Ceftriaxone and risk of hepatitis and encephalopathy

Health professionals are advised that the Product Information (PI) for ceftriaxone has been updated to include a warning about encephalopathy, particularly in older patients with underlying renal impairment or central nervous system disorders. Hepatitis has also been listed as a potential adverse event of ceftriaxone, along with encephalopathy.

Ceftriaxone (also known as ceftriaxone sodium) is a broad-spectrum cephalosporin antibiotic used in adults and children. It is approved for the treatment of pneumonia, skin infections, urinary tract infection, gonorrhoea, septicaemia, meningitis, bone and joint infections. It is also used for surgical prophylaxis.

Warnings about encephalopathy and hepatitis have been added to the ceftriaxone PI based on evidence published in the literature and from post-market adverse event data in Australia and internationally.^[1],[2]

The following warning has been added to section 4.4 of the PI 'Encephalopathy has been reported with the use of ceftriaxone, particularly in elderly patients with severe renal impairment or central nervous system disorders. If ceftriaxone-associated encephalopathy is suspected (e.g. decreased level of consciousness, altered mental state, myoclonus, convulsions), discontinuation of ceftriaxone should be considered.'

'Hepatitis and hepatic cholestatic (frequency unknown)' and 'encephalopathy (rare)' have been added to section 4.8 of the PI as potential adverse effects.

Adverse events reported to the TGA

To 16 November 2021, we have received 38 reports of hepatitis, 10 of cholestatic hepatitis, 3 of hepatomegaly and one of hepatocellular injury, all suspected to be related to ceftriaxone.

We have also received 3 reports of encephalopathy for ceftriaxone. Two of these cases are described in a study reviewing case reports of patients with cephalosporin-related neurotoxicity in Western Australia.^[1]

These reports are included in our Database of Adverse Event Notifications (DAEN).

Information for health professionals

These adverse events can have serious consequences for patients, and it is important that prescribers are aware of the risks.

Encephalopathy has been reported particularly in the elderly with severe renal impairment or central nervous system disorders. If you suspect encephalopathy, consider stopping the medicine.

See the latest PI documents for ceftriaxone products for further information.

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 (look for the Black Triangle in PI and CMI documents - this symbol identifies medicines that are new or being used differently)
• 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 2021

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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.

Editor: Dr Catherine Brogan

Deputy Editor: Mr Michael Pittman

Contributor: Ms Jovi van der Kallen and Ms Rebecca Page