Cipol-N Drug Interactions

Nephrotoxic drugs: Interaction that may potentiate renal dysfunction are well substantiated between cyclosporine and various drugs, including aminoglycosides, vancomycin, co-trimoxazole, ciprofloxacin, melphalan, amphotericin B, ketoconazole, certain nonsteroidal anti-inflammatory agents (NSAIAs) (e.g., azapropazone, diclofenac, naproxen, sulindac), cimetidine, ranitidine, fibric acid derivatives (e.g., fenofibrate, bezafibrate), methotrexate, colchicine, and tacrolimus.
Concomitant administration of cyclosporine and colchicine may increase concentrations of cyclosporine, resulting in additive nephrotoxic effects. Cyclosporine also may reduce clearance of colchicine increasing the potential for enhanced colchicine toxicity (myopathy, neuropathy), particularly in patients with renal impairment. Patients should be monitored closely for colchicine toxicity during concurrent administration with cyclosporine; colchicine should be discontinued or dosage of the drug reduced if toxicity occurs.
Immunosuppressive and Antineoplastic agents: The modified formulations of cyclosporine may be administered with other immunosuppressives, although the degree of immunosuppression produced may result in an increased risk of lymphoma and other neoplasms and in susceptibility to infection.
Concomitant administration of cyclosporine and sirolimus substantially increases blood sirolimus concentrations. Sirolimus should be given 4 hours following cyclosporine administration to minimize the effect on sirolimus concentrations; concomitant administration of cyclosporine and methotrexate resulted in elevation of the AUC of methotrexate in patients with rheumatoid arthritis.
Potassium-sparing Drugs: Because cyclosporine may cause hyperkalemia, the drug should not be used concomitantly with potassium-sparing diuretics. Caution is advised and control of potassium concentrations recommended when cyclosporine is administered concomitantly with potassium-sparing drugs (e.g., angiotensin converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists) or potassium-containing drugs or in patients receiving a potassium-rich diet.
Drugs and Foods Affecting Hepatic Microsomal Enzymes: Because cyclosporine is extensively metabolized, the concentration of drug in biologic fluid (e.g., plasma, blood) may be altered by drugs or foods that effect hepatic microsomal enzymes, especially cytochrome P-450 isoenzyme subfamily CYP3A.
Drugs that decrease the metabolism and increase concentration of cyclosporine: diltiazem, nicardipine, verapamil, mibefradil, fluconazole, itraconazole, ketoconazole, voriconazole, clarithromycin, erythromycin, quinupristin/dalfopristin, methylprednisolone, allopurinol, amiodarone, bromocriptine, colchicine, imatinib, danazol, oral contraceptives, or metoclopramide.
Drugs that increase the metabolism and decrease concentration of cyclosporine: nafcillin, rifampin, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, octreotide, sulfinpyrazone, terbinafine, or ticlopidine.
Concomitant administration of cyclosporine with drugs that affect its metabolism requires monitoring of the concentration of cyclosporine in biologic fluid with appropriate adjustment of cyclosporine dosage.
Concomitant administration of prednisolone with cyclosporine may result in decreased plasma clearance of prednisolone, and plasma concentrations of cyclosporine may be increased during concomitant therapy with cyclosporine and methylprednisolone.
Concomitant oral administration of grapefruit juice with cyclosporine has been reported to increase bioavailability of cyclosporine.
The possibility that the immune response to vaccination may be diminished in patients receiving cyclosporine should be considered. In addition, because of the immunosuppressive effects of cyclosporine, the manufacturers recommend that live vaccines be avoided during therapy with the drug.
Concomitant administration of cyclosporine and metoclopramide has resulted in increased area under the blood concentration-time curve of cyclosporine. It has been suggested that absorption of cyclosporine increased through acceleration of gastric emptying of the drug stimulated by metoclopramide.
Concomitant use of cyclosporine and orlistat should be avoided because of the potential for decreased cyclosporine absorption.
Concomitant use of bosentan and cyclosporine has resulted in decreased plasma cyclosporine concentrations by approximately 50% and increased steady state plasma bosentan concentrations by about 3- to 4- fold.
Concomitant administration of cyclosporine and digoxin has resulted in decrease in apparent volume of distribution and serum clearance of digoxin. Cardiac glycoside toxicity (e.g., bidirectional ventricular tachycardia, anorexia, nausea, vomiting, diarrhea) occurred and serum digoxin concentrations were increased within a few days after patients already receiving digoxin began receiving cyclosporine.