Serious liver injury, including fatal cases, has prompted updated monitoring and stopping rules for Tavneos (avacopan), the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has announced.

The updated measures address known risk for drug-induced liver injury and vanishing bile duct syndrome (VBDS) in adults with severe, active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). PRAC has endorsed a direct healthcare professional communication to inform clinicians of the updated recommendations.

About Tavneos 

Avacopan works by blocking the complement 5a receptor, inhibiting neutrophil activation and suppressing the small-vessel inflammation that drives GPA and MPA. The drug, available as 30-mg capsules taken twice daily with meals, requires both a prescription and specialist supervision, and carries orphan medicine designation for these rare conditions.

Beyond hepatotoxicity, common adverse effects occurring in more than 1 in 10 patients include nausea, headache, leucopenia, upper respiratory tract infections, diarrhea, vomiting, and nasopharyngitis. Serious adverse effects center primarily on liver function abnormalities and pneumonia.

Mandatory Liver Monitoring and Stopping Rules 

Before starting treatment, liver function tests including hepatic aminotransferases and total bilirubin must be performed.

During treatment, liver function must be monitored every 2 weeks for the first 3 months, followed by every 4 weeks for the subsequent 3 months, with additional testing as clinically indicated thereafter.

Treatment must be stopped if alkaline phosphatase levels are more than twice the normal limit when the hepatic origin has been confirmed, or when there are clinical symptoms of VBDS such as jaundice or itching. If VBDS is suspected, treatment must be immediately and permanently stopped. These cessation criteria are in addition to stopping rules already included in the product information.

Ongoing Regulatory Review 

The EMA is also conducting a review of Tavneos prompted by questions regarding data integrity of the main study. Clinicians should adhere to the reinforced liver surveillance protocols while this review proceeds.