Metronidazole and Tinidazole

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 thanmetronidazole, allowing for less frequent dosing.

Metronidazole is active against

• All obligate anaerobic bacteria (it is inactive against facultative anaerobic and aerobic bacteria)

• Certain protozoan parasites (eg, Trichomonas vaginalis, Entamoeba histolytica, Giardia intestinalis [lamblia])

Metronidazole is used primarily for infections caused by obligate anaerobes, often with other antimicrobials. Metronidazole is the antibiotic of choice for bacterial vaginosis. It also has other clinical uses (see table Some Clinical Uses of Metronidazole).

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

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

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 ofmetronidazole during pregnancy; however, in some studies, cleft lip (with or without cleft palate) was reported in neonates of women who took metronidazole during the first trimester. Some experts advise avoiding metronidazole during the first 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 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. A disulfiram-like reaction (including flushing, headache, nausea, and vomiting) may occur if alcohol is ingested within 3 days of use.

Metronidazole can cause a metallic taste and dark urine.

Tinidazole may have a slightly lower incidence of gastrointestinal disturbance.

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.

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

1. Centers for Disease Control and Prevention (CDC): Sexually Transmitted Infections Treatment Guidelines (2021)