Drug Interactions between fluconazole and glasdegib

Grapefruit and grapefruit juice may increase the blood levels and effects of glasdegib. This can increase the risk of serious side effects such as an irregular heart rhythm, inflammation and ulceration of the digestive tract, low red or white blood cells, fever, low platelet levels, bleeding, and swelling. You should avoid consumption of grapefruit and grapefruit juice during treatment with glasdegib. Otherwise, you may need a dose adjustment and/or more frequent monitoring by your doctor to safely use this medication. 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.

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 Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.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

Patients treated with glasdegib can develop QTc prolongation and ventricular arrhythmias, including ventricular fibrillation and ventricular tachycardia. The clinical trial excluded patients with baseline QTc of greater than 470 ms or with a history of long QT syndrome or uncontrolled cardiovascular disease. Monitor electrocardiograms (ECGs) and electrolytes closely in patients under treatment. In patients with congenital long QT syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring is recommended. Interrupt glasdegib if QTc increases to greater than 500 ms, and discontinue permanently for patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia

Patients treated with glasdegib can develop QTc prolongation and ventricular arrhythmias, including ventricular fibrillation and ventricular tachycardia. The clinical trial excluded patients with baseline QTc of greater than 470 ms or with a history of long QT syndrome or uncontrolled cardiovascular disease. Monitor electrocardiograms (ECGs) and electrolytes closely in patients under treatment. In patients with congenital long QT syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring is recommended. Interrupt glasdegib if QTc increases to greater than 500 ms, and discontinue permanently for patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia

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.

Glasdegib has not been studied in patients with severe renal impairment or moderate-to-severe hepatic impairment. Caution is advised.

Patients treated with glasdegib can develop QTc prolongation and ventricular arrhythmias, including ventricular fibrillation and ventricular tachycardia. The clinical trial excluded patients with baseline QTc of greater than 470 ms or with a history of long QT syndrome or uncontrolled cardiovascular disease. Monitor electrocardiograms (ECGs) and electrolytes closely in patients under treatment. In patients with congenital long QT syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring is recommended. Interrupt glasdegib if QTc increases to greater than 500 ms, and discontinue permanently for patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia

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.

Glasdegib has not been studied in patients with severe renal impairment or moderate-to-severe hepatic impairment. Caution is advised.