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Metronidazole / Mebendazole Drug interaction


MetroNIDAZOLE (Systemic) / Mebendazole
Risk Rating
X: Avoid combination
Summary
Mebendazole may enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). Particularly the risk for Stevens-Johnson syndrome or toxic epidermal necrolysis may be increased.
Severity Major
Reliability Fair
Management
Avoid the combination of mebendazole and metronidazole due to the potential increased risk of Stevens-Johnson syndrome or toxic epidermal necrolysis.
Discussion
A case control study of 46 patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) and matched controls (2 per case) reported greater use of combined mebendazole and metronidazole among cases than controls (76% vs 25%), with a corresponding odds ratio (OR) (95% confidence interval) associated with the use of the combination of 9.5 (3.9 to 23.9).1 Use of either drug alone was not associated with an increased risk of SJS/TEN, although reports of SJS/TEN with each drug alone have been reported previously.2,3,4Metronidazole doses of 2,000 mg per day or greater were associated with an increased occurrence of SJS/TEN (OR 18.9 [3.6 to 112.8]) compared with doses of 1,000 mg or less per day. The opposite dose relationship was observed for mebendazole, with higher doses (2,000 mg per day or greater) associated with a lower odds for SJS/TEN (OR 0.1 [0.03 to 0.6]) compared with lower doses (1,000 mg per day or less). The authors of the report suspected that the inverse dose relationship was due to the use of lower mebendazole doses in combination with higher dose metronidazole.1



Due to this report, the mebendazole Canadian product monograph recommends avoidance of the combination of mebendazole and metronidazole.5



Whether the metronidazole (or mebendazole) dose or the combined use of metronidazole and mebendazole is primarily responsible for the cases of SJS/TEN evaluated in this study is uncertain, as is the precise mechanism by which dose or a drug interaction would cause SJS/TEN.

Footnotes

1. Chen KT, Twu SJ, Chang HJ, Lin RS. Outbreak of Stevens-Johnson syndrome/toxic epidermal necrolysis associated with mebendazole and metronidazole use among Filipino laborers in Taiwan. Am J Public Health. 2003;93(3):489-492. [PubMed 12604501]
2. Mazumdar G, Shome K. Stevens-Johnson syndrome following use of metronidazole in a dental patient. Indian J Pharmacol. 2014;46(1):121-122. [PubMed 24550598]
3. Piskin G, Mekkes JR. Stevens-Johnson syndrome from metronidazole. Contact Dermatitis. 2006;55(3):192-193. [16918620]
4. Ajonuma LC, Chika LC. Outbreak of Stevens-Johnson syndrome among Filipino overseas contract workers using mebendazole for helminthiasis prophylaxis. Trop Doct. 2000;30(1):57. [PubMed 10842543]

Lexicomp Interaction Android app, Feb 15, 2019