Drug Interactions between Definity and Duo-Medihaler

MONITOR: Coadministration of beta-2 adrenergic agonists with other adrenergic agents may potentiate the risk of cardiovascular side effects. Beta-2 adrenergic agonists can produce clinically significant cardiovascular effects including increases in pulse rate and systolic or diastolic blood pressure as well as ECG changes such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression. The risk is lower when beta-2 adrenergic agonists are inhaled at normally recommended dosages. However, these effects may be more common when the drugs are administered systemically or when recommended dosages are exceeded.

MANAGEMENT: Caution is advised if beta-2 adrenergic agonists are used concomitantly with other adrenergic agents, particularly in patients with cardiovascular disorders such as coronary insufficiency, cardiac arrhythmias, hypertrophic obstructive cardiomyopathy, or hypertension. Blood pressure and heart rate should be closely monitored.

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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.

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