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Update - Tocilizumab and hepatotoxicity
Medicines Safety Update
Following the July 2019 MSU article regarding tocilizumab and hepatotoxicity, the Product Information (PI) for tocilizumab has been updated to include more information about this potential safety issue.
Tocilizumab, which is marketed in Australia under the brand name Actemra, is indicated for treatment of:
- rheumatoid arthritis
- giant cell arteritis in adults
- polyarticular juvenile idiopathic arthritis in patients 2 years of age and older
- systemic juvenile idiopathic arthritis in patients 2 years of age and older
- chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in adults and paediatric patients 2 years of age and older.
Cases of serious hepatic injury
A comprehensive assessment of reports of serious hepatic injury associated with tocilizumab use has been performed across all available clinical and post-marketing data sources. The sponsor of Actemra, Roche, has identified eight cases of tocilizumab-related moderate to severe drug-induced liver injury, including acute liver failure, hepatitis and jaundice. These events occurred between two weeks to more than five years after initiation of tocilizumab, with median latency of 98 days. In these eight cases, two cases of acute liver failure required liver transplantation.
These events are considered rare and the benefit-risk profile of tocilizumab in the approved indications remains favourable.
Health professionals are reminded that tocilizumab is known to cause transient mild to moderate elevation of hepatic transaminases, with increased frequency when used in combination with other potentially hepatotoxic drugs (such as methotrexate).
Patients treated with tocilizumab should 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. Patients presenting with signs or symptoms of hepatotoxicity should be promptly investigated.
It is not recommended to initiate tocilizumab treatment in patients with elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 1.5 times the upper limit of normal (ULN), except in cases of cytokine release syndrome. In patients who develop elevated ALT or AST greater than five times ULN, discontinue tocilizumab.
Health professionals are advised to follow all guidance relating to liver enzyme abnormalities, including dose modification and tocilizumab discontinuation, contained in the updated PI.
What to report? You don't need to be certain, just suspicious!
The TGA encourages the reporting of all suspected adverse reactions to medicines, including vaccines, over-the-counter medicines, herbal, traditional or alternative remedies.
We particularly request reports of:
- all suspected reactions to new medicines
- all suspected medicines interactions
- suspected reactions causing death, admission to hospital or prolongation of hospitalisation, increased investigations or treatment, or birth defects.
Reports may be submitted:
Medicines Safety Update is aimed at health professionals. It is intended to provide practical information to health professionals on medicine safety, including emerging safety issues. The information in Medicines Safety Update is necessarily general and is not intended to be a substitute for a health professional's judgment in each case, taking into account the individual circumstances of their patients. Reasonable care has been taken to ensure that the information is accurate and complete at the time of publication. The Australian Government gives no warranty that the information in this document is accurate or complete, and shall not be liable for any loss whatsoever due to negligence or otherwise arising from the use of or reliance on this document.
© Commonwealth of Australia 2019
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Medicines Safety Update is written by staff from the Pharmacovigilance and Special Access Branch.
Acting Editor: Dr Grant Pegg
Deputy Editor: Mr Michael Pittman
Contributor: Dr Richard Hill