Bosentan

SOURCE: UK SPC for Bosentan 125 mg Film-coated Tablets (https://www.medicines.org.uk/emc/product/821/smpc). The dose above is for PULMONARY ARTERIAL HYPERTENSION. PRESCRIBING RESTRICTION: treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension; a Patient Alert Card is included in the pack. Bosentan should only be initiated if the systemic systolic blood pressure is higher than 85 mmHg. SECOND INDICATION — systemic sclerosis with ongoing digital ulcer disease (adults): the same regimen, 62.5 mg twice daily for 4 weeks then a maintenance dose of 125 mg twice daily; treatment should only be initiated and monitored by a physician experienced in the treatment of systemic sclerosis; controlled clinical study experience in this indication is limited to 6 months and the response to treatment and need for continued therapy should be re-evaluated regularly; there are no data on safety and efficacy under the age of 18 years in this indication. RE-INTRODUCTION: the same recommendations apply to re-introduction of bosentan after treatment interruption. LIVER MONITORING: liver aminotransferase levels must be measured prior to initiation and subsequently at monthly intervals for the duration of treatment, and 2 weeks after any dose increase. If ALT/AST >3 and <=5 x ULN, confirm by a second liver test and, if confirmed, decide individually whether to continue (possibly at a reduced dose) or stop, monitoring at least every 2 weeks; if >5 and <=8 x ULN, confirm and, if confirmed, stop treatment and monitor at least every 2 weeks; if >8 x ULN, treatment must be stopped and re-introduction is not to be considered. CLINICAL DETERIORATION: if the 6-minute walk test distance falls by at least 10% versus pre-treatment despite at least 8 weeks of treatment (target dose for at least 4 weeks), consider alternative therapies — though some patients showing no response at 8 weeks may respond after a further 4 to 8 weeks. DISCONTINUATION: to avoid possible rebound clinical deterioration, gradual dose reduction (halving the dose for 3 to 7 days) should be considered, with intensified monitoring during the discontinuation period; if withdrawing bosentan, do so gradually while an alternative therapy is introduced. HEPATIC IMPAIRMENT: contraindicated in moderate to severe liver dysfunction; no dose adjustment is needed in mild hepatic impairment (Child-Pugh class A). ELDERLY: no dose adjustment required over the age of 65 years. NEONATES: in persistent pulmonary hypertension of the newborn (PPHN) the benefit of bosentan has not been shown in the standard-of-care treatment and no recommendation on a posology can be made.

Applies to children with PULMONARY ARTERIAL HYPERTENSION aged 1 year and older, for whom 2 mg/kg morning and evening is stated as both the recommended starting dose and the maintenance dose. Verify against a children's formulary before prescribing. In neonates with persistent pulmonary hypertension of the newborn (PPHN) the benefit has not been shown and no recommendation on a posology can be made. There are no data on safety and efficacy under 18 years in the systemic sclerosis digital ulcer indication. In male children a long-term impact on fertility after treatment with bosentan cannot be excluded.