Table 7.

Monitoring and management of elevated liver enzymes for patients treated with bosentan

Liver function monitored at least monthly (fortnightly after initiation or dose escalation), with dose modification (if required) based on following protocol:
ALT/AST levels*	Treatment and monitoring recommendations §
<3 × ULN	Repeat
	Monitor fortnightly attend to potential other causes of elevation eg, concomitant medications, alcohol, biliary abnormalities
>3 and <5 × ULN	Repeat
	Reduce to starting dose or stop bosentan monitor ALT/AST at least fortnightly re-introduce at starting dose if pre-treatment levels are reached
>5 and <8 × ULN	Repeat
	Stop bosentan monitor ALT/AST at least fortnightly Re-introduce at starting dose if pre-treatment levels are reached
>8 × ULN	Repeat
	Stop permanently

^*Note: ALT, alanine transaminase

^§Bosentan should be stopped if any elevation > 3 × ULN in AST/ALT levels occur in association with rise in bilirubin to > 2 ×ULN and/or symptoms of liver dysfunction.

Abbreviations: AST, aspartate transaminase; ULN, Upper limit of normal