Cyclosporine administration

Sirolimus tablets - For simultaneous administration, mean C and AUC were increased by 512% and 148%, respectively, relative to administration of sirolimus alone. However, when given 4 hours after cyclosporine administration, sirolimus C and AUC were both increased by only 33% compared with administration of sirolimus alone. 

In contrast, data from a recent conference presentation by Choc and Robinson [100], indicated that cyclosporin metabolite ratios were similar after oral administration of either Sandimmun or the Neoral formulation, suggesting minimal changes in cyclosporin first-pass metabolism after Neoral administration. Furthermore, Neoral/Sandimmun area under the curve (AUC) ratios were similar (approximately 2) after cyclosporin administration in either the absence or presence of a CYP3A/P-gp inhibitor, whereas an AUC ratio of approximately 1 would have been expected if bioavailability was limited by metabolism or antitransport. However, these data have not yet been published, and the relative contributions of enhanced absorption or reduced metabolism in the CY bioavailability enhancement provided by Sandimmun Neoral are yet to be fully defined. 

Lopez-Calderon A, Soto L, Villanua MA, Vidarte L, Martin AI. The effect of cyclosporine administration on growth hormone release and serum concentrations of insulin-like growth factor-I in male rats. Life Sci 1999 64(17) 1473-83. 

Perico N,ZojaC, Benigni A,Ghilardi F, Gualandris L, RemuzziG. Effect of short-term cyclosporine administration in rats on renin-angiotensin and thromboxane A2 possible relevance to the reduction in glomerular filtration rate. J Pharmacol ExpTher 1986 239 229-235. 

Murray BM, Paller MS, FerrisTF. Effect of cyclosporine administration on renal hemodynamics in conscious rats. Kidney Int 1985 28 767-774. 

Ressureicao FA, Ballejo G, Salgado MC, Ferraz AS. Effect of cyclosporine administration on vascular reactivity of the isolated mesenteric bed.Transplant Proc 1995 27 1806-1808. 

The co-administration of drugs which induce the metabolic enzymes in the liver or small intestine can reduce the plasma concentrations of drugs which are substrates of the enzyme, leading to reduced drug effects. For example, the plasma concentrations of many drugs which are substrates of the enzyme CYP3A4, such as cyclosporine, are decreased by coadministration of rifampicin, which is an inducer of CYP3A4. 

Orlistat reduces the absorption of fat-soluble vitamins. Daily intake of a multivitamin containing vitamins A, D, E, and K, as well as 3-carotene, is recommended. Patients should take the multivitamin 2 hours prior to or after the dose of orlistat.31 Since availability of vitamin K may decline in patients receiving orlistat therapy, close monitoring of coagulation status should occur with concomitant administration of warfarin.31 Administration of orlistat in conjunction with cyclosporine can result in decreased cyclosporine plasma levels. To avoid this interaction, cyclosporine should be taken 2 hours preceding or following the dose of orlistat. Additionally, cyclosporine levels should be monitored more frequently.31... 

Age-related variations in central nervous system (CNS) neurotransmitter production and receptor sensitivity are the most likely explanations for the pharmacodynamic differences observed between children and adults following administration of psychotropic medications [39a], Children have lower phenobarbital ratios than adults, and the ratio increases with gestational age [40,41]. Conversely, a lower therapeutic range for children has been identified for cyclosporine, phenytoin, and digoxin [42]. 

Movsowitz, C., Epstein, S., Fallon, M., Ismail, F. and Thomas, S. (1988) Cyclosporin-A in vivo produces severe osteopenia in the rat - effect of dose and duration of administration. Endocrinology 123, 2571-2577. 

This antibody is raised against the protein-based CD3 antigen, present on the cell surface of most T-lymphocytes. I.v. administration of (unconjugated) antibody appears to block normal functioning of such T-cells and promote their clearance from the blood. However, upon cessation of antibody administration, CD3 positive cell numbers rapidly revert to normal values. Therefore, maintenance immunosuppressives (e.g. with cyclosporine) must subsequently be restored. 

Bekerman, T., J. Golenser, A. Domb, Cyclosporin Nanoparticle Lipospheres for Oral Administration, Journal of Pharmaceutical Sciences, 93, 1264, 2004. 

Renal function impairment For patients with severe renal insufficiency, do not start ezetimibe/simvastatin unless the patient has already tolerated treatment with simvastatin at a dose of 5 mg or higher. Exercise caution when ezetimibe/simvastatin is administered to these patients, and monitor them closely. Concomitant bile acid sequestrants Give ezetimibe/simvastatin either 2 hours or more before or 4 hours or more after administration of a bile acid sequestrant. Concomitant cyclosporine Exercise caution when initiating ezetimibe/simvastatin in the setting of cyclosporine. In patients taking cyclosporine, do not start ezetimibe/simvastatin unless the patient has already tolerated treatment with simvastatin at a dose of 5 mg or higher. Do not exceed 10 mg ezetimibe/10 mg simvastatin daily. 

Concurrent immunosuppressants Sirolimus has been administered concurrently with cyclosporine and corticosteroids. The efficacy and safety of the use of sirolimus in combination with other immunosuppressive agents have not been determined. Renai function impairment Mean serum creatinine was increased and mean glomerular filtration rate was decreased in patients treated with sirolimus and cyclosporine compared with those treated with cyclosporine and placebo or azathioprine controls. Monitor renal function during the administration of maintenance immunosuppression regimens including sirolimus in combination with cyclosporine, and consider appropriate adjustment of the immunosuppression... 

Hypersensitivity to polyoxyethylated castor oil (injection only see Warnings and Administration and Dosage), cyclosporine, or any component of the products Gengraf and Neoral in psoriasis or RA patients with abnormal renal function, uncontrolled hypertension, or malignancies Gengraf and A/eora/concomitantly with PUVA or DVB, methotrexate or other immunosuppressive agents, coal tar or radiation therapy in psoriasis patients. 

Drug/Food interactions Administration of food with A/eora/decreases the ADC and Cmax of cyclosporine. A high-fat meal consumed within 30 minutes of Neoral administration decreased the AUC by 13% and Cmax by 33%. The effects of a low-fat meal were similar. In addition, do not take cyclosporine simultaneously with grapefruit juice unless specifically instructed to do so trough cyclosporine concentrations may be increased. 

---