Flagyl ER (Metronidazole) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Drug/Laboratory test interactions

Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide (NAD⁺

Carcinogenesis, mutagenesis, impairment of fertility

Pulmonary tumors have been observed in all six reported studies in the mouse, including one study in which the animals were dosed on an intermittent schedule (administration during every fourth week only).

Malignant liver tumors were increased in male mice treated at approximately 1500 mg/m². This dose is approximately 3 times the recommended dose.

Malignant lymphomas and pulmonary neoplasms are also increased with lifetime feeding of the drug to mice (published data).

Mammary and hepatic tumors were increased among female rats administered oral metronidazole compared to concurrent controls.

Two lifetime tumorigenicity studies in hamsters have been performed and reported to be negative.

Metronidazole has shown mutagenic activity in in vitro assay systems including the Ames test. Studies in mammals in vivo have failed to demonstrate a potential for genetic damage. Fertility studies have been performed in mice at doses up to six times the maximum recommended human dose based on mg/m² and have revealed no evidence of impaired fertility.

Pregnancy

Teratogenic effects: Pregnancy Category B

Flagyl ER has not been studied in pregnant women. Since metronidazole crosses the placental barrier and enters the fetal circulation rapidly, it should not be administered to pregnant patients during the first trimester. No fetotoxicity was observed when metronidazole was administered orally to pregnant mice at 60 mg/ m²/day, which is approximately 10% of the human dose when expressed as mg/m². However, in a single small study where the drug was administered intraperitoneally, some intrauterine deaths were observed. The relationship of these findings to the drug is unknown. There are, however, no adequate and well-controlled studies in pregnant women. (See CONTRAINDICATIONS.)

Because animal reproduction studies are not always predictive of human response, and because metronidazole is a carcinogen in rodents, this drug should be used during pregnancy only if clearly needed.

OVERDOSAGE

Single oral doses of metronidazole, up to 15 g, have been reported in suicide attempts and accidental overdoses. Symptoms reported include nausea, vomiting, and ataxia.

Oral metronidazole has been studied as a radiation sensitizer in the treatment of malignant tumors. Neurotoxic effects, including seizures and peripheral neuropathy, have been reported after 5 to 7 days of doses of 6 g to 10.4 g every other day.

Treatment

There is no specific antidote for metronidazole overdose; therefore, management of the patient should consist of symptomatic and supportive therapy.

CONTRAINDICATIONS

Flagyl ER 750 mg tablets are contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.

Flagyl ER, like other formulations of metronidazole-containing products, is contraindicated during the first trimester of pregnancy. (See PRECAUTIONS.)