Drug Interactions between PC-CAP and perflutren

MONITOR: Perflutren lipid microsphere suspension (Definity) has been reported to cause prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In 221 study subjects who received ECG monitoring at various time points from 1 to 72 hours following administration of perflutren lipid microsphere bolus doses of up to 10 microL/kg, QTc prolongations of >30 msec were noted in 64 (29%) subjects. Forty-six out of these 64 subjects were further evaluated, and 18 (39%) were found to have associated cardiac rhythm changes. The effects of concomitant drugs were not studied. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution is recommended if perflutren lipid microsphere suspension is used in combination with other drugs that can prolong the QT interval. Please refer to the prescribing information for these drugs for more information. No data are available regarding the effect of perflutren protein-type A microsphere suspension (Optison) on the QT interval of the electrocardiogram.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.