Drug Interactions between clopidogrel and fluconazole

Clopidogrel is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage.

The use of fluconazole has been rarely associated with hepatotoxicity. Reversible idiosyncratic hepatitis, cholestasis and fatal fulminant hepatic failure have been reported, the latter occurring primarily in patients with serious underlying medical conditions and taking multiple concomitant medications. Liver function tests should be performed periodically in patients with preexisting hepatic abnormalities, particularly during prolonged therapy. Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.

Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions, such as congenital/acquired QT prolongation, cardiomyopathy (especially when heart failure is present), sinus bradycardia, and existing symptomatic arrhythmias. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

Fluconazole is substantially removed by hemodialysis. Plasma levels of fluconazole has been shown to reduce by 50% following 3 hours of dialysis. Fluconazole should be administered after hemodialysis.

The pharmacokinetic disposition of clopidogrel in patients with liver disease has not been established. Clopidogrel undergoes biotransformation to an active metabolite that has not yet been isolated and an inactive form that represents approximately 85% of circulating clopidogrel. The metabolic and therapeutic activity of clopidogrel may be altered in patients with hepatic impairment and should be administered cautiously in patients with severe hepatic dysfunction. Clinical monitoring of hepatic function and bleeding activity is recommended.

Fluconazole is primarily eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from fluconazole due to decreased drug clearance. Dosage adjustments are recommended for patients with moderate to severe renal impairment (CrCl <= 50 mL/min) receiving multiple doses of the drug.

Clopidogrel is partially eliminated by the kidney. Approximately 50% of clopidogrel is excreted in the urine and 45% in the feces. Plasma concentrations of the inactive metabolite and the degree of platelet inhibition are reduced in patients with severe renal impairment (creatinine clearance of 5-15 mL/min). However, bleeding times in patients with severe renal impairment did not differ from those with normal renal function. No dosage adjustment is recommended for patients with compromised renal function.