Overview

Proton pump inhibitors (PPI) are widely used for treatment of gastro-oesophageal reflux (GERD), Helicobacter pylori eradication, prophylaxis of gastrointestinal ulcer, as well as in patients who are taking non-steroidal anti-inflammatory drugs (NSAIDs).¹

Microscopic colitis is a chronic inflammatory colon disease presenting with persistent watery and non-bloody diarrhoea.² There are two (2) types of microscopic colitis, which are lymphocytic colitis and collagenous colitis. The cause of microscopic colitis is still unknown and the pathogenesis is not well understood. However, there are many factors suspected to cause microscopic colitis, including drug consumption. With the growing number of PPI use, the occurrence of microscopic colitis associated with PPIs has been observed consistently.

Background

NPRA has received information from the European Medicines Agency (EMA) regarding Pharmacovigilance Risk Assessment Committee’s (PRAC) recommendation to all product registration holders of pantoprazole, to update the package insert with risk of microscopic colitis.⁴ In PRAC’s safety review, it was found that microscopic colitis has been included in the label of other PPIs and is likely a class effect.

In Malaysia, there are currently 72 registered PPIs-containing products containing pantoprazole, omeprazole, lansoprazole, esomeprazole, rabeprazole, dexlansoprazole or vonoprazan.¹

Adverse Drug Reaction (ADR) Reports:

To date, NPRA has not received any report regarding microscopic colitis associated with the use of PPIs.⁵ However, there were 30 reports associated with diarrhoea received.

Advice for Healthcare Professionals

• Be alert on the risk of microscopic colitis associated with the use of proton pump inhibitors. Diarrhoea is one of the symptoms of microscopic colitis.
• Avoid unnecessary treatment with PPIs to reduce the possible risk of microscopic colitis and discontinue the therapy where appropriate.
• Report all adverse events suspected to be related to PPIs to NPRA.

NPRA has completed a review of this safety issue and a directive [Ruj. Kami: (7) dlm. BPFK/PPP/07/25 Jld. 4] has been issued for registration holders of PPI-containing products to update the local package inserts and consumer medication information leaflet (Risalah Maklumat Ubat untuk Pengguna) to reflect this safety information.

References:

1. The NPRA QUEST 3+ database [Accessed: February 2020].
2. Ernest H. Law et al. (2016). Association between proton pump inhibitors and microscopic colitis: Implications for practice and future research. Annals of Pharmacotherapy.
3. Bonderup et al. (2018). Significant association between the use of different proton pump inhibitors and microscopic colitis: a nationwide Danish case-control study. Aliment Pharmacol Ther. 2018; 1-8.
4. European Medicines Agency (2019). PRAC recommendations on signals: Adopted at the 13-16 May 2019 meeting. Pantoprazole and colitis microscopic. EMA/PRAC/265212/2019.
5. The Malaysian Adverse Drug Reaction database, NPRA [Accessed: February 2020].

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.