Drug Interaction Report

MONITOR: Coadministration with talquetamab may increase the plasma concentrations of drugs that are substrates of CYP450 isoenzymes. Treatment with talquetamab causes release of cytokines that may suppress the activity of CYP450 isoenzymes, although the potential for interactions has not been studied. According to the manufacturer, the highest drug-drug interaction risk would likely be observed from the initiation of talquetamab up to 14 days after the first treatment dose as well as during and after cytokine release syndrome.

MANAGEMENT: Caution is advised when talquetamab is coadministered with drugs that are primarily metabolized by CYP450 isoenzymes, particularly those with a narrow therapeutic index (e.g., antiarrhythmics, anticonvulsants, immunosuppressants, theophylline, warfarin) or sensitive substrates where increases in plasma levels may be substantial or undesirable (e.g., antineoplastic agents, benzodiazepines, ergot alkaloids, opioids, statins). Clinical and/or laboratory monitoring should be considered following the initiation or withdrawal of talquetamab, and the individual dosage of the concomitant agents may be adjusted as needed.

CONTRAINDICATED: The consumption of grapefruit juice has been associated with significantly increased plasma concentrations of terfenadine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. Terfenadine in high serum levels has been associated with prolongation of the QT interval and development of torsade de pointes, a potentially fatal ventricular arrhythmia.

MANAGEMENT: Due to the risk of cardiotoxicity, patients receiving the drug should be advised to avoid consumption of grapefruit products. Loratadine, cetirizine, and fexofenadine may be safer alternatives in patients who may have trouble adhering to the dietary restriction.

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.