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Update - Tocilizumab and hepatotoxicity

Medicines Safety Update
Published

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.

Patient management

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:

For more information about reporting, visit www.tga.gov.au or contact the TGA's Pharmacovigilance and Special Access Branch ADR.Reports@tga.gov.au.

Disclaimer

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

This work is copyright. You may reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the TGA Copyright Officer, Therapeutic Goods Administration, PO Box 100, Woden ACT 2606 or emailed to .

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For correspondence or further information about Medicines Safety Update, contact the TGA's Pharmacovigilance and Special Access Branch at .

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

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