Overview

In Malaysia, oseltamivir is generally indicated for treatment and post-exposure prophylaxis of influenza infection for adults and children.¹ Oseltamivir is an antiviral drug that acts against neuraminidase, which is the targeted catalytic site to prevent virus replication.²

Currently, there are 10 registered products containing oseltamivir (available as capsule and oral suspension).

Background of the safety issue

The National Regulatory Pharmaceutical Agency (NPRA) has received information from the product innovator of oseltamivir regarding thrombocytopenia associated with the use of oseltamivir. The product innovator had notified a review on this safety issue that was conducted by Swissmedic, the national regulatory agency of Switzerland. The review was initiated from the identification of four (4) case reports of thrombocytopenia following administration of oseltamivir in the Swiss national adverse drug reaction database. Following the review, product registration holder of oseltamivir was required to update the product information with this risk.

The European Medicines Agency (EMA) had also required a product information update on oseltamivir-containing products with the risk of thrombocytopenia in 2011. This request was made based on the Periodic Safety Update Report (PSUR) assessment for oseltamivir products, where there had been reports of thrombocytopenia in adults and children aged above 6 months old receiving oseltamivir.³

Further review by NPRA showed that thrombocytopenia has been reported in a clinical trial⁴ and a total of 61 cases has been reported globally in the World Health Organization (WHO) database.⁵

Adverse Drug Reaction (ADR) Reports

To date, the NPRA has received a total of 167 reports with 280 adverse events suspected to be related to oseltamivir containing products.⁶ However, no ADR related to thrombocytopenia following the use of oseltamivir has been reported locally.

Advice for Healthcare Professionals:

• Be alert on the risk of thrombocytopenia associated with the use of oseltamivir.
• Monitor platelet counts for patients taking oseltamivir.
• Advise patients to inform their doctor immediately if they experience symptoms of thrombocytopenia.
• Report all suspected adverse events associated with oseltamivir-containing products to the NPRA.

NPRA has completed a review of this safety issue and a directive [Ruj. Kami: NPRA.600-1/9/13 (16)] has been issued for registration holders of oseltamivir products to update the local package inserts and consumer medication information leaflet (Risalah Maklumat Ubat untuk Pengguna) to reflect this safety information.

References:

1. National Pharmaceutical Regulatory Agency. Malaysian Product Registration Database (Quest 3+). Oseltamivir local package insert [Internet]. Last revision date: 2020 Sept [Cited 2020 Aug 28]. Available from http://www.npra.gov.my
2. Tambunan U.S.F, Rachmania R.A, Parikesit A.A. In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1. The Journal of Biomedical Research [Internet] 2015 [Cited 10 November 2020] 29(2):150-159. Available from http://www.doi.org/10.7555/JBR.29.20130024
3. European Medicines Agency (EMA).Tamiflu-Procedural steps taken and scientific information after the authorisation [Internet]. 2009 December 1 [Cited 2020 November 10]. EMA/211836/2020
4. Raisch DW, Straight TM, Holodniy M. Thrombocytopenia from combination treatment with oseltamivir and probenecid: case report, MedWatch data summary, and review of the literature. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2009 Aug [Cited on 2020 November 10];29(8):988-92. Available from http://www.doi.org/10.1592/phco.29.8.988 
5. VigiLyze, World Health Organisation Uppsala Monitoring Centre [Internet]. 2020 [Cited 2020 Aug 28]. Available from https://vigilyze.who-umc.org/ 
6. National Pharmaceutical Regulatory Agency. The Malaysian National ADR Database [Internet]. 2020 [Cited 2020 Aug 28]. Available from https://www.npra.gov.my

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.