This may require hydrolysis in the gastrointestinal tract and some sources speculate that it may be unsuitable in people with diarrhea or feeding-tubes in the duodenum or jejunum.

[27] Entamoeba histolytica invasive amebiasis is treated with metronidazole for eradication, in combination with diloxanide to prevent recurrence.

[29] 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).

[30] 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.

[31] However, the neurotoxic side effects occurring at the required dosages have prevented the widespread use of metronidazole as an adjuvant agent in radiation therapy.

[32] 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.

Infrequent adverse effects include: hypersensitivity reactions (rash, itch, flushing, fever), headache, dizziness, vomiting, glossitis, stomatitis, dark urine, and paraesthesia.

[37][38] Some evidence from studies in rats indicates the possibility it may contribute to serotonin syndrome, although no case reports documenting this have been published to date.

[41] Although some of the testing methods have been questioned, oral exposure has been shown to cause cancer in experimental animals and has also demonstrated some mutagenic effects in bacterial cultures.

[41][48] Metronidazole is listed as a possible carcinogen according to the World Health Organization (WHO) International Agency for Research on Cancer (IARC).

[49] A study in those with Crohn's disease also found chromosomal abnormalities in circulating lymphocytes in people treated with metronidazole.

One possible mechanism underlying this toxicity is that metronidazole may interference with postsynaptic central monoaminergic neurotransmission and immunomodulation.

[53] 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.

It is a prodrug that inhibits nucleic acid synthesis by forming nitroso radicals, which disrupt the DNA of microbial cells.

After the radical loses the electron to its target, it recycles back to the unactivated form of metronidazole, ready to be activated again.

[62] Oral metronidazole is approximately 80% bioavailable via the gut and peak blood plasma concentrations occur after one to two hours.

[62][66][67] Other mechanisms may include reduced drug activation, efflux pumps, altered redox potential and biofilm formation.

Studies have shown that metronidazole can decrease the production of reactive oxygen species (ROS) and nitric oxide by activated immune cells, such as macrophages and neutrophils.

Metronidazole's immunomodulatory properties are thought to be related to its ability to decrease the activation of nuclear factor-kappa B (NF-κB), a transcription factor that regulates the expression of pro-inflammatory cytokines, including chemokines, and adhesion molecules.

[81] Chemokines are a type of cytokines that act as chemoattractants, meaning they attract and guide immune cells to specific sites in the body where they are needed.

Metronidazole is used in the aquarium hobby to treat ornamental fish and as a broad-spectrum treatment for bacterial and protozoan infections in reptiles and amphibians.

The U.S. Food and Drug Administration (FDA) suggests it only be used when necessary because it has been shown to be carcinogenic in mice and rats, as well as to prevent antimicrobial resistance.

[99][100] The appropriate dosage of metronidazole varies based on the animal species, the condition being treated and the specific formulation of the product.