Tocilizumab and hepatotoxicity

Health professionals are advised that serious drug-induced liver injury, including acute liver failure, hepatitis and jaundice, have been observed with the administration of tocilizumab. The frequency of serious hepatotoxicity is considered rare, but in some cases treatment has required liver transplant.

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.

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.

The current Product Information (PI) for tocilizumab does not recommend treatment in patients with elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above five times the upper limit of normal (ULN). Caution should continue to be exercised when considering initiation of tocilizumab treatment in patients with ALT or AST above 1.5 times ULN.

For recommended dose modifications (reduction, interruption or discontinuation) of tocilizumab due to liver enzyme abnormalities, refer to the PI.

Tocilizumab is known to cause transient or intermittent mild to moderate elevation of hepatic transaminases.

The TGA is currently reviewing the data on the nature and incidence of hepatotoxicity with tocilizumab, and may recommend changes to the 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:

• online at www.tga.gov.au
• by fax to 02 6232 8392
• by email to ADR.Reports@tga.gov.au

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 tga.copyright@tga.gov.au.

For the latest safety information from the TGA, subscribe to the TGA Safety Information email list via the TGA website.

For correspondence or further information about Medicines Safety Update, contact the TGA's Pharmacovigilance and Special Access Branch at ADR.Reports@tga.gov.au.

Medicines Safety Update is written by staff from the Pharmacovigilance and Special Access Branch.

Acting Editor: Dr Grant Pegg

Deputy Editor: Mr Michael Pittman

Contributors include: Dr Richard Hill