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Drug Interactions between idelalisib and Orap

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

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Interactions between your drugs

Major

pimozide idelalisib

Applies to: Orap (pimozide) and idelalisib

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of pimozide, which is partially metabolized by the isoenzyme. The use of pimozide has been associated with dose-related prolongation of the QT interval, thus elevated plasma levels of the drug may potentiate the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes as well as cardiac arrest and sudden death.

MANAGEMENT: Given the potential for serious and life-threatening adverse cardiac events associated with increased plasma levels of pimozide, concomitant use with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, conivaptan, idelalisib, nefazodone, cobicistat, delavirdine, and most protease inhibitors is considered contraindicated. Some authorities consider concomitant administration of pimozide and itraconazole to be contraindicated during and for 2 weeks after treatment with itraconazole. With respect to less potent CYP450 3A4 inhibitors, the manufacturers recommend that they also not be used with pimozide.

References

  1. "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals PROD (2002):
  2. "Product Information. Orap (pimozide)." Gate Pharmaceuticals PROD
  3. Desta Z, Kerbusch T, Flockhart DA "Effect of clarithromycin on the pharmacokinetics and pharmacodynamics of pimozide in healthy poor and extensive metabolizers of cytochrome P450 2D6 (CYP2D6)." Clin Pharmacol Ther 65 (1999): 10-20
  4. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  5. Glassman AH, Bigger JT Jr "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry 158 (2001): 1774-82
  6. Mangum EM, Graham KK "Lopinavir-Ritonavir: a new protease inhibitor." Pharmacotherapy 21 (2001): 1352-63
  7. Krahenbuhl S, Sauter B, Kupferschmidt H, Krause M, Wyss PA, Meier PJ "Case report: reversible QT prolongation with torsades de pointes in a patient with pimozide intoxication." Am J Med Sci 309 (1995): 315-6
  8. Flockhart DA, Drici MD, Kerbusch T, et al. "Studies on the mechanism of a fatal clarithromycin-pimozide interaction in a patient with tourette syndrome." J Clin Psychopharmacol 20 (2000): 317-24
  9. Cerner Multum, Inc. "Australian Product Information." O 0
View all 9 references

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Drug and food interactions

Major

pimozide food

Applies to: Orap (pimozide)

GENERALLY AVOID: Theoretically, the coadministration with grapefruit juice may increase the plasma concentrations of pimozide. The mechanism is decreased clearance of pimozide due to inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The use of pimozide alone has been associated with dose-dependent prolongation of the QT interval. Although clinical data are lacking, this interaction may result in potentiation of the proarrhythmic effect of pimozide and consequently an increased risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes. In addition, alcohol may potentiate some of the pharmacologic effects of pimozide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: The manufacturer recommends avoiding grapefruit juice (and probably grapefruits) during therapy with pimozide. Patients should also be advised to avoid or limit consumption of alcohol.

References

  1. "Product Information. Orap (pimozide)." Gate Pharmaceuticals PROD
  2. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57

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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

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

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