Metronidazole: Side Effects [US: Flagyl]
Generic Name: Metronidazole
Under what local brands and in what dosages is generic Metronidazole sold in pharmacies of Britain, United States, and Canada?
In pharmacies of the United States, Great Britain and Canada the pharmacists offer you to buy Metronidazole according to your prescription or without a prescription under such brand names and in such strengths and dosage forms:
| UK | US | Canada |
| Flagyl 200mg Tablets Flagyl 400mg Tablets Flagyl 500mg/100ml Solution Flagyl S Suspension Metrogel Metrolyl 1g Suppositories Metronidazole 200mg Tablets Metronidazole 400mg Tablets Metronidazole Tablets 500mg Norzol 200mg/5ml Oral Suspension Rozex Cream Rozex Gel Zidoval 7.5 mg/g Vaginal Gel Zyomet Gel | Flagyl 250mg Tablets Flagyl 375mg Capsules Flagyl 500mg Tablets Flagyl ER 750mg Tablets Flagyl I.V. 500mg Injectable Metrocream 0.75% Cream Metrogel 0.75% & 1% Gel Metronidazole 375mg Capsules Metronidazole 0.75% Cream Metronidazole 0.75% & 1% Gel Metronidazole 250mg Tablets Metronidazole 500mg Tablets Metronidazole 750mg Tablets Metronidazole 500mg/100ml Injectable | Flagyl 500mg Tablets Flagyl Cream 10% Flagystatin Vaginal OvulE 500mg Metrocream 0.75% Cream Metrogel 0.75% & 1% Gel Metronidazole 250mg Tablets Metronidazole 500mg Tablets Metronidazole 5mg/ml Injectable PMS-Metronidazole 250mg Tablets PMS-Metronidazole 500mg Tablets |
Metronidazole is a benzimidazole derivative.
Uses
Metronidazole is effective in the treatment of many protozoal diseases, notably trichomoniasis, amebiasis, schistosomiasis, strongyloidiasis, and giardiasis, and has been in use for over 20 years.
For amebiasis there is still discussion about the use of a single high dose versus repeated lower doses, both as regards efficacy and adverse effects. The use of metronidazole against infections with anerobic bacteria has increased over the years, and with this indication the use of metronidazole in combination with many other drugs used by patients with conditions likely to develop secondary anaerobic bacterial infections.With increased use there is also a widespread and increasing incidence of resistance of various strains of bacteria. The use of metronidazole as an added medication merely “to make assurance double sure” is to be discouraged. It is to be especially discouraged in immunocompromised patients, because of the risk of emergence of resistant bacterial strains. With increased use there is also an increased number of reports of some more unusual adverse effects. Overall, metronidazole can still be considered safe, if used in generally recommended doses.
Metronidazole has been formulated as a vaginal gel (0.75%) for the treatment of bacterial vaginosis. A single daily 5-day regimen has been approved by the FDA and has been shown to be as effective as oral metronidazole. In the eradication of Helicobacter pylori, metronidazole plus bismuth is effective, but causes more adverse effects than omeprazole plus amoxicillin plus either clarithromy-cin or metronidazole.
Pharmacokinetics
Metronidazole has excellent systemic availability, and absorption after oral administration is not significantly affected by food. Peak serum concentrations occur about 1 hour after ingestion. Multiple doses every 6-8 hours result in some drug accumulation, the half-life averaging about 8 hours. There is a linear relation between dose and serum concentration. Rectal administration results in serum concentrations about half those seen after oral administration.
Systemic absorption after local use in the vagina is slow, maximum serum concentrations being reached only after 8-24 hours; they are only about 20% of those attained after oral administration.
Metronidazole is extensively metabolized, and only about 20% of the dose is excreted unchanged in the urine. Tissue concentrations are similar to serum concentrations, and metronidazole penetrates readily into the central nervous system. As with many metabolized drugs, the half-life is markedly prolonged in neonates; there is an inverse relation between gestational age and half-life.
Prolonged elimination times are also seen in the presence of serious liver disease. Preliminary case reports have suggested that azithromycin or metronidazole can improve ciclosporin-induced gingival hyperplasia.
