Dofetilid ve Ketokonazol etkileşimi

QT Prolongation and Drug Interactions Leading to QT Prolongation Coadministration of the following drugs with ketoconazole is contraindicated: dofetilide, quinidine, pimozide, lurasidone, cisapride, methadone, disopyramide, dronedarone, ranolazine.

CONTRAINDICATIONS Drug Interactions Coadministration of a number of CYP3A4 substrates such as dofetilide, quinidine cisapride and pimozide is contraindicated with ketoconazole tablets.

Coadministration of the following drugs with ketoconazole is contraindicated: dofetilide, quinidine, pimozide, lurasidone, cisapride, methadone, disopyramide, dronedarone, ranolazine.

Antiarrhythmics disopyramide, dofetilide, dronedarone, quinidine digoxin Disopyramide, dofetilide, dronedarone, quinidine: The potential increase in plasma concentrations of these drugs when coadministered with ketoconazole may increase the risk of serious cardiovascular events including QT prolongation.

The concomitant use of verapamil or the cation transport system inhibitors cimetidine, trimethoprim (alone or in combination with sulfamethoxazole), or ketoconazole with dofetilide is contraindicated (see WARNINGS and PRECAUTIONS, Drug-Drug Interactions ), as each of these drugs cause a substantial increase in dofetilide plasma concentrations.

The magnitude of the effect on renal elimination by cimetidine, trimethoprim, and ketoconazole (all contraindicated concomitant uses with dofetilide) suggests that all renal cation transport inhibitors should be contraindicated.

Ketoconazole: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of ketoconazole is contraindicated.

Use with Drugs that Prolong QT Interval and Antiarrhythmic Agents The use of dofetilide in conjunction with other drugs that prolong the QT interval has not been studied and is not recommended.

Ketoconazole at 400 mg daily (the maximum approved prescription dose) co-administered with dofetilide (500 mcg BID) for 7 days has been shown to increase dofetilide C max by 53% in males and 97% in females, and AUC by 41% in males and 69% in females.