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Drug Interactions between glycerol phenylbutyrate and pimozide

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

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Interactions between your drugs

Moderate

pimozide glycerol phenylbutyrate

Applies to: pimozide and glycerol phenylbutyrate

MONITOR: Coadministration with glycerol phenylbutyrate may decrease the systemic exposure to and therapeutic efficacy of drugs that are substrates of CYP450 3A4. Glycerol phenylbutyrate, its active moiety phenylbutyrate, and active metabolite phenylacetic acid are considered weak CYP450 3A4 inducers in vivo. In healthy subjects, coadministration of glycerol phenylbutyrate (4.4 g orally three times daily for 3 days) with oral midazolam, a sensitive CYP450 3A4 substrate, decreased the peak plasma concentration (Cmax) and systemic exposure (AUC) of midazolam of approximately 25% and 32%, respectively, and increased the mean Cmax and AUC of its metabolite 1-hydroxy midazolam, by 28% and 58%, respectively, compared to administration of midazolam alone. The clinical significance has not been established.

MANAGEMENT: Concomitant use of glycerol phenylbutyrate with sensitive CYP450 3A4 substrates (e.g., oral midazolam) or CYP450 3A4 substrates with a narrow therapeutic index (e.g., alfentanil, oral contraceptives, quinidine, and cyclosporine) should be done with caution and monitoring for reduced efficacy. Dosage adjustment as well as clinical and laboratory monitoring may be appropriate whenever glycerol phenylbutyrate is added to or withdrawn from therapy.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2013) "Product Information. Ravicti (glycerol phenylbutyrate)." Hyperion Therapeutics Inc

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Drug and food interactions

Major

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

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

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