General adverse effects
Metronidazole is generally well tolerated. With high doses and high-dose prolonged treatment, nausea, vomiting, and central nervous system symptoms ranging from headache and dizziness to neuritis can occur. The commonest reactions are nausea, a metallic taste in the mouth, furry tongue, and vulvovaginal irritation in patients who take metronidazole for bacterial vaginosis. Reports of pancreatitis, neuropathy, and optic neuritis call for caution. Hypersensitivity reactions are unusual, but rashes have been described.
Metronidazole: Organs and Systems
Long-Term Effects
Drug tolerance
Resistance of H. pylori to metronidazole was found in 30% of isolates in the Lebanon, 42% in Brazil, and 80-90% in Africa.
Mutagenicity
Mutagenicity of metronidazole has been demonstrated in some bacterial systems. Studies on breakages in single-stranded DNA in the lymphocytes of patients treated with metronidazole for Trichomonas vaginitis have suggested that such breakages were repaired after withdrawal.
Another study reported chromosomal aberrations in the lymphocytes of ten volunteers taking metronidazole. A mutagenic effect would theoretically be possible in patients with a DNA repair defect. There has been concern that metronidazole may be genotoxic, as there have been reports of mutagenicity in several bacterial species.
The genotoxic effects of metronidazole (250 mg bd for 10 days) and nalidixic acid (400 mg bd for 10 days) have been assessed in women with Trichomonas vaginalis infections. The genotoxic potential of these drugs was evaluated using a sister chromatid exchange test in peripheral blood lymphocytes. Metronidazole had no effect but nalidixic acid caused an increase in sister chromatid exchange frequency. This result confirms that there is little evidence of genotoxicity with metronidazole.
Tumorigenicity
Prolonged high-dose exposure of mice to metronidazole leads to an increased incidence of lung tumors, and in one study there was an increase in lymphoreticular neoplasia in female animals. These results, which caused much concern when first published, are probably non-specific and not relevant to humans; these and other neoplasms have also been induced in mice merely by varying the diet.
Several long-term follow-up studies in man have failed to demonstrate an excess cancer risk. There has been a single report of cancers in three patients with Crohn’s disease who had taken metronidazole for years, but they had also taken sulfasalazine and glucocorticoids, and this cannot be regarded as constituting reasonable evidence of a causal link.
Second-Generation Effects Teratogenicity
Tests for embryotoxicity and teratogenicity in different animal species have been negative, and there have been no reports of adverse effects on the fetus in pregnant women given metronidazole for trichomoniasis. Despite this, it is still wise to avoid metronidazole during the first trimester of pregnancy. In a retrospective cohort study using the national birth registry in Denmark, comparing 124 women who took the drug with 13 327 who did not, there was no evidence of any increased risk to the unborn child.
In a prospective case-control study in Israel of 857 pregnant women seeking telephone advice regarding gestational exposure to prescribed drugs, 228 women who had taken metronidazole were compared with 629 controls exposed to non-teratogenic agents.
The mean daily dose of metronidazole was 973 mg for a mean duration of 7.9 days; 90% had used the medication orally, 6% by suppository, and 4% intravenously. Most (86%) had been exposed to metronidazole in the first trimester of pregnancy. There was no difference in the rate of major congenital malformations between the groups (1.6 versus 1.4%), even after accounting for terminations due to prenatally diagnosed malformations.
Neonatal birth weight was reduced in the metronidazole group (3.2 versus 3.3 kg) and this was not explained by an earlier gestational age at delivery or a higher prematurity rate but may have been due to the underlying conditions for which metronidazole was prescribed. These findings agree with previous meta-analyses showing that the use of metronidazole in pregnancy is not associated with an increased risk of fetal abnormality, despite in vitro evidence of mutagenesis and inconsistent animal evidence of fetal abnormalities caused by metronidazole.
Lactation
Metronidazole is excreted in the breast milk. There were no adverse effects in nursing infants, but one should still be cautious in using metronidazole in nursing mothers.
Susceptibility Factors
Age
In a randomized trial in 100 Iranian children, mebendazole (200 mg tds for 5 days, n — was compared with metronidazole (5 mg/kg tds for 7 days, in giardiasis. The two drugs were equally effective (over 85% cure rates). There were no adverse effects of mebendazole, whereas nausea, anorexia, and metallic taste were respectively observed in 4.9, 6, and 24% of those taking metronidazole.
Metronidazole: Drug-Drug Interactions