Drug Interactions between fluconazole and neratinib

Grapefruit juice can increase the blood levels of neratinib. This may increase the risk and/or severity of side effects such as diarrhea, nausea, vomiting, abdominal pain, mouth sores, loss of appetite, and liver problems. You should avoid the consumption of grapefruit and grapefruit juice during treatment with neratinib. Be sure to take the medication with food at the same time everyday to maintain consistent blood levels and effects. Talk to your doctor or pharmacist if you have questions on how to take this or other medications you are prescribed. 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 Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.

Neratinib is mainly metabolized in the liver and its use has been associated with hepatotoxicity characterized by increased liver enzymes. Patients with severe, preexisting hepatic impairment (Child Pugh Class C) experienced a reduction in neratinib clearance and an increase in C max and AUC. It is recommended to reduce the starting dose of neratinib to 80 mg in patients with severe hepatic impairment (Child Pugh C). Measure total bilirubin, AST, ALT, and alkaline phosphatase prior to starting treatment and monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. No dose modifications are recommended for patients with mild to moderate hepatic impairment (Child Pugh A or B).

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.