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Drug Interactions between nirmatrelvir / ritonavir and pimozide

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

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Interactions between your drugs

Major

pimozide ritonavir

Applies to: pimozide and nirmatrelvir / ritonavir

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

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 (2)
  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
Moderate

ritonavir food

Applies to: nirmatrelvir / ritonavir

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References (1)
  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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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