Drug Interactions between quizartinib and troleandomycin

Troleandomycin is primarily excreted by the liver and may accumulate in patients with impaired hepatic function. In addition, the use of troleandomycin has been associated with an allergic type of cholestatic hepatitis, particularly in patients receiving the drug for more than 2 weeks or given repeated courses. Therapy with troleandomycin should be administered cautiously in patients with liver and/or biliary disease. Liver function tests should be monitored during prolonged or repeated courses of therapy, and the drug discontinued if abnormalities develop.

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

Quizartinib prolongs the QT interval in a dose and concentration dependent manner. Due to the serious risk of QTc prolongation, quizartinib is contraindicated in patients with long QT syndrome, a history of ventricular arrhythmias or torsades de points, severe hypokalemia, or severe hypomagnesemia. Additionally, avoid use in patients who are at significant risk of developing torsades de pointes, including uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, tachyarrhythmias, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism. Perform an ECG and correct electrolyte abnormalities before and during treatment as indicated, especially in high-risk patients or during concomitant use with strong CYP450 3A4 inhibitors or drugs known to prolong the QT interval. Do not initiate or escalate therapy in patients with QTcF interval greater than 450 ms; dose adjustments based on QTcF interval may be required.

Quizartinib prolongs the QT interval in a dose and concentration dependent manner. Due to the serious risk of QTc prolongation, quizartinib is contraindicated in patients with long QT syndrome, a history of ventricular arrhythmias or torsades de points, severe hypokalemia, or severe hypomagnesemia. Additionally, avoid use in patients who are at significant risk of developing torsades de pointes, including uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, tachyarrhythmias, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism. Perform an ECG and correct electrolyte abnormalities before and during treatment as indicated, especially in high-risk patients or during concomitant use with strong CYP450 3A4 inhibitors or drugs known to prolong the QT interval. Do not initiate or escalate therapy in patients with QTcF interval greater than 450 ms; dose adjustments based on QTcF interval may be required.

Quizartinib prolongs the QT interval in a dose and concentration dependent manner. Due to the serious risk of QTc prolongation, quizartinib is contraindicated in patients with long QT syndrome, a history of ventricular arrhythmias or torsades de points, severe hypokalemia, or severe hypomagnesemia. Additionally, avoid use in patients who are at significant risk of developing torsades de pointes, including uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, tachyarrhythmias, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism. Perform an ECG and correct electrolyte abnormalities before and during treatment as indicated, especially in high-risk patients or during concomitant use with strong CYP450 3A4 inhibitors or drugs known to prolong the QT interval. Do not initiate or escalate therapy in patients with QTcF interval greater than 450 ms; dose adjustments based on QTcF interval may be required.

Quizartinib prolongs the QT interval in a dose and concentration dependent manner. Due to the serious risk of QTc prolongation, quizartinib is contraindicated in patients with long QT syndrome, a history of ventricular arrhythmias or torsades de points, severe hypokalemia, or severe hypomagnesemia. Additionally, avoid use in patients who are at significant risk of developing torsades de pointes, including uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, tachyarrhythmias, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism. Perform an ECG and correct electrolyte abnormalities before and during treatment as indicated, especially in high-risk patients or during concomitant use with strong CYP450 3A4 inhibitors or drugs known to prolong the QT interval. Do not initiate or escalate therapy in patients with QTcF interval greater than 450 ms; dose adjustments based on QTcF interval may be required.

Troleandomycin is primarily excreted by the liver and may accumulate in patients with impaired hepatic function. In addition, the use of troleandomycin has been associated with an allergic type of cholestatic hepatitis, particularly in patients receiving the drug for more than 2 weeks or given repeated courses. Therapy with troleandomycin should be administered cautiously in patients with liver and/or biliary disease. Liver function tests should be monitored during prolonged or repeated courses of therapy, and the drug discontinued if abnormalities develop.

Quizartinib prolongs the QT interval in a dose and concentration dependent manner. Due to the serious risk of QTc prolongation, quizartinib is contraindicated in patients with long QT syndrome, a history of ventricular arrhythmias or torsades de points, severe hypokalemia, or severe hypomagnesemia. Additionally, avoid use in patients who are at significant risk of developing torsades de pointes, including uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, tachyarrhythmias, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism. Perform an ECG and correct electrolyte abnormalities before and during treatment as indicated, especially in high-risk patients or during concomitant use with strong CYP450 3A4 inhibitors or drugs known to prolong the QT interval. Do not initiate or escalate therapy in patients with QTcF interval greater than 450 ms; dose adjustments based on QTcF interval may be required.

Midostaurin and quizartinib should be used with caution in patients with severe hepatic or severe renal dysfunction as the pharmacokinetics of these agents have not been studied in these patients. No dosage adjustments are recommended in patients with mild or moderate hepatic or renal dysfunction.

Midostaurin and quizartinib should be used with caution in patients with severe hepatic or severe renal dysfunction as the pharmacokinetics of these agents have not been studied in these patients. No dosage adjustments are recommended in patients with mild or moderate hepatic or renal dysfunction.