Overview

Isoniazid is an antibiotic used in the treatment of tuberculosis. It can be used alone (prevention) or in combination with other antituberculosis drugs (treatment). Pancreatitis is an inflammation of the pancreas and in general, it is caused by gallstones and alcohol use, but may also be triggered by drug reaction¹.

Background of Safety Issue

Health Canada had directed the product registration holders of isoniazid containing products to update their package insert with the risk of pancreatitis¹. The decision was made following triggers from the United States Food and Drug Administration (US FDA) and European Medicines Agency (EMA) package insert update for isoniazid to include this risk.

In Malaysia, there are currently six (6) products containing isoniazid registered with the Drug Control Authority (DCA)². A safety review on the risk of pancreatitis associated with the use of isoniazid was conducted and after considering all available evidence, NPRA has concluded that all products containing isoniazid must be updated with safety information on this risk.

Adverse Drug Reaction Reports³

The NPRA has received a total of 1,409 reports with 2,698 adverse events related to isoniazid containing products. The most reported adverse events were pruritus (290), followed by rash maculo-papular (260) and rash (140). To date, there is one (1) case of acute pancreatitis following the use of isoniazid-containing product reported to the NPRA.

Advice for Healthcare Professionals

• Patients on isoniazid therapy should be counselled on the signs and symptoms of pancreatitis. Advise patients to immediately seek medical attention at the hospital if the signs and symptoms start to appear.
• Consider rapid withdrawal of isoniazid and provide appropriate management of pancreatitis as soon as possible⁴.
• Please report all adverse events suspected to be related to the concomitant use of isoniazid to the NPRA.

A directive [Ruj. Kami: (27) dlm. BPFK/PPP/07/25 Jld. 2] has been issued by NPRA for updates to the local product packaging insert and consumer medication information leaflet (Risalah Maklumat Ubat untuk Pengguna) related to this safety issue. Please refer to the directive for more information.

References:

1. Health Canada (May 2018). Summary Safety Review – Isoniazid – Assessing the potential risk of inflammation of the pancreas (pancreatitis).
2. The NPRA QUEST 3+ database [Accessed: August 2018].
3. The Malaysian Adverse Drug Reaction database, NPRA [Accessed: August 2018]
4. Pancreatic Disorders & Therapy (2015). Drug-induced acute pancreatitis confirmed by positive re-challenge.

DISCLAIMER 
This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.