This information is an update to the NPRA Safety Alerts published on 31 December 2021.

Overview

Clindamycin is a lincosamide antibiotic indicated for the treatment of various infections caused by susceptible anaerobic bacteria, susceptible strains of gram-positive aerobic bacteria such as streptococci, staphylococci and pneumococci, and susceptible strains of Chlamydia trachomatis.¹ In Malaysia, there are currently nine (9) registered products containing clindamycin for systemic use (oral and injectable preparations).²

Background of Safety Issue

The National Pharmaceutical Regulatory Agency (NPRA) received information from the European Medicines Agency (EMA) on the risk of acute renal failure associated with the systemic use of clindamycin.³

Following the review on data from the European pharmacovigilance database (EudraVigilance), published literature, and data submitted by the product registration holder, EMA concluded that there is a potential link between clindamycin-containing medicinal products for systemic use and the risk of acute renal failure.³ It is suggested that clindamycin-induced renal injury may be linked to the precipitation of high urine concentrations of clindamycin in the renal tubule that may cause tubular obstruction and thus result in direct tubular toxicity.^4-5

Similar regulatory actions have been taken by regulatory authorities in reference countries, including the United States, Canada, United Kingdom, Switzerland, and Japan.^6-12

Adverse Drug Reaction (ADR) Reports¹³

To date, the NPRA had received a total of 325 reports with 486 adverse events suspected to be related to clindamycin-containing products for systemic use. Of these, the number of reported events of acute kidney injury remained constant at two (2).

Advice for Health Care Professionals

• Be aware of the potential risk of acute kidney injury when prescribing clindamycin.
• Educate patients on the sign and symptoms of acute kidney injury such as decreased urine output, angioedema, dyspnoea, or nausea.
• Consider monitoring of renal function in patients receiving prolonged therapy, suffering from pre-existing renal dysfunction or taking concomitant nephrotoxic drugs.
• Please report all suspected adverse events associated with clindamycin to the NPRA.

NPRA had completed a review of this safety issue and a directive [Ruj. Kami: NPRA.600-1/9/13 (26) Jld.1] had been issued for all registration holders of products containing clindamycin for systemic use (oral and injectable preparations) 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). The Malaysian Product Registration Database (QUEST). DALACIN C CAPSULE (clindamycin) [Package Insert]. 2022 [cited 2022 Oct 25]. Available from: http://www.npra.gov.my (access restricted).
2. National Pharmaceutical Regulatory Agency (NPRA). QUEST3+ Product Search [Internet]. 2022 [cited 2022 Oct 25]. Available from: https://www.npra.gov.my
3. Pharmacovigilance Risk Assessment Committee (PRAC). PRAC recommendations on signals Adopted at the 3-6 May 2021 PRAC meeting: European Medicines Agency (EMA) [Internet]. 31 May 2021 [cited 2022 Oct 25]. Available from: https://www.ema.europa.eu/en/documents/prac-recommendation/prac-recommendations-signals-adopted-3-6-may-2021-prac-meeting_en.pdf
4. Sarwal A, Chiu C-Y, Feinstein A. Does Clindamycin Induce Acute Kidney Injury? Am J Med Sci [Internet]. 2020;359(5):303. Available from: https://doi.org/10.1016/j.amjms.2020.02.005
5. Xie H, Chen H, Hu Y, Xu S, He Q, Liu J, et al. Clindamycin-Induced Acute Kidney Injury: Large Biopsy Case Series. Am J Nephrol [Internet]. 2013;38(3):179–83. Available from: https://www.karger.com/DOI/10.1159/000354088
6. S. Food and Drug Administration. CLEOCIN HYDROCHLORIDE (clindamycin) [Package Insert]. Drug Safety-related Labeling Changes (SrLC). 2022 May [cited 2023 Mar 28] Available from: https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=279
7. Health Canada. DALACIN C 150 MG (clindamycin) [Package Insert]. Drug Product Database online query. 2022 Jan 10 [cited 2023 Mar 28] Available from: https://pdf.hres.ca/dpd_pm/00064285.PDF
8. Medicines and Healthcare Products Regulatory Agency (MHRA). DALACIN C CAPSULES 75 MG (clindamycin hydrochloride) [Package Insert]. Products. 2022 Apr 28 [cited 2023 Mar 28]. Available from: https://mhraproducts4853.blob.core.windows.net/docs/371845bac6ffbd430dc763a0c167a17f9de8b7c2
9. Agence nationale de sécurité du médicament et des produits de santé (ANSM). DALACINE 150 MG, GÉLULE (clindamycin) [Package Insert]. Research of pharmaceutical specialties. 2023 Jan 10 [cited 2023 Mar 28]. Available from: http://agence-prd.ansm.sante.fr/php/ecodex/frames.php?specid=64596029&typedoc=R&ref=R0398905.htm
10. Swedish Medical Products Agency. DALACIN 75 MG KAPSLAR, HÅRDA (clindamycin) [Package Insert]. Search drug facts 2022 May 22 [cited 2023 Mar 28]. Available from: https://docetp.mpa.se/LMF/Dalacin%20capsule,%20hard%20SmPC_09001bee807a0785.pdf
11. PRÄPARATNAME: DALACIN® C (clindamycin) [Package Insert]. Swissmedicinfo. 2022 Jan [cited 2023 Mar 28]. Available from: https://www.swissmedicinfo.ch/ViewMonographie
12. Pharmaceuticals and Medical Devices Agency (PMDA). ダラシンカプセル75MG／ダラシンカプセル150MG (clindamycin) [Package Insert]. Ethical drug information search. 2022 Jul [cited 2023 Mar 28]. Available from: https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/672212_6112001M1031_3_03
13. National Pharmaceutical Regulatory Agency (NPRA). The Malaysian National ADR Database (QUEST) [Internet]. 2022 [cited 2022 Oct 25]. 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, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.

Written by: Nafiza Mohd. Ismail
Reviewed/Edited by: Choo Sim Mei, Lim Sze Gee, Noor'ain Shamsuddin, Norleen Mohamed Ali