labeling: Children ≥3 years and Adolescents (based on limited data): 10 to 20 kg: Initial: 31.25 mg once daily for 4 weeks: increase to maintenance dose of 31.25 mg twice daily.
Renal impairment: No dosage adjustment necessary. Bosentan is unlikely to be removed by dialysis (due to high molecular weight and extensive plasma protein binding).
Hepatic impairment: Hepatic impairment of treatment initiation: Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate to severe impairment (Child-Pugh class B and C) and/or baseline transaminase >3 times ULN; Use should be avoided; systemic exposure is significantly increased in patients with moderate impairment (not studied in patients with severe impairment).
Hepatotoxicity during treatment: Modification based on transaminase elevation: Transaminase elevations accompanied by clinical symptoms of hepatic injury (unusual fatigue, nausea, vomiting, abdominal pain, fever, or jaundice) or a serum bilirubin ≥2 times ULN; Discontinue treatment.
AST/ALT >3 times but ≤5 times ULN: Confirm with additional tests; if confirmed, reduce dose to 62.5 mg twice daily or interrupt treatment and monitor at least every 2 weeks. If transaminase levels return to pre-treatment values, may continue or reintroduce treatment (at the starting dose), as appropriate. When reintroducing treatment, recheck transaminases within 3 days and at least every 2 weeks thereafter.
AST/ALT >5 times but ≤8 times ULN: Confirm with additional test; if confirmed, stop treatment. Monitor transaminase levels at least every 2 weeks. If transaminase levels return to pretreatment values, may reintroduce treatment (at the starting dose) as appropriate. Following reinitiation, recheck within 3 days and at least every 2 weeks thereafter.
AST/ALT >8 times ULN: Stop treatment and do not reintroduce.
Dietary Considerations: Avoid grapefruit and grapefruit juice.
Administration: May be administered with or without food, once in the morning and once in the evening.
Dosage forms: Tablet, Oral: 125 mg.