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Metronidazole and Tinidazole

By

Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Reviewed/Revised May 2022
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Topic Resources

Metronidazole is a bactericidal antibiotic Overview of Antibacterial Drugs Antibacterial drugs are derived from bacteria or molds or are synthesized de novo. Technically, “antibiotic” refers only to antimicrobials derived from bacteria or molds but is often (including... read more Overview of Antibacterial Drugs . It enters bacterial cell walls and disrupts DNA and inhibits DNA synthesis in certain microorganisms. Tinidazole is a related nitroimidazole with similar mechanism of action but more limited clinical use.

Pharmacokinetics

Oral metronidazole is absorbed well. It is usually given IV only if patients cannot be treated orally. It is distributed widely in body fluids and penetrates into cerebrospinal fluid, resulting in high concentrations.

Metronidazole is metabolized presumably in the liver and excreted mainly in urine, but elimination is not decreased in patients with renal insufficiency. However, because metronidazole metabolites may accumulate in patients with end-stage renal disease, these patients should be monitored for metronidazole-associated adverse effects such as central nervous system effects, including headaches, convulsions, and peripheral neuropathy (mainly numbness or paresthesias in an extremity).

Tinidazole has a slightly longer half-life than metronidazole, allowing for less frequent dosing.

Indications for Metronidazole and Tinidazole

Metronidazole is active against

Tinidazole is used primarily for the protozoan parasites mentioned above. It is not used for systemic anaerobic bacterial infections.

Table

Some Clinical Uses of Metronidazole

Indication

Comments

Often used with other antimicrobials

Drug of choice

Septicemia

Prophylaxis before intestinal surgery

No longer recommended as a first-line drug

Should be considered only for mild cases when vancomycin or fidaxomicin are unavailable or for severe systemic cases given in combination with vancomycin

For treatment and prevention of relapses

Used with other drugs

Topical or oral use

Contraindications to Metronidazole and Tinidazole

Metronidazole and tinidazole are contraindicated in patients who have had an allergic reaction to it.

Use During Pregnancy and Breastfeeding

Reproduction studies with metronidazole in some animal species showed increased risk of carcinogenic activity. No adequate and well-controlled studies have been done in pregnant women. Most human studies have not shown increased risk of cancer, birth defects, or other fetal adverse effects after use of metronidazole during pregnancy; however, in some studies, cleft lip (with or without cleft palate) was reported in neonates of women who took metronidazole during the 1st trimester. Some experts advise avoiding metronidazole during the 1st trimester, although the Centers for Disease Control and Prevention's (CDC) 2021 sexually transmitted infections treatment guidelines indicate that a single 2-g dose can be used at any stage of pregnancy to treat trichomoniasis.

Metronidazole enters breast milk; use during breastfeeding is not recommended.

There are limited data on use of tinidazole during pregnancy, but because animal studies suggest moderate risk, tinidazole is avoided during pregnancy. Breastfeeding should be deferred for 72 hours after a single 2-g oral dose of tinidazole.

Adverse Effects of Metronidazole and Tinidazole

Adverse effects of metronidazole and tinidazole include

  • Gastrointestinal disturbances

  • Central nervous system effects and peripheral neuropathy

  • Disulfiram-like reaction

Nausea, vomiting, headache, seizures, syncope, other central nervous system effects, and peripheral neuropathy can occur; rash, fever, and reversible neutropenia have been reported. Metronidazole can cause a metallic taste and dark urine. A disulfiram-like reaction (including flushing, headache, nausea, and vomiting) may occur if alcohol is ingested within 7 days of use.

Tinidazole may have a slightly lower incidence of gastrointestinal disturbance.

Dosing Considerations for Metronidazole and Tinidazole

Metronidazole and tinidazole doses are not decreased in patients with renal failure. Metronidazole doses are usually decreased 50% in patients with significant liver disease; tinidazole has not been studied in liver disease and should be used with caution if at all.

Metronidazole and tinidazole inhibit metabolism of warfarin and may increase its anticoagulant effect.

More Information

The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

Drugs Mentioned In This Article

Drug Name Select Trade
Flagyl, Flagyl ER, Flagyl RTU, LIKMEZ, MetroCream, MetroGel, MetroGel Vaginal, MetroLotion, Noritate, NUVESSA, Nydamax, Rosadan, Rozex, Vandazole, Vitazol
Tindamax
Antabuse
Coumadin, Jantoven
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NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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