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Metronidazole – systemic use

Classification: A

Drug products: Flagyl, Flagyl®, Metronidazol Actavis, Metronidazol Baxter, Metronidazol EQL Pharma, Metronidazole Bioren, Metronidazole Braun, Metronidazole Tablets BP

ATC code: J01XD01, P01AB01


A systematic review found the resistance of Helicobacter pylori to metronidazol to be higher in women. A small pharmacokinetic study showed lower exposure and higher clearance of metronidazole in women after adjusting for body weight. These pharmacokinetic differences are not considered clinically important.

Additional information

Pharmacokinetics and dosing

In an open, single-dose, two-sequence, crossover randomized trial (12 men, 12 women), bioequivalence of two different formulations of metronidazole (250 mg) and sex differences in pharmacokinetics were studied. Bioequivalence analysis showed that the formulations were similar. However, differences in pharmacokinetic parameters were observed between men and women. Following dose-adjustment for body weight, AUC for metronidazole was lower (12%) and clearance was higher in women. In accordance to these findings, metronidazole half-life was shorter among women. Volume of distribution was higher in men. However, according to the authors, these findings are most likely clinically irrelevant and no dosage adjustment based on sex are not considered necessary [1].


No studies with a clinically relevant sex analysis regarding effect of metronidazole have been found.

Adverse events

Safety of metronidazole for Clostridioides difficile infection was analysed retrospectively in a Japanese study using electronic chart data. Nausea was more frequent in women than in men (13.6% vs 1.1%) treated with metronidazole [2].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

Several studies report differences in Helicobacter pylori antibiotic resistance between men and women. A systematic review of 31 studies, published worldwide 2006-2009, found that overall, primary metronidazole resistance was more common among women than men (31.4% vs. 21.1%). Also, metronidazole resistance rate varied widely between different populations. High resistance was reported from Denmark and Korea while low resistance was observed in Sweden, the Netherlands and Japan [3].

Another study based on US-data from clinical trials between 1993 and 1999 (6087 isolates, distribution male vs. female samples unknown), described higher frequency of primary metronidazole resistant Helicobacter pylori among women than men (63% vs. 35% or 34.7% vs. 22.6%, depending on test method). The authors hypothesize that this finding is due to the use of metronidazole to treat gynecologic infections. For both men and women metronidazole resistance was more common before the age of 70 [4].


Updated: 2021-12-21

Date of litterature search: 2021-11-18


  1. Carcas AJ, Guerra P, Frias J, Soto A, Fernandez-Aijón A, Montuenga C et al. Gender differences in the disposition of metronidazole. Int J Clin Pharmacol Ther. 2001;39:213-8. PubMed
  2. Misawa K, Iketani O, Enoki Y, Taguchi K, Uno S, Uwamino Y et al. Retrospective study of the efficacy and safety of metronidazole and vancomycin for Clostridioides difficile infection. J Infect Chemother. 2021;27(10):1407-1412. PubMed
  3. De Francesco V, Giorgio F, Hassan C, Manes G, Vannella L, Panella C et al. Worldwide H pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis. 2010;19:409-14. PubMed
  4. Osato MS, Reddy R, Reddy SG, Penland RL, Malaty HM, Graham DY. Pattern of primary resistance of Helicobacter pylori to metronidazole or clarithromycin in the United States. Arch Intern Med. 2001;161:1217-20. PubMed
  5. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2020 [cited 2021-03-10.] länk
  6. Conise (INSIKT). Kalmar: eHälsomyndigheten. 2018 [cited 2021-11-18.] länk

Authors: Linnéa Karlsson Lind

Reviewed by: Diana Rydberg, Carl-Olav Stiller

Approved by: Karin Schenck-Gustafsson