Metronidazole is listed as a possible carcinogen according to the World Health Organization (WHO) International Agency for Research on Cancer (IARC). A study in those with Crohns disease also found chromosomal abnormalities in circulating lymphocytes in people treated with metronidazole. Stevens–Johnson syndrome
Metronidazole alone rarely causes Stevens–Johnson syndrome, but is reported to occur at high rates when combined with mebendazole. Drug interactions
Alcohol
Consuming alcohol while taking metronidazole has been suspected in case reports to cause a disulfiram-like reaction with effects that can include nausea, vomiting, flushing of the skin, tachycardia, and shortness of breath. People are often advised not to drink alcohol during systemic metronidazole therapy and for at least 48 hours after completion of treatment. However, some studies call into question the mechanism of the interaction of alcohol and metronidazole,
and a possible central toxic serotonin reaction for the alcohol intolerance is suggested. Metronidazole is also generally thought to inhibit the liver metabolism of propylene glycol (found in some foods, medicines, and in many electronic cigarette e-liquids), thus propylene glycol may potentially have similar interaction effects with metronidazole. Other drug interactions
Metronidazole is a moderate CYP2C9 inhibitor. CYP2C9 is an enzyme of cytochrome P450 family. Therefore, metronidazole may interact with medications metabolized by this enzyme. Examples of such medications are lomitapide, warfarin, etc. Pharmacology
Mechanism of action
Metronidazole is of the nitroimidazole class. It inhibits nucleic acid synthesis by forming nitroso radicals, which disrupt the DNA of microbial cells.
In 2017, the IDSA generally recommended vancomycin and fidaxomicin over metronidazole. Vancomycin by mouth has been shown to be more effective in treating people with severe C. difficile colitis. E. histolytica
Entamoeba histolytica invasive amebiasis is treated with metronidazole for eradication, in combination with diloxanide to prevent recurrence. Although it is generally a standard treatment it is associated with some side effects. Preterm births
Metronidazole has also been used in women to prevent preterm birth associated with bacterial vaginosis, amongst other risk factors including the presence of cervicovaginal fetal fibronectin (fFN). Metronidazole was ineffective in preventing preterm delivery in high-risk pregnant women (selected by history and a positive fFN test) and, conversely, the incidence of preterm delivery was found to be higher in women treated with metronidazole. Hypoxic radiosensitizer
In addition to its anti-biotic properties, attempts were also made to use a possible radiation-sensitizing effect of metronidazole in the context of radiation therapy against hypoxic tumors. However, the neurotoxic side effects occurring at the required dosages have prevented the widespread use of metronidazole as an adjuvant agent in radiation therapy. However, other nitroimidazoles derived from metronidazole such as nimorazole with reduced electron affinity showed less serious neuronal side effects and have found their way into radio-onological practice for head and neck tumors in some countries. Perioral dermatitis
Canadian Family Physician has recommended topical metronidazole as a third-line treatment for the perioral dermatitis either along with or without oral tetracycline or oral erythromycin as first and second line treatment respectively.