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 . 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.
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
All obligate anaerobic bacteria Overview of Anaerobic Bacteria Bacteria can be classified by their need and tolerance for oxygen: Facultative: Grow aerobically or anaerobically in the presence or absence of oxygen Microaerophilic: Require a low oxygen concentration... read more (it is inactive against facultative anaerobic and aerobic bacteria)
Certain protozoan parasites (eg, Trichomonas vaginalis Trichomoniasis Trichomoniasis is infection of the vagina or male genital tract with Trichomonas vaginalis. It can be asymptomatic or cause urethritis, vaginitis, or occasionally cystitis, epididymitis, or... read more , Entamoeba histolytica Amebiasis Amebiasis is infection with Entamoeba histolytica. It is acquired by fecal-oral transmission. Infection is commonly asymptomatic, but symptoms ranging from mild diarrhea to severe dysentery... read more , Giardia intestinalis Giardiasis Giardiasis is infection with the flagellated protozoan Giardia duodenalis (G. lamblia, G. intestinalis). Infection can be asymptomatic or cause symptoms ranging from intermittent flatulence... read more [lamblia])
Metronidazole is used primarily for infections caused by obligate anaerobes, often with other antimicrobials. Metronidazole is the drug of choice for bacterial vaginosis Bacterial Vaginosis (BV) Bacterial vaginosis is vaginitis due to a complex alteration of vaginal flora in which lactobacilli decrease and anaerobic pathogens overgrow. Symptoms include a gray, thin, fishy-smelling vaginal... read more . The drug has other clinical uses (see table Some Clinical Uses of Metronidazole Some Clinical Uses of Metronidazole Metronidazole is a bactericidal antibiotic. It enters bacterial cell walls and disrupts DNA and inhibits DNA synthesis in certain microorganisms. Tinidazole is a related nitroimidazole with... read more ).
Tinidazole is used primarily for the protozoan parasites mentioned above. It is not used for systemic anaerobic bacterial infections.
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) 2015 sexually transmitted diseases 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.
Adverse Effects of Metronidazole and Tinidazole
Adverse effects of metronidazole and tinidazole include
Central nervous system effects and peripheral neuropathy
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.