Augmentin - Warnings & Precautions

(Page 3)

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Long-term studies in animals have not been performed to evaluate carcinogenic potential.

Mutagenesis

The mutagenic potential of Augmentin was investigated in vitro with an Ames test, a human lymphocyte cytogenetic assay, a yeast test and a mouse lymphoma forward mutation assay, and in vivo with mouse micronucleus tests and a dominant lethal test. All were negative apart from the in vitro mouse lymphoma assay where weak activity was found at very high, cytotoxic concentrations.

Impairment of Fertility:

Augmentin at oral doses of up to 1200 mg/ kg/ day (5.7 times the maximum human dose, 1480 mg/ m 2 /day, based on body surface area) was found to have no effect on fertility and reproductive performance in rats, dosed with a 2: 1 ratio formulation of amoxicillin: clavulanate.

Teratogenic effects. Pregnancy (Category B)

Reproduction studies performed in pregnant rats and mice given Augmentin at oral dosages up to 1200 mg/ kg/ day, equivalent to 7200 and 4080 mg/ m 2 /day, respectively (4.9 and 2.8 times the maximum human oral dose based on body surface area), revealed no evidence of harm to the fetus due to Augmentin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if needed.

Labor and Delivery

Oral ampicillin class antibiotics are generally poorly absorbed during labor. Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions and duration of contractions. However, it is not known whether the use of Augmentin in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary. In a single study in women with premature rupture of fetal membranes, it was reported that prophylactic treatment with Augmentin may be associated with an increased risk of necrotizing enterocolitis in neonates.

Nursing Mothers

Ampicillin class antibiotics are excreted in the milk; therefore, caution should be exercised when Augmentin is administered to a nursing woman.