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Drug Interactions between halofantrine and Lariam

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

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Interactions between your drugs

Major

mefloquine halofantrine

Applies to: Lariam (mefloquine) and halofantrine

CONTRAINDICATED: Coadministration of halofantrine and mefloquine may have additive prolonging effects on the QT interval. The risk of ventricular arrhythmias including ventricular tachycardia and torsade de pointes may be increased. Death has been reported with this combination.

MANAGEMENT: Halofantrine should not be administered with mefloquine or within 15 weeks of the last dose of mefloquine due to increased risk of potentially fatal prolongation of the QTc interval. The manufacturer recommends performing an ECG before initiating halofantrine therapy and monitoring cardiac rhythm during and for 8 to 12 hours after completion of therapy.

References

  1. "Product Information. Mefloquine Hydrochloride (mefloquine)." Hikma USA (formerly West-Ward Pharmaceutical Corporation) (2021):
  2. "Product Information. Halfan (halofantrine)." GlaxoSmithKline (2003):
  3. Nosten F, ter Kuile FO, Luxemburger C, et al. "Cardiac effects of antimalarial treatment with halofantrine." Lancet 341 (1993): 1054-6
  4. "Sudden death in a traveler following halofantrine administration--Togo, 2000." MMWR Morb Mortal Wkly Rep 50 (2001): 169-70, 179
  5. Abernethy DR, Wesche DL, Barbey JT, et al. "Stereoselective halofantrine disposition and effect: concentration-related QTc prolongation." Br J Clin Pharmacol 51 (2001): 231-7
  6. Darpo B "Spectrum of drugs prolonging QT interval and the incidence of torsades de pointes." Eur Heart J Suppl 3(Suppl K) (2001): K70-80
View all 6 references

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Drug and food interactions

Major

halofantrine food

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

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Moderate

mefloquine food

Applies to: Lariam (mefloquine)

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of mefloquine. The proposed mechanism is increased drug solubility in the presence of food. In 20 healthy volunteers, administration of a single 750 mg oral dose of mefloquine 30 minutes following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of mefloquine by 73% and 40%, respectively, compared to administration in the fasting state. The Cmax and AUC of the carboxylic acid metabolite were also increased by 35% and 33%, respectively, compared to fasting. In addition, the time to reach peak plasma concentration (Tmax) of mefloquine was significantly shorter after food intake (17 hours) than in the fasting state (36 hours). There was no difference in the elimination half-life of mefloquine and metabolite, or the Tmax for the metabolite.

MANAGEMENT: To ensure maximal oral absorption, mefloquine should be administered immediately after a meal with at least 8 ounces of water.

References

  1. "Product Information. Mefloquine Hydrochloride (mefloquine)." Hikma USA (formerly West-Ward Pharmaceutical Corporation) (2021):
  2. Schmidt LE, Dalhoff K "Food-drug interactions." Drugs 62 (2002): 1481-502

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antimalarials

Therapeutic duplication

The recommended maximum number of medicines in the 'antimalarials' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antimalarials' category:

  • halofantrine
  • Lariam (mefloquine)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

See also

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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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