Drug Interactions between fluconazole and nilotinib

Do not consume grapefruit or grapefruit juice during treatment with nilotinib unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of nilotinib to dangerous levels, increasing the risk of an irregular heart rhythm that may be serious. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart palpitations during treatment with nilotinib. Food may also increase the blood levels of nilotinib. Therefore, you should take nilotinib on an empty stomach, meaning no food should be eaten for at least two hours before or one hour after taking nilotinib. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Nilotinib should not be used in patients with hypokalemia, hypomagnesemia or long QT syndrome, as it has shown to prolong QT interval in a concentration-dependent manner. This can cause a ventricular tachycardia called Torsade de Pointes which can result in syncope, seizures, and/or death. Before initiating nilotinib, electrolytes should be tested. Hypokalemia or hypomagnesemia should be corrected before starting treatment and monitored periodically. Patients at risk should be monitored with an EKG before and during treatment as clinically indicated and dose adjustments might be needed.

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 Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.

Nilotinib should not be used in patients with hypokalemia, hypomagnesemia or long QT syndrome, as it has shown to prolong QT interval in a concentration-dependent manner. This can cause a ventricular tachycardia called Torsade de Pointes which can result in syncope, seizures, and/or death. Before initiating nilotinib, electrolytes should be tested. Hypokalemia or hypomagnesemia should be corrected before starting treatment and monitored periodically. Patients at risk should be monitored with an EKG before and during treatment as clinically indicated and dose adjustments might be needed.

Nilotinib should not be used in patients with hypokalemia, hypomagnesemia or long QT syndrome, as it has shown to prolong QT interval in a concentration-dependent manner. This can cause a ventricular tachycardia called Torsade de Pointes which can result in syncope, seizures, and/or death. Before initiating nilotinib, electrolytes should be tested. Hypokalemia or hypomagnesemia should be corrected before starting treatment and monitored periodically. Patients at risk should be monitored with an EKG before and during treatment as clinically indicated and dose adjustments might be needed.

Nilotinib can cause increases in serum lipase. Patients with a previous history of pancreatitis might be at increased risk and should be monitored carefully for lipase elevations and any abdominal symptoms. Serum lipase should be monitored monthly or as clinically indicated and treatment might need to be interrupted until pancreatitis is excluded as a diagnosis.

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.

Thrombocytopenia, aplastic anemia, agranulocytosis and neutropenia occur with BCR-ABL tyrosine kinase inhibitors. Therapy with these drugs should be administered cautiously in patients with preexisting bone marrow suppression. A complete blood count should be performed every 1-2 weeks for the first month of therapy and then monthly thereafter, or as clinically indicated. To manage myelosuppression, withhold, reduce dose, or discontinue therapy as necessary.

Cardiovascular events, including arterial vascular occlusive events, peripheral arterial occlusive events and ischemic cerebrovascular events have been reported in patients receiving tyrosine kinase inhibitors. If acute signs or symptoms of cardiovascular events occur, patients should seek immediate medical attention. The cardiovascular status and risk factors of patients should be evaluated prior to therapy and cardiovascular monitoring and management should take place during treatment.

Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.

Nilotinib can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia. Electrolyte abnormalities should be corrected prior to initiating nilotinib and during therapy, and should be monitored periodically.

Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.

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.

Nilotinib capsules contain lactose, so it is not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency with a severe degree of intolerance to lactose- containing products, or of glucose-galactose malabsorption.

Nilotinib exposure is increased in patients with hepatic impairment. The use of a lower starting dose might be needed. Additionally, there have been reports of hepatotoxicity as measured by elevations in bilirubin, AST, ALT and alkaline phosphatase. Liver function should be monitored before initiation of treatment and regularly during therapy. Dose reduction or interruption might be needed if laboratory abnormalities are found.

Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.

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.