Interaction entre Ciclosporine et Répaglinide

Cyclosporine may reduce the clearance of digoxin, colchicine, prednisolone, HMG-CoA reductase inhibitors (statins), aliskiren, bosentan, dabigatran, repaglinide, NSAIDs, sirolimus, etoposide, and other drugs.

Repaglinide Cyclosporine may increase the plasma concentrations of repaglinide and thereby increase the risk of hypoglycemia.

In 12 healthy male subjects who received two doses of 100 mg cyclosporine capsule orally 12 hours apart with a single dose of 0.25 mg repaglinide tablet (one-half of a 0.5 mg tablet) orally 13 hours after the cyclosporine initial dose, the repaglinide mean C max and AUC were increased 1.8-fold (range, 0.6 to 3.7-fold) and 2.4-fold (range, 1.2 to 5.3-fold), respectively.

Close monitoring of blood glucose level is advisable for a patient taking cyclosporine and repaglinide concomitantly.

Caution is also required when cyclosporine is coadministered with potassium sparing drugs (e.g., angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists), potassium-containing drugs as well as in patients on a potassium rich diet.

Cyclosporine Clinical Impact: Cyclosporine increased low dose repaglinide exposures by 2.5 fold [see Clinical Pharmacology (12.3) ] Intervention: Daily maximum repaglinide tablets dose should be limited to 6 mg, and increased frequency of glucose monitoring may be required when repaglinide tablets are co-administered with cyclosporine.

Cyclosporine : Limit daily dose of repaglinide to 6 mg and increase frequency of glucose monitoring when co-administered ( 7 )

CYP2C8 and CYP3A4 Inhibitors Intervention: Repaglinide tablets dose reductions and increased frequency of glucose monitoring may be required when co‑administered.

CYP2C8 and CYP3A4 Inhibitors and Drugs That May Increase the Risk of Hypoglycemia : Co-administration may require repaglinide tablets dose reductions and increased frequency of glucose monitoring ( 7 )

Examples: Drugs that are known to inhibit CYP3A4 include antifungal agents (ketoconazole, itraconazole) and antibacterial agents (clarithromycin, erythromycin).