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Drug Interactions between Halfan and perflutren

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

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Interactions between your drugs

Major

perflutren halofantrine

Applies to: perflutren and Halfan (halofantrine)

CONTRAINDICATED: 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 may be considered contraindicated 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

Major

halofantrine food

Applies to: Halfan (halofantrine)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentration of halofantrine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. After administration of 500 mg with 250 mL regular-strength grapefruit juice daily for 3 days, average halofantrine AUC increased 2.8-fold and peak plasma concentrations increased 3.2-fold, compared to water, in healthy subjects (n=12). QT interval prolongation increased from an average of 17 ms with water to 31 ms with grapefruit juice. Halofantrine, even at recommended doses, can cause dose-related prolongation of the QT interval, resulting in an elevated risk of potentially fatal ventricular arrhythmias including ventricular tachycardia and torsade de pointes.

ADJUST DOSING INTERVAL: The presence of food may increase the absorption and toxicity of halofantrine. Peak plasma concentrations increased seven-fold and AUC increased three-fold in healthy subjects when halofantrine was administered with high-fat food.

MANAGEMENT: The authors of the study recommend that grapefruit juice be avoided during halofantrine therapy. The manufacturer recommends performing an ECG before initiating halofantrine therapy and cardiac monitoring during and for 8 to 12 hours after completion of therapy. Halofantrine should be taken on an empty stomach at least 1 hour before or 2 hours after food.

References

  1. Giao PT, de Vries PJ (2001) "Pharmacokinetic interactions of antimalarial agents." Clin Pharmacokinet, 40, p. 343-73
  2. (2003) "Product Information. Halfan (halofantrine)." GlaxoSmithKline
  3. Charbit B, Becquemont L, Lepere B, Peytavin G, Funck-Bretano C (2002) "Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine." Clin Pharmacol Ther, 72, p. 514-23
  4. Abernethy DR, Wesche DL, Barbey JT, et al. (2001) "Stereoselective halofantrine disposition and effect: concentration-related QTc prolongation." Br J Clin Pharmacol, 51, p. 231-7
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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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