DRUG INTERACTIONS
Carcinogenesis, Mutagenesis, Impairment of Fertility
Two-year carcinogenicity studies in animals have not been performed. Insulin was not mutagenic in the Ames bacterial reverse mutation test in the presence and absence of metabolic activation.
In Sprague-Dawley rats, a 6-month repeat-dose toxicity study was conducted with insulin inhalation powder at doses up to 5.8 mg/kg/day (compared to the clinical starting dose of 0.15 mg/kg/day, the rat high dose was 39 times or 8.3 times the clinical dose, based on either a mg/kg or a mg/m2 body surface area comparison). In Cynomolgus monkeys, a 6-month repeat-dose toxicity study was conducted with inhaled insulin at doses up to 0.64 mg/kg/day. Compared to the clinical starting dose of 0.15 mg/kg/day, the monkey high dose was 4.3 times or 1.4 times the clinical dose, based on either a mg/kg or a mg/m2 body surface area comparison. These were maximum tolerated doses based on hypoglycemia.
Compared to control animals, there were no treatment-related adverse effects in either species on pulmonary function, gross or microscopic morphology of the respiratory tract or bronchial lymph nodes. Similarly, there was no effect on cell proliferation indices in alveolar or bronchiolar area of the lung in either species.
Because recombinant human insulin is identical to the endogenous hormone, reproductive/fertility studies were not performed in animals.
Pregnancy
Teratogenic Effects
Pregnancy Category C
Animal reproduction studies have not been conducted with EXUBERA. It is also not known whether EXUBERA can cause fetal harm when administered to a pregnant woman or whether EXUBERA can affect reproductive capacity. EXUBERA should be given to a pregnant woman only if clearly needed.
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