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Drug Interactions between halofantrine and Quin-Release

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

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Interactions between your drugs

Major

quiNIDine halofantrine

Applies to: Quin-Release (quinidine) and halofantrine

CONTRAINDICATED: Halofantrine can cause dose-related prolongation of the QT interval at recommended therapeutic doses. QTc interval prolongation and death have been reported during combination use of halofantrine and mefloquine. 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.

MANAGEMENT: Coadministration of halofantrine with other drugs that can prolong the QT interval is considered contraindicated. 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. Giao PT, de Vries PJ "Pharmacokinetic interactions of antimalarial agents." Clin Pharmacokinet 40 (2001): 343-73
  3. "Product Information. Halfan (halofantrine)." GlaxoSmithKline (2003):
  4. Nosten F, ter Kuile FO, Luxemburger C, et al. "Cardiac effects of antimalarial treatment with halofantrine." Lancet 341 (1993): 1054-6
  5. "Sudden death in a traveler following halofantrine administration--Togo, 2000." MMWR Morb Mortal Wkly Rep 50 (2001): 169-70, 179
  6. 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
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  8. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  9. Cerner Multum, Inc. "Australian Product Information." O 0
View all 9 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

quiNIDine food

Applies to: Quin-Release (quinidine)

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

References

  1. Ace LN, Jaffe JM, Kunka RL "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos 4 (1983): 183-90
  2. Min DI, Ku YM, Geraets DR, Lee HC "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol 36 (1996): 469-76
  3. Ha HR, Chen J, Leuenberger PM, Freiburghaus AU, Follah F "In vitro inhibition of midazolam and quinidine metabolism by flavonoids." Eur J Clin Pharmacol 48 (1995): 367-71
  4. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
View all 4 references

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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.

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

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