Drug Interactions between doxorubicin and fluconazole

Myocardial damage, including acute left ventricular failure can occur with doxorubicin. The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 1% to 20% for cumulative doses ranging from 300 mg/m2 to 500 mg/m2 when doxorubicin is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Additionally, doxorubicin can also cause arrhythmias, including life-threatening events at any point during treatment. Assess LVEF before and regularly during and after treatment with doxorubicin. Doxorubicin is contraindicated in patients with severe myocardial insufficiency and recent myocardial infarction (past 6 months).

Doxorubicin induces dose-related myelosuppression, primarily affecting leukocytes. Therapy with doxorubicin should be withheld in patients whose bone marrow function is severely depressed by prior irradiation or chemotherapy or whose marrow function is recovering from previous cytotoxic therapy. If the need outweighs the risk, extreme caution should be exercised in administering doxorubicin and the dosage should be reduced. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitory of hematopoietic function is recommended. Doxorubicin is contraindicated in patients with severe persistent drug-induced myelosuppression

Doxorubicin induces dose-related myelosuppression, primarily affecting leukocytes. Therapy with doxorubicin should be withheld in patients whose bone marrow function is severely depressed by prior irradiation or chemotherapy or whose marrow function is recovering from previous cytotoxic therapy. If the need outweighs the risk, extreme caution should be exercised in administering doxorubicin and the dosage should be reduced. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitory of hematopoietic function is recommended. Doxorubicin is contraindicated in patients with severe persistent drug-induced myelosuppression

Myocardial damage, including acute left ventricular failure can occur with doxorubicin. The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 1% to 20% for cumulative doses ranging from 300 mg/m2 to 500 mg/m2 when doxorubicin is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Additionally, doxorubicin can also cause arrhythmias, including life-threatening events at any point during treatment. Assess LVEF before and regularly during and after treatment with doxorubicin. Doxorubicin is contraindicated in patients with severe myocardial insufficiency and recent myocardial infarction (past 6 months).

Doxorubicin induces dose-related myelosuppression, primarily affecting leukocytes. Therapy with doxorubicin should be withheld in patients whose bone marrow function is severely depressed by prior irradiation or chemotherapy or whose marrow function is recovering from previous cytotoxic therapy. If the need outweighs the risk, extreme caution should be exercised in administering doxorubicin and the dosage should be reduced. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitory of hematopoietic function is recommended. Doxorubicin is contraindicated in patients with severe persistent drug-induced myelosuppression

Myocardial damage, including acute left ventricular failure can occur with doxorubicin. The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 1% to 20% for cumulative doses ranging from 300 mg/m2 to 500 mg/m2 when doxorubicin is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Additionally, doxorubicin can also cause arrhythmias, including life-threatening events at any point during treatment. Assess LVEF before and regularly during and after treatment with doxorubicin. Doxorubicin is contraindicated in patients with severe myocardial insufficiency and recent myocardial infarction (past 6 months).

Because of their cytotoxic effects on rapidly proliferating tissues, antineoplastic agents frequently can, to varying extent, induce myelosuppression. The use of these drugs may be contraindicated in patients with known infectious diseases. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during antineoplastic therapy. Close clinical monitoring of hematopoietic function is recommended.

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.

Doxorubicin is contraindicated in patients with severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin level greater than 5 mg/dL). Doxorubicin is primarily metabolized by the liver and its clearance is reduced in the presence of hepatic dysfunction, increasing the risk for toxicity. Therapy with doxorubicin should be administered cautiously and at a reduced dosage in patients with moderate or mild hepatic function. Close clinical monitoring of hepatic function prior to initiation of doxorubicin therapy is recommended.

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.

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.