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Drug Interactions between fluoxetine and Orap

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

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Interactions between your drugs

Major

FLUoxetine pimozide

Applies to: fluoxetine and Orap (pimozide)

CONTRAINDICATED: Coadministration with fluoxetine may significantly increase the plasma concentrations of pimozide. The proposed mechanism is fluoxetine inhibition of the metabolism of pimozide via CYP450 2D6 and 3A4. Although the interaction has not been formally studied with fluoxetine, data exist for paroxetine, a drug with similar CYP450 inhibition characteristics. In a controlled study of healthy volunteers, pretreatment with immediate-release paroxetine (titrated up to 60 mg/day) increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of pimozide (2 mg single oral dose) by an average of 62% and 151%, respectively, compared to administration of pimozide alone. 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. In addition, case reports suggest that concurrent administration of fluoxetine and pimozide may be associated with mental status changes and adverse cardiovascular effects. The mechanism of interaction has not been determined but may involve additive pharmacodynamic effects and/or fluoxetine inhibition of pimozide metabolism. In one case report, a young woman receiving pimozide for obsessive delusional thoughts became stuporous and complained of inability to think clearly following the addition of fluoxetine. She also had hypersalivation while receiving the combination. In another case, an elderly patient treated with pimozide developed severe bradycardia approximately one week after the addition of fluoxetine. Decreases in pulse also occurred during titration of the pimozide dose, but they were more significant with the combination of fluoxetine and pimozide. In other reports, use of selective serotonin reuptake inhibitors in combination with neuroleptics or other agents with antidopaminergic effect have resulted in increased extrapyramidal symptoms.

MANAGEMENT: Given the narrow therapeutic index of pimozide and its known ability to prolong the QT interval, concomitant use of pimozide and fluoxetine is considered contraindicated. Due to the long half-life of fluoxetine and its metabolite norfluoxetine, the risk of an interaction may exist for an extended period (up to several weeks) after discontinuation of fluoxetine.

References

  1. Stein MH "Tardive dyskinesia in a patient taking haloperidol and fluoxetine." Am J Psychiatry 148 (1991): 683
  2. Tate JL "Extrapyramidal symptoms in a patient taking haloperidol and fluoxetine." Am J Psychiatry 146 (1989): 399-400
  3. Ketai R "Interaction between fluoxetine and neuroleptics." Am J Psychiatry 150 (1993): 836-7
  4. Ahmed I, Dagincourt PG, Miller LG, Shader RI "Possible interaction between fluoxetine and pimozide causing sinus bradycardia." Can J Psychiatry 38 (1993): 62-3
  5. Lock JD, Gwirtsman HE, Targ EF "Possible adverse drug interactions between fluoxetine and other psychotropics." J Clin Psychopharmacol 10 (1990): 383-4
  6. "Product Information. Prozac (fluoxetine)." Dista Products Company PROD (2001):
  7. Nicholson SD "Extra pyramidal side effects associated with paroxetine." West Engl Med J 107 (1992): 90-1
  8. "Product Information. Paxil (paroxetine)." GlaxoSmithKline PROD (2001):
  9. Dsouza DC, Bennett A, Abidargham A, Krystal JH "Precipitation of a psychoneuromotor syndrome by fluoxetine in a haloperidol-treated schizophrenic patient." J Clin Psychopharmacol 14 (1994): 361-3
  10. Hansen-Grant S, Silk KR, Guthrie S "Fluoxetine-pimozide interaction." Am J Psychiatry 150 (1993): 1751-2
  11. Palop V, Jimenez MJ, Catalan C, MartinezMir I "Acute dystonia associated with fluvoxamine-metoclopramide." Ann Pharmacother 33 (1999): 382
  12. Ozdemir V, Naranjo CA, Herrmann N, Reed K, Sellers EM, Kalow W "Paroxetine potentiates the central nervous system side effects of perphenazine: contribution of cytochrome P4502D6 inhibition in vivo." Clin Pharmacol Ther 62 (1997): 334-47
  13. Horrigan JP, Barnhill LJ "Paroxetine-pimozide drug interaction." J Am Acad Child Adolesc Psychiatry 33 (1994): 1060-1
View all 13 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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Moderate

FLUoxetine food

Applies to: fluoxetine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
View all 4 references

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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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