Metronidazole is primarily used to treat: 

bacterial vaginosis, pelvic inflammatory disease (along with

other antibacterials like ceftriaxone), pseudomembranous colitis, aspiration
pneumonia, rosacea (topical), fungating wounds (topical), intra-abdominal infections, lung
abscess, periodontitis, amoebiasis, oral infections, giardiasis, trichomoniasis, and infections caused
by susceptible anaerobic organisms such
as Bacteroides, Fusobacterium, Clostridium, Peptostreptococcus, and Prevotella species.[13] It is
also often used to eradicate Helicobacter pylori along with other drugs and to prevent infection in
people recovering from surgery.[13]
Metronidazole is bitter and so the liquid suspension contains metronidazole benzoate. 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. [14][15]

Bacterial vaginosis[edit]
Drugs of choice for the treatment of bacterial vaginosis include metronidazole and clindamycin. The
treatment of choice for bacterial vaginosis in nonpregnant women include metronidazole oral twice
daily for seven days, or metronidazole gel intravaginally once daily for five days, or clindamycin
intravaginally at bedtime for seven days. For pregnant women, the treatment of choice is
metronidazole oral three times a day for seven days. Data does not report routine treatment of male
sexual partners.[16]

Trichomoniasis[edit]
The 5-nitroimidazole drugs (metronidazole and tinidazole) are the mainstay of treatment for infection
with Trichomonas vaginalis. Treatment for both the infected patient and the patient's sexual partner
is recommended, even if asymptomatic. Therapy other than 5-nitroimidazole drugs is also an option,
but cure rates are much lower.[17]

Giardiasis[edit]
Oral metronidazole is a treatment option for giardiasis, however, the increasing incidence
of nitroimidazole resistance is leading to the increased use of other compound classes. [18]

Dracunculus[edit]
In the case of Dracunculus medinensis (Guinea worm), metronidazole just eases worm extraction
rather than killing the worm.[5]

C. difficile colitis[edit]
Initial antibiotic therapy for less-severe Clostridioides difficile infection colitis (pseudomembranous
colitis) consists of metronidazole, vancomycin, or fidaxomicin by mouth.[6] In 2017, the IDSA
generally recommended vancomycin and fidaxomicin over metronidazole. [6] Vancomycin by
mouth has been shown to be more effective in treating people with severe C. difficile colitis.[19]

E. histolytica[edit]
Entamoeba histolytica invasive amebiasis is treated with metronidazole for eradication, in
combination with diloxanide to prevent recurrence.[20] Although it is generally a standard treatment it
is associated with some side effects.[21]

Preterm births[edit]
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.[22]

Hypoxic radiosensitizer[edit]
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.
[23]
 However, the neurotoxic side effects occurring at the required dosages have prevented the
widespread use of metronidazole as an adjuvant agent in radiation therapy. [24] 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.[25]

Perioral dermatitis[edit]
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.[26][27]

Adverse effects[edit]
Common adverse drug reactions (≥1% of those treated with the drug) associated with systemic
metronidazole therapy include: nausea, diarrhea, weight loss, abdominal pain, vomiting, headache,
dizziness, and metallic taste in the mouth. Intravenous administration is commonly associated
with thrombophlebitis. Infrequent adverse effects include: hypersensitivity reactions (rash, itch,
flushing, fever), headache, dizziness, vomiting, glossitis, stomatitis, dark urine, and paraesthesia.
[13]
 High doses and long-term systemic treatment with metronidazole are associated with the
development of leucopenia, neutropenia, increased risk of peripheral neuropathy, and central
nervous system toxicity.[13] Common adverse drug reaction associated with topical metronidazole
therapy include local redness, dryness and skin irritation; and eye watering (if applied near eyes). [13]
[28]
 Metronidazole has been associated with cancer in animal studies. [29][failed verification] In rare cases, it can
also cause temporary hearing loss that reverses after cessation of the treatment. [30][31]
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. [32][33]

Mutagenesis and carcinogenesis[edit]

