Tocilizumab

Rare risk of hepatic injury

Ireland. The HPRA has announced that serious cases of drug-induced liver injury, (such as acute liver failure, hepatitis and jaundice and cases requiring liver transplantation) have been observed in patients treated with tocilizumab (RoActemra®).

Tocilizumab is an interleukin inhibitor indicated for the treatment of rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis and chimeric antigen receptor T-cell-induced severe cytokine release syndrome.

A recent review of data from clinical trials, noninterventional studies, spontaneous reports, and the published literature identified eight cases of tocilizumabrelated drug-induced liver injury worldwide. Two cases of acute liver failure required liver transplantation.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be monitored in patients. Also, patients should be advised to immediately seek medical help if they experience signs and symptoms of hepatic injury. Health-care professionals should refer to the guidance in the approved product information.

Reference : Drug Safety Newsletter, HPRA, August 2019 (www.hpra.ie)

Risk of hepatotoxicity

Australia. The Therapeutic Goods Administration (TGA) has announced that serious drug-induced liver injuries, including acute liver failure, hepatitis and jaundice, have been observed with the administration of tocilizumab (Actemra®).

Indications of tocilizumab include treatment of rheumatoid arthritis, giant cell arteritis in adults, and polyarticular juvenile idiopathic arthritis in patients of two years of age and older. Tocilizumab is known to cause transient or intermittent mild to moderate elevation of hepatic transaminases.

The TGA advises patients treated with tocilizumab to be closely monitored for liver adverse events and advised to seek immediate medical advice if they have signs or symptoms of hepatotoxicity such as jaundice, dark urine, itch, loss of appetite, nausea or vomiting.

The current Product Information does not recommend treatment in patients with elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST). The TGA is reviewing the data on hepatotoxicity with tocilizumab and may recommend changes to the Product Information.

Reference: Medicines Safety Update, TGA, 11 July 2019 (tga.gov.au)

United Kingdom. The MHRA has announced that serious liver injury has been reported in patients treated with tocilizumab (RoActemra®), with an onset ranging from two weeks to more than five years after initiation. Liver injury includes acute liver failure and hepatitis, and some cases required liver transplantation.

A recent EU cumulative review found that treatment was associated with severe liver injury. The review of data from clinical trials, noninterventional studies, spontaneous reports, and the published literature identified eight cases of tocilizumabrelated drug-induced liver injury worldwide.

ALT and AST levels should be measured before starting treatment with tocilizumab and monitored every four to eight weeks for the first six months of treatment followed by every 12 weeks thereafter.

Reference: Drug Safety Update, MHRA, 17 July 2019 (www.gov.uk/mhra)