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Anesthetics The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with anesthetics may be potentiated by calcium channel blockers. When used concomitantly, anesthetics and calcium blockers should be titrated carefully. Cyclosporine Text Continues Below
A pharmacokinetic interaction between diltiazem and cyclosporine has been observed during studies involving renal and car-diac transplant patients. In renal and cardiac transplant recipients, a reduction of cyclosporine dose ranging from 15% to 48% was necessary to maintain cyclosporine trough concentrations similar to those seen prior to the addition of diltiazem. If these agents are to be administered concurrently, cyclosporine concentrations should be monitored, especially when diltiazem ther-apy is initiated, adjusted, or discontinued. The effect of cyclosporine on diltiazem plasma concentrations has not been evaluated. Carbamazepine Concomitant administration of diltiazem with carbamazepine has been reported to result in elevated serum levels of car-bamazepine (40% to 72% increase), resulting in toxicity in some cases. Patients receiving these drugs concurrently should be monitored for a potential drug interaction. Carcinogenesis, Mutagenesis, Impairment of Fertility A 24-month study in rats at oral dosage levels of up to 100 mg/ kg/ day and a 21-month study in mice at oral dosage lev-els of up to 30 mg/ kg/ day showed no evidence of carcinogenicity. There was also no mutagenic response in vitro or in vivo in mammalian cell assays or in vitro in bacteria. No evidence of impaired fertility was observed in a study performed in male and female rats at oral dosages of up to 100 mg/ kg/ day. Pregnancy Category C. Reproduction studies have been conducted in mice, rats, and rabbits. Administration of doses ranging from five to ten times greater (on a mg/ kg basis) than the daily recommended therapeutic dose has resulted in embryo and fetal lethality. These doses, in some studies, have been reported to cause skeletal abnormalities. In the perinatal/ postnatal stud-ies there was an increased incidence of stillbirths at doses of 20 times the human dose or greater. There are no well-controlled studies in pregnant women; therefore, use diltiazem in pregnant women only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers Diltiazem is excreted in human milk. One report suggests that concentrations in breast milk may approximate serum lev-els. If use of diltiazem is deemed essential, an alternative method of infant feeding should be instituted. Pediatric Use Safety and effectiveness in pediatric patients have not been established.
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