New communication emphasises advice about hepatic monitoring to combat known concerns with ANCA-associated vasculitis drug.
A new communique from the US Food and Drug Administration (FDA) has emphasised the importance of liver function test monitoring for avacopan, given the rare risk of drug-induced liver injury, including vanishing bile duct syndrome.
The US regulator has now given more explicit advice about monitoring intervals for patients starting on avacopan, which is used as a steroid-sparing agent in ANCA-associated vasculitis induction, and has quickly become standard-of-care in the relevant patient population in Australia.
Health care professionals managing patients on avacopan are now advised to “conduct liver panel testing every two weeks in the first month of treatment, monthly for the next five months, and then as clinically indicated”.
The advice also recommends promptly discontinuing avacopan when ALT or AST is greater than three times the upper limit of normal, ALP is greater than two times the upper limit of normal, or a patient “presents with evidence of symptomatic cholestasis such as jaundice or pruritus”.
This new guidance, released on March 31, is a slight advance on existing Australian advice from the Therapeutic Goods Administration (TGA), which advises that “treatment must be re-assessed clinically and temporarily stopped if alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is more than 3x the upper limit of normal”, and that “treatment must be temporarily stopped if ALT or AST is more than 5x the upper limit of normal”.
Vanishing bile duct syndrome is a rare side effect of avacopan which has previously been incorporated into regulatory advice, including from the TGA.
This most recent advice comes after the FDA reviewed their post-marketing surveillance database.
Notably, 66 of the 76 reported cases of drug-induced liver injury were from Japan, and only seven of them represented proven vanishing bile duct syndrome from avacopan.
Related
The FDA has specified it will continue to monitor post-marketing cases of drug-induced liver injury and will provide updates as appropriate.
These updates come on the background of public pressure on the FDA in the United States in the context of recent changes in policy, with advocates worried that regulatory changes are closing options for rare diseases, the New York Times reported.
