Cyclosporine is extensively metabolized by CYP 3A isoenzymes, in particular CYP3A4, and is a substrate of the multidrug efflux transporter P- glycoprotein . Various agents are known to either increase or decrease plasma or whole blood concentrations of cyclosporine usually by inhibition or induction of CYP3A4 or P-glycoprotein transporter or both. Compounds that decrease cyclosporine absorption such as orlistat should be avoided. Appropriate Sandimmune (cyclosporine) dosage adjustment to achieve the desired cyclosporine concentrations is essential when drugs that significantly alter cyclosporine concentrations are used concomitantly. (See Blood Concentration Monitoring )
50 mg/m2 IV 30 to 60 minutes prior to induction of anesthesia, with repeat doses of 50 mg/m2/dose IV every 6 hours or as a continuous infusion until the patient has recovered, has been recommended. For patients with congenital adrenal hyperplasia (CAH), 2 mg/kg/dose IV at induction of anesthesia with repeat doses every 4 hours or as a continuous IV infusion for prolonged procedures or recovery times has also been recommended. Alternatively, an initial stress dose of 25 mg IM followed by IV doses equivalent to 3 to 4 times the daily maintenance dose divided every 6 hours has been recommended.
A slightly increased number of basophilic hepatic foci were observed in chronic rat studies with budesonide, and in carcinogenicity studies there was an increased incidence of primary hepatocellular neoplasms, astrocytomas (in male rats) and mammary tumours (female rats) observed. These tumours are probably due to the specific steroid receptor action, increased metabolic burden on the liver and anabolic effects, effects which are also known from other glucocorticosteroids in rat studies and therefore represent a class effect. No similar effects have ever been observed in man for budesonide, neither in clinical trials nor from spontaneous reports.