Combivent - Side Effects & Drug Interactions

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Albuterol:

Like other agents in its class, albuterol caused a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium in a two-year study in the rat at dietary doses of 2, 10 and 50 mg/ kg/ day (approximately 20, 100 and 500 times the maximum recommended human daily inhalation dose on a mg/ m 2 basis). In another study this effect was blocked by the co-administration of propranolol. The relevance of these findings to humans is not known. An 18-month study in mice at dietary doses up to 500 mg/ kg/ day (approximately 2500 times the maximum recommended human daily inhalation dose on a mg/ m 2 basis) and a 99-week study in hamsters at oral doses up to 50 mg/ kg/ day (approximately 375 times the maximum recommended human daily inhalation dose on a mg/ m 2 basis) revealed no evidence of tumorigenicity. Studies with albuterol revealed no evidence of mutagenesis. Reproduction studies in rats with albuterol sulfate revealed no evidence of impaired fertility.

Pregnancy

TERATOGENIC EFFECTS

Pregnancy Category C

Ipratropium bromide:

Pregnancy Category B. Oral reproduction studies were performed at doses of 10 mg/ kg in mice, 100 mg/ kg in rats and 125 mg/ kg in rabbits. These doses correspond, in each species, respectively, to approximately 300, 600 and 15, 000 times the maximum recommended human daily inhalation dose on a mg/ m 2 basis. Inhalation reproduction studies were conducted in rats and rabbits at doses of 1.5 and 1.8 mg/ kg/ day (approximately 90 and 210 times the maximum recommended human daily inhalation dose on a mg/ m 2 basis). These studies have demonstrated no evidence of teratogenic effects as a result of ipratropium bromide.

Albuterol:

Pregnancy Category C.

Albuterol has been shown to be teratogenic in mice. A reproduction study in CD-1 mice given albuterol subcutaneously (0. 025, 0.25 and 2. 5 mg/ kg) showed cleft palate formation in 5 of 111 (4. 5%) fetuses at 0. 25 mg/ kg (equivalent to the maximum recommended human daily inhalation dose on a mg/ m 2 basis) and in 10 of 108 (9. 3%) fetuses at 2.5 mg/ kg (approximately 10 times the maximum recommended human daily inhalation dose on a mg/ m 2 basis). None was observed at 0.025 mg/ kg (approximately one-tenth the maximum recommended human daily inhalation dose). Cleft palate also occurred in 22 of 72 (30.5%) fetuses treated with 2.5 mg/ kg isoproterenol (positive control). A reproduction study with oral albuterol in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%) fetuses at 50 mg/ kg (approximately 1000 times the maximum recommended human daily inhalation dose on a mg/ m 2 basis).