Drug Interaction Report
2 potential interactions and/or warnings found for the following 2 drugs:
- dacomitinib
- pimozide
Interactions between your drugs
pimozide dacomitinib
Applies to: pimozide, dacomitinib
CONTRAINDICATED: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations of pimozide, which is partially metabolized by the isoenzyme. In a controlled study of healthy volunteers, administration of pimozide (2 mg single dose) with the potent inhibitor paroxetine (60 mg daily) resulted in mean increases of 62% and 151% in pimozide peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to pimozide given alone. Quinidine, another potent inhibitor of CYP450 2D6, has been shown in vitro to also inhibit the metabolism of pimozide. 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: Due to the narrow therapeutic index of pimozide, the manufacturers consider its use with potent CYP450 2D6 inhibitors to be contraindicated.
References (6)
- (2001) "Product Information. Paxil (paroxetine)." GlaxoSmithKline
- "Product Information. Orap (pimozide)." Gate Pharmaceuticals
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
- Cerner Multum, Inc. "Australian Product Information."
Drug and food interactions
pimozide food
Applies to: 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 (2)
- "Product Information. Orap (pimozide)." Gate Pharmaceuticals
- Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
Therapeutic duplication warnings
No duplication 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.
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
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