Drug Interactions between fluconazole and zidovudine

Information for this minor interaction is available on the professional version.

Hepatotoxicity including lactic acidosis, severe hepatomegaly with steatosis, fulminant hepatitis, and hepatic failure has been associated with the use of some nucleoside reverse transcriptase inhibitors (NRTIs) alone or in combination with other antiretroviral agents. Therapy with NRTIs should be administered cautiously in patients with preexisting liver disease, a history of alcohol abuse, or hepatitis. Therapy should be suspended if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur. The use of abacavir is contraindicated in patients with moderate to severe liver dysfunction as its safety and efficacy have not been established in these patients.

Zidovudine (AZT) may cause bone marrow toxicity, most commonly manifested as granulocytopenia and anemia, particularly in patients with advanced, symptomatic HIV disease. Thrombocytopenia not related to HIV may also occasionally occur. Zidovudine should be given with extreme caution to patients with preexisting bone marrow depression (indicated by a granulocyte count below 1000 cells/mm3 or hemoglobin less than 9.5 g/dL) or blood dyscrasias. Routine blood counts are recommended, and generally should occur more frequently in patients with advanced HIV disease. Dosage reductions may be necessary.

Hepatotoxicity including lactic acidosis, severe hepatomegaly with steatosis, fulminant hepatitis, and hepatic failure has been associated with the use of some nucleoside reverse transcriptase inhibitors (NRTIs) alone or in combination with other antiretroviral agents. Therapy with NRTIs should be administered cautiously in patients with preexisting liver disease, a history of alcohol abuse, or hepatitis. Therapy should be suspended if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur. The use of abacavir is contraindicated in patients with moderate to severe liver dysfunction as its safety and efficacy have not been established in these patients.

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.

Prolonged use of certain nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine and telbivudine may commonly cause myopathy, including rare cases of rhabdomyolysis. The myopathy may be dose-related and is characterized by persistent, unexplained muscle aches and/or weakness in conjunction with increases in creatine phosphokinase (CPK) values. Therapy with these NRTIs should be administered cautiously in patients with preexisting myopathy or a myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. NRTI therapy should be interrupted if drug-related myopathy is suspected, and discontinued if myopathy is diagnosed.

Prolonged use of certain nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine and telbivudine may commonly cause myopathy, including rare cases of rhabdomyolysis. The myopathy may be dose-related and is characterized by persistent, unexplained muscle aches and/or weakness in conjunction with increases in creatine phosphokinase (CPK) values. Therapy with these NRTIs should be administered cautiously in patients with preexisting myopathy or a myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. NRTI therapy should be interrupted if drug-related myopathy is suspected, and discontinued if myopathy is diagnosed.

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 apparent oral clearance of nucleoside reverse transcriptase inhibitors is decreased in patients with renal dysfunction. Dosage adjustments are recommended for lamivudine and stavudine in patients with CrCl less than 50 mL/min; zidovudine dosage should be reduced in patients with CrCl less than 15 mL/min. Fixed-dose combination products containing lamivudine are not recommended for patients with CrCl less than 30 or 50 mL/min; the manufacturer product information should be consulted.

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.