Drug Interactions between fluconazole and ivosidenib

Do not consume grapefruit or grapefruit juice during treatment with ivosidenib unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of ivosidenib. This may increase the risk of an irregular heart rhythm that may be serious and potentially life-threatening. You may be more susceptible if you have a heart condition called congenital long QT syndrome, other cardiac diseases, conduction abnormalities, or electrolyte disturbances (for example, magnesium or potassium loss due to severe or prolonged diarrhea or vomiting). Talk to your doctor if you have any questions or concerns. You may take ivosidenib with or without food, but avoid taking it with a high-fat meal, as this can also increase blood levels of the medication. An example of a high-fat meal includes 2 eggs fried in butter, 2 strips of bacon, 2 slices of white bread with butter, 1 croissant with 1 slice of cheese, and 8 ounces of whole milk (approximately 1,000 calories and 58 grams of fat). You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart palpitations during treatment. 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 Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.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 ivosidenib can develop QTc prolongation and ventricular arrhythmias. Concomitant use of ivosidenib with drugs known to prolong the QTc interval (e.g., antiarrhythmic medicines, fluoroquinolones, triazole antifungals, 5-hydroxytryptamine-3 [5-HT3] receptor antagonists) and CYP450 3A4 inhibitors may increase the risk of QTc interval prolongation. ECGs and electrolytes should be monitored. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary. Treatment should be interrupted if QTc increases to greater than 480 and less than 500 msec. Ivosidenib should be interrupted and the dosage should be reduced if QTc increases to greater than 500 msec. Ivosidenib should be permanently discontinued in patients who develop QTc interval prolongation with signs/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.

Patients treated with ivosidenib can develop QTc prolongation and ventricular arrhythmias. Concomitant use of ivosidenib with drugs known to prolong the QTc interval (e.g., antiarrhythmic medicines, fluoroquinolones, triazole antifungals, 5-hydroxytryptamine-3 [5-HT3] receptor antagonists) and CYP450 3A4 inhibitors may increase the risk of QTc interval prolongation. ECGs and electrolytes should be monitored. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary. Treatment should be interrupted if QTc increases to greater than 480 and less than 500 msec. Ivosidenib should be interrupted and the dosage should be reduced if QTc increases to greater than 500 msec. Ivosidenib should be permanently discontinued in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia.

Patients treated with ivosidenib can develop QTc prolongation and ventricular arrhythmias. Concomitant use of ivosidenib with drugs known to prolong the QTc interval (e.g., antiarrhythmic medicines, fluoroquinolones, triazole antifungals, 5-hydroxytryptamine-3 [5-HT3] receptor antagonists) and CYP450 3A4 inhibitors may increase the risk of QTc interval prolongation. ECGs and electrolytes should be monitored. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary. Treatment should be interrupted if QTc increases to greater than 480 and less than 500 msec. Ivosidenib should be interrupted and the dosage should be reduced if QTc increases to greater than 500 msec. Ivosidenib should be permanently discontinued in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia.

Patients treated with ivosidenib can develop QTc prolongation and ventricular arrhythmias. Concomitant use of ivosidenib with drugs known to prolong the QTc interval (e.g., antiarrhythmic medicines, fluoroquinolones, triazole antifungals, 5-hydroxytryptamine-3 [5-HT3] receptor antagonists) and CYP450 3A4 inhibitors may increase the risk of QTc interval prolongation. ECGs and electrolytes should be monitored. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary. Treatment should be interrupted if QTc increases to greater than 480 and less than 500 msec. Ivosidenib should be interrupted and the dosage should be reduced if QTc increases to greater than 500 msec. Ivosidenib should be permanently discontinued in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia.

The pharmacokinetics and safety of ivosidenib in patients with severe renal dysfunction (estimated GFR less than 30 mL/min/1.73 m2, Modification of Diet in Renal Disease [MDRD]), renal dysfunction requiring dialysis, or severe liver dysfunction (Child-Pugh C) are unknown. The risks and potential benefits should be considered before starting ivosidenib in patients with preexisting severe renal dysfunction, preexisting severe liver dysfunction, or who are requiring dialysis. Caution is advised in these patients.

Patients treated with ivosidenib can develop QTc prolongation and ventricular arrhythmias. Concomitant use of ivosidenib with drugs known to prolong the QTc interval (e.g., antiarrhythmic medicines, fluoroquinolones, triazole antifungals, 5-hydroxytryptamine-3 [5-HT3] receptor antagonists) and CYP450 3A4 inhibitors may increase the risk of QTc interval prolongation. ECGs and electrolytes should be monitored. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary. Treatment should be interrupted if QTc increases to greater than 480 and less than 500 msec. Ivosidenib should be interrupted and the dosage should be reduced if QTc increases to greater than 500 msec. Ivosidenib should be permanently discontinued in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia.

Patients treated with ivosidenib can develop QTc prolongation and ventricular arrhythmias. Concomitant use of ivosidenib with drugs known to prolong the QTc interval (e.g., antiarrhythmic medicines, fluoroquinolones, triazole antifungals, 5-hydroxytryptamine-3 [5-HT3] receptor antagonists) and CYP450 3A4 inhibitors may increase the risk of QTc interval prolongation. ECGs and electrolytes should be monitored. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary. Treatment should be interrupted if QTc increases to greater than 480 and less than 500 msec. Ivosidenib should be interrupted and the dosage should be reduced if QTc increases to greater than 500 msec. Ivosidenib should be permanently discontinued in patients who develop QTc interval prolongation with signs/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.

The pharmacokinetics and safety of ivosidenib in patients with severe renal dysfunction (estimated GFR less than 30 mL/min/1.73 m2, Modification of Diet in Renal Disease [MDRD]), renal dysfunction requiring dialysis, or severe liver dysfunction (Child-Pugh C) are unknown. The risks and potential benefits should be considered before starting ivosidenib in patients with preexisting severe renal dysfunction, preexisting severe liver dysfunction, or who are requiring dialysis. Caution is advised in these patients.