Products
Metronidazole is commercially available in various dosage forms for systemic and topical therapy. This article refers to the film-coated tablets (Flagyl and generic). The drug has been approved in many countries since 1960.
Structure and properties
Metronidazole (C6H9N3O3, Mr = 171.2 g/mol) is a derivative of imidazole substituted with a nitro group, a methyl group and ethanol. It exists as a white to yellowish crystalline powder with a bitter taste that is sensitive to light and sparingly soluble in water. The active ingredient was developed at Rhône-Poulenc starting from azomycin, a natural product isolated from a -species in the 1950s.
Effects
Metronidazole (ATC J01XD01) has both bactericidal properties against anaerobic bacteria and antiparasitic effects against protozoa (single-celled organisms). It is a prodrug that is metabolized under anaerobic conditions in the cell to nitroso radicals that attack DNA. This results in strand breaks, inhibition of DNA synthesis and cell death. Metronidazole distributes well to tissues and has a half-life of 8 hours (6 to 10 hours).
Indications
- For the treatment of infections with susceptible anaerobic bacteria.
- Intestinal and hepatic amebiasis (, parasite).
- Trichomoniasis (, parasite).
- Bacterial vaginosis, Gardnerella vaginalis infections (, bacterium).
- Lambliasis (giardiasis, , parasite).
Dosage
According to the professional information. Tablets are taken between one to four times a day for several days. Short therapy may be given for some infections. A high dose is given once or twice. The German information leaflet recommends taking the tablets during or after meals. Metronidazole is not intended for continuous therapy. As a rule, the duration of therapy should not exceed 10 days. Repeat treatment should be as infrequent as possible. The duration of treatment has been limited because damage to human germ cells cannot be ruled out and mutagenic and carcinogenic effects have been observed in animal studies.
Contraindications
- Hypersensitivity
- Pregnancy
- Lactation
Full precautions can be found in the drug label.
Interactions
No alcohol should be drunk or ingested just before, during, or for at least one day after treatment because Antabuse effects may occur. These include flushing of the skin, nausea, vomiting, a rapid heartbeat, headache, abdominal cramps, and dizziness. The U.S. drug label even recommends a grace period of three days after discontinuation and additionally mentions that propylene glycol must also be avoided. Other drug interactions have been described with vitamin K antagonists, disulfiram, enzyme inducers, enzyme inhibitors, lithium, ciclosporin, 5-fluorouracil, and busulfan.
Adverse effects
Possible adverse effects, which are occasional to common, include:
- Nausea, upper abdominal pain, vomiting, diarrhea, loss of appetite, glossitis, oral mucositis.
- Taste disturbances: Metallic taste, bitter regurgitation.
- Sensory disturbances (paresthesias).
- Headache, dizziness, depression insomnia, weakness, gait disturbances, confusion.
- Skin rash, itching, flushing.
Metronidazole can darken the urine. Professionals should communicate this to patients so that there is no uncertainty.
