Overview

Sertraline is an antidepressant that belongs to the group of Selective Serotonin Reuptake Inhibitors (SSRIs). In Malaysia, the Drug Control Authority has currently approved 12 sertraline-containing products for the treatment of depression, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, and social anxiety disorder.¹ While SSRIs are often associated with gastrointestinal adverse effects, diarrhoea is more commonly reported with sertraline as compared to other SSRIs.²

Microscopic colitis is a type of inflammatory bowel disease (IBD) characterised by normal colonic mucosa appearance but presented with a distinctive histological inflammation when viewed under the microscope.^3-5 Chronic, watery, non-bloody diarrhoea is the most common symptom of microscopic colitis. Other symptoms, which may considerably impair the patient’s quality of life, include abdominal pain, weight loss, dehydration, fatigue, and faecal incontinence. Rarely, microscopic colitis may lead to serious complications including colon ulcers or perforation. ^4-5

Background of the Safety Issue

In June 2020, the National Pharmaceutical Regulatory Agency (NPRA) through its global safety signal monitoring activity learned from the European Medicines Agency (EMA) about the risk of microscopic colitis associated with the use of sertraline.⁶

Based on the evidence from the literature and spontaneous reports from the Eudravigilance database, EMA had requested product registration holders of all sertraline-containing products to include microscopic colitis as one of the side effects.⁶

The exact mechanism of how sertraline induces microscopic colitis remains unknown. According to published literature, the likelihood of association derives from the temporal relationship between treatment initiation and symptom onset, as well as the disappearance of symptoms following the withdrawal of the drug.²

Adverse Drug Reaction (ADR) Reports⁷

To date, NPRA has received 322 reports with 686 adverse events suspected to be related to sertraline. From these reports, there were no local reports of microscopic colitis. However, there were 16 reports of diarrhoea.

Advice for Healthcare Professionals:

• Educate patients on the signs and symptoms of microscopic colitis during the initiation of sertraline therapy.
• Consider the possibility of microscopic colitis in patients on sertraline therapy who present with severe or prolonged diarrhoea.
• Refer patients to the gastroenterology team for further investigation to rule in microscopic colitis if necessary.
• When microscopic colitis is confirmed, consider stopping treatment with sertraline and replace with an alternative treatment.
• Report all suspected adverse events associated with sertraline-containing products to the NPRA.

NPRA has completed a review of this safety issue and a directive [Ruj. Kami: NPRA.600-1/9/13 (14) Jld.1] has been issued for all registration holders of products containing setraline to update the local package inserts and consumer medication information leaflets (Risalah Maklumat Ubat untuk Pengguna) to reflect this safety information.

References:

1. National Pharmaceutical Regulatory Agency (NPRA). QUEST3+ Product Search [Internet]. 2022 [cited 2022 Jul 14]. Available from: https://www.npra.gov.my
2. Hernández-Huerta D, Mesonero-Gismero F. Antidepressants and its relationship with microscopic colitis. Actas Esp Psiquiatr.[Internet]. 2018 [cited 2022 Jan 14];46(5):200-4. Epub Available from: https://www.actaspsiquiatria.es/repositorio//20/115/ENG/20-115-ENG-200-4-734558.pdf
3. Wenzl H. Diarrhea in Chronic Inflammatory Bowel Diseases. Gastroenterology Clinics of North America. 2012; 41(3):651-675. Available from: https://doi.org/10.1016/j.gtc.2012.06.006
4. United States National Institute of Diabetes and Digestive and Kidney Diseases (NIDKK). Microscopic Colitis [Internet]. 2022 [cited 2022 Jul 14]. Available from: https://www.niddk.nih.gov/health-information/digestive-diseases/microscopic-colitis
5. Tysk C, Bohr J, Nyhlin N, Wickbom A, Eriksson S. Diagnosis and management of microscopic colitis. World Journal of Gastroenterology. 2008;14(48):7280. Available from: https://doi.org/ 3748/wjg.14.7280
6. European Medicines Agency (EMA). PRAC recommendations on signals: Adopted at the 11-14 May 2020 PRAC meeting [Internet]. 2021 May 31 [cited 2021 Jun 21]. Available from: https://www.ema.europa.eu/en/documents/prac-
7. National Pharmaceutical Regulatory Agency (NPRA). The Malaysian National ADR Database (QUEST) [Internet]. 2021 [cited 2022 Jul 14]. Available from: https://www.npra.gov.my (access restricted)

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, NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.

Written by: Noor'ain Shamsuddin
Reviewed/Edited by: Choo Sim Mei, Lim Sze Gee, Dr Azuana Ramli