In 2016 metronidazole was listed by the U.S. National Toxicology Program (NTP) as reasonably
anticipated to be a human carcinogen.[34] 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. [34][35] The relationship between exposure
to metronidazole and human cancer is unclear. [34][36] One study [37] found an excess in lung cancer
among women (even after adjusting for smoking), while other studies [38][39][40] found either no
increased risk, or a statistically insignificant risk.[34][41] Metronidazole is listed as a possible carcinogen
according to the World Health Organization (WHO) International Agency for Research on
Cancer (IARC).[42] A study in those with Crohn's disease also found chromosomal abnormalities in
circulating lymphocytes in people treated with metronidazole. [35]

Stevens–Johnson syndrome[edit]
Metronidazole alone rarely causes Stevens–Johnson syndrome, but is reported to occur at high
rates when combined with mebendazole.[43]

Drug interactions[edit]
Alcohol[edit]
See also: Disulfiram-like drug
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.[44] People are often advised not to drink alcohol during
systemic metronidazole therapy and for at least 48 hours after completion of treatment. [13] However,
some studies call into question the mechanism of the interaction of alcohol and metronidazole, [45][46]
[47]
 and a possible central toxic serotonin reaction for the alcohol intolerance is suggested.
[32]
 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. [medical citation needed]

Other drug interactions[edit]

Metronidazole is a moderate CYP2C9 inhibitor. CYP2C9 is an enzyme of cytochrome P450 family.
Therefore, metronidazole may interact with medications metabolized by this enzyme. [48][49][50] Examples
of such medications are lomitapide, warfarin, etc.[2]

Pharmacology[edit]
Mechanism of action[edit]
Metronidazole is of the nitroimidazole class. It inhibits nucleic acid synthesis by
forming nitroso radicals, which disrupt the DNA of microbial cells.[2][51] This function only occurs when
metronidazole is partially reduced, and because this reduction usually happens only in anaerobic
bacteria and protozoans, it has relatively little effect upon human cells or aerobic bacteria.[52]

Pharmacokinetics[edit]

Hydroxymetronidazole, the main metabolite

Oral metronidazole is approximately 80% bioavailable via the gut and peak blood

plasma concentrations occur after one to two hours. Food may slow down absorption but does not
diminish it. Of the circulating substance, about 20% is bound to plasma proteins. It penetrates well
into tissues, the cerebrospinal fluid, the amniotic fluid and breast milk, as well as
into abscess cavities.[51]
About 60% of the metronidazole is metabolized by oxidation to the main
metabolite hydroxymetronidazole and a carboxylic acid derivative, and by glucuronidation. The
metabolites show antibiotic and antiprotozoal activity in vitro.[51] Metronidazole and its metabolites are
mainly excreted via the kidneys (77%) and to a lesser extent via the faeces (14%). [2][3] The biological
half-life of metronidazole in healthy adults is eight hours, in infants during the first two months of their
lives about 23 hours, and in premature babies up to 100 hours.[51]
The biological activity of hydroxymetronidazole is 30% to 65%, and the elimination half-life is longer
than that of the parent compound. [53] The serum half-life of hydroxymetronidazole
after suppository was 10 hours, 19 hours after intravenous infusion, and 11 hours after a tablet. [54]

History[edit]
The drug was initially developed by Rhône-Poulenc in the 1950s[55] and licensed to G.D. Searle.
[56]
 Searle was acquired by Pfizer in 2003. [57] The original patent expired in 1982,
but evergreening reformulation occurred thereafter.[58]

Brand name[edit]
In India, it is sold under the brand name Metrogyl and Flagyl. [59] In Bangladesh, it is available as
Amodis, Amotrex, Dirozyl, Filmet, Flagyl, Flamyd, Metra, Metrodol, Metryl, etc.[60] In Pakistan, it is
sold under the brand name of Flagyl and Metrozine.

Synthesis[edit]
2-Methylimidazole (1) may be prepared via the Debus-Radziszewski imidazole synthesis, or
from ethylenediamine and acetic acid, followed by treatment with lime, then Raney nickel. 2-
Methylimidazole is nitrated to give 2-methyl-4(5)-nitroimidazole (2), which is in
turn alkylated with ethylene oxid
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