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A slight but statistically significant increase in two common murine tumors, pulmonary and hepatic, was observed in a mouse carcinogenicity study, particularly in aged mice. Mice were dosed orally up to 30 mg/ kg (90 mg/ m 2 or 0.5 times the maximum daily human tramadol dosage of 185 mg/ m 2 ) for approximately two years, although the study was not done with the Maximum Tolerated Dose. This finding is not believed to suggest risk in humans. No such finding occurred in rat carcinogenic-ity study (dosing orally up to 30 mg/ kg, 180 mg/ m 2 , or 1 time the maximum daily human tramadol dosage). Tramadol was not mutagenic in the following assays: Ames Salmonella microsomal activation test, CHO/ HPRT mammalian cell assay, mouse lymphoma assay (in the absence of metabolic activation), dominant lethal mu-tation tests in mice, chromosome aberration test in Chinese hamsters, and bone marrow micronucleus tests in mice and Chinese hamsters. Weakly mutagenic results occurred in the presence of metabolic activation in the mouse lymphoma assay and micronucleus test in rats. Overall, the weight of evidence from these tests indicates that tramadol does not pose a genotoxic risk to humans. Text Continues Below
No effects on fertility were observed for tramadol at oral dose levels up to 50 mg/ kg (350 mg/ m 2 ) in male rats and 75 mg/ kg (450 mg/ m 2 ) in female rats. These dosages are 1.6 and 2.4 times the maximum daily human tram-adol dosage of 185 mg/ m 2 . Pregnancy Teratogenic Effects
Pregnancy Category C No drug-related teratogenic effects were observed in the progeny of rats treated orally with tramadol and acetaminophen. The tramadol/ acetaminophen combi-nation product was shown to be embryotoxic and fetotoxic in rats at a maternally toxic dose, 50/ 434 mg/ kg tramadol/ acetaminophen (300/ 2604 mg/ m 2 or 1.6 times the maximum daily human tramadol/ acetaminophen dosage of 185/ 1591 mg/ m 2 ), but was not teratogenic at this dose level. Embryo and fetal toxicity consisted of decreased fetal weights and increased supernumerary ribs. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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