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Drug Interactions between halofantrine and Lumakras

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

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Interactions between your drugs

Moderate

halofantrine sotorasib

Applies to: halofantrine and Lumakras (sotorasib)

MONITOR: Coadministration with sotorasib may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is increased metabolic clearance due to induction of CYP450 3A4 by sotorasib. When midazolam, a sensitive CYP450 3A4 substrate, was coadministered with sotorasib, midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 48% and 53%, respectively. These results suggest moderate induction of CYP450 3A4 by sotorasib.

MANAGEMENT: Caution is advised when sotorasib is used concomitantly with drugs that are substrates of CYP450 3A4, particularly sensitive substrates or those with a narrow therapeutic range. The prescribing information recommends avoiding coadministration of sotorasib with CYP450 3A4 substrates for which minimal concentration changes may lead to therapeutic failure. If coadministration is required, dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever sotorasib is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration of a moderate CYP450 3A4 inducer like sotorasib and for any dosage adjustments that may be required.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2021) "Product Information. Lumakras (sotorasib)." Amgen USA

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 (4)
  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
Minor

sotorasib food

Applies to: Lumakras (sotorasib)

Food does not appear to have a clinically significant effect on the oral bioavailability of sotorasib. When a 960 mg dose of sotorasib was administered to study patients with a high-fat, high-calorie meal (approximately 800 to 1000 calories; 150, 250, and 500 to 600 calories from protein, carbohydrate, and fat, respectively), sotorasib peak plasma concentration (Cmax) did not change while systemic exposure (AUC 0-24 hours) increased by 25% compared to administration under fasted conditions. Sotorasib can be administered with or without food at approximately the same time each day.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2021) "Product Information. Lumakras (sotorasib)." Amgen USA

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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