Japanese drugmaker Kissei Pharmaceutical has been ordered by the country’s Health Ministry to add a warning to the package insert of Tavneos (avacopan), a medication for vasculitis, or blood vessel inflammation, after the deaths of 20 patients, reports The Japan Times.
It has also warned against newly administering the drug to patients.
The medication had been flagged by the Food & Drug Administration in March, which wanted it pulled from the market – but the drug company refused to withdraw the treatment.
Kissei was instructed to stipulate that patients have died from liver dysfunction after the use of the drug: it was launched in Japan in June 2022, with its package insert citing liver dysfunction as a possible serious side effect.
It is estimated to have been administered to 12 000 to 13 000 patients in the country. All 20 patients who died developed liver dysfunction, and 210 similar side effect reports have been made, including suspected cases.
The additional warning on the package insert says: “Serious liver dysfunction, such as vanishing bile duct syndrome (VBDS), may occur, and there have been reported cases of death.”
It also suggests doctors conduct regular liver function tests on patients who use the drug, and to stop its use if liver function abnormality appears.
The ministry said the 20 patients were men and women in their 60s to 90s and that VBDS was observed in 13 of them. Other side effects, including acute liver failure and liver function abnormality, were also observed.
The warning follows the advisory from the FDA about “serious post-marketing cases, including fatal cases, of drug-induced liver injury (DILI) associated with Tavneos”.
“Although hepatotoxicity is a serious adverse reaction for Tavneos identified in pre-market clinical trials and described in product labelling, VBDS and DILI cases with fatal outcomes represent new safety concerns. FDA is continuing to monitor cases of DILI, including VBDS, involving Tavneos and will provide updates as appropriate.”
In the US, the FDA’s review of post-marketing data globally until October 2024 turned up 76 DILI cases with enough evidence to suggest a causal link to avacopan, including 54 hospitalisations and five US cases. Median time to DILI onset was 46 days (range 22-140).
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