Drug Interaction Report

MONITOR: Coadministration with tarlatamab may increase the plasma concentrations of drugs that are substrates of CYP450 3A4 isoenzymes. Initiation of tarlatamab treatment causes transient release of cytokines that may suppress CYP450 isoenzymes, although the potential for interaction has not been studied. According to the manufacturer, the highest drug-drug interaction risk would be during and for up to 14 days after the occurrence of cytokine release syndrome.

MANAGEMENT: Caution is advised when tarlatamab is coadministered with drugs that are metabolized by CYP450 isoenzymes, particularly those with a narrow therapeutic range, where minimal changes to concentration may lead to significant adverse reactions, such as carbamazepine, colchicine, cyclosporine, disopyramide, phenytoin, quinidine, theophylline, warfarin, macrolide immunosuppressants, vinca alkaloids, and some narcotic analgesics. Clinical and/or laboratory monitoring are recommended, particularly during and after cytokine release syndrome, and individual product labeling for the CYP450 substrate(s) should be consulted for specific dosage adjustment recommendations.

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition. In addition, acute alcohol ingestion may potentiate CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam. Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient could consume orange juice which does not interact with these drugs. Patients should be advised to avoid alcohol during benzodiazepine therapy.