Drug Interactions between fluconazole and pemigatinib

Pemigatinib may be taken with or without food. Do not consume grapefruit, grapefruit juice, or any supplements that contain grapefruit extract during treatment with pemigatinib unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of pemigatinib. This may increase the frequency and severity of serious side effects such as elevated phosphate levels in the blood (which can eventually lead to low blood calcium levels; calcium deposits in the skin, muscles, and other tissues; anemia; muscle cramps; seizures; and irregular heart rhythm), eye and vision problems, joint pain, mouth sores and inflammation, hair loss, diarrhea, nausea, vomiting, and constipation. Talk to your doctor if you have any questions or concerns. 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 Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.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.

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 recommended dosage of pemigatinib should be reduced in patients with severe hepatic dysfunction. No dose adjustment is recommended for patients with mild or moderate hepatic impairment.

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.

The recommended dosage of pemigatinib should be reduced in patients with severe renal disease. No dose adjustment is recommended for patients with mild or moderate renal impairment, or those patients with end-stage renal disease receiving intermittent hemodialysis.

Pemigatinib can cause retinal pigment epithelial detachment (RPED), which may cause symptoms such as blurred vision, visual floaters, or photopsia. A comprehensive ophthalmological examination including an optical coherence tomography should be performed prior to treatment initiation. Patients with visual disturbances should be closely monitored.