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Drug Interactions between lefamulin and Optison

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

perflutren lefamulin

Applies to: Optison (perflutren) and lefamulin

GENERALLY AVOID: 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: Concomitant use of perflutren lipid microsphere suspension with other agents that can prolong the QT interval should be avoided in some cases. 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.

References

  1. (2015) "Product Information. Definity (perflutren)." Lantheus Medical Imaging Inc
  2. (2015) "Product Information. Optison (perflutren)." Mallinckrodt Medical Inc

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Drug and food interactions

Moderate

lefamulin food

Applies to: lefamulin

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of lefamulin. When a single 600 mg oral dose of lefamulin was administered with a high-calorie, high-fat breakfast (800 to 1000 calories; approximately 50% from fat), lefamulin peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 23% and 18%, respectively.

GENERALLY AVOID: Grapefruit juice may increase the oral bioavailability of lefamulin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but pharmacokinetic data are available for the potent CYP450 3A4 inhibitor, ketoconazole. When oral lefamulin was administered with oral ketoconazole, mean lefamulin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 58% and 165%, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to lefamulin may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Lefamulin tablets should be taken at least one hour before or two hours after a meal. Patients should preferably avoid or limit the consumption of grapefruit and grapefruit juice during treatment with lefamulin.

References

  1. (2019) "Product Information. Xenleta (lefamulin)." Nabriva Therapeutics US, Inc.

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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