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Drug Interactions between fluoxetine and risperidone

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

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Interactions between your drugs

Moderate

FLUoxetine risperiDONE

Applies to: fluoxetine and risperidone

MONITOR: Coadministration with fluoxetine may increase the plasma concentrations of certain neuroleptic agents and potentiate the risk of extrapyramidal adverse effects. The proposed mechanism is inhibition of CYP450 2D6 metabolism by fluoxetine and its active metabolite, norfluoxetine. In 10 psychiatric patients stabilized on risperidone therapy (4 to 6 mg/day), the addition of fluoxetine (20 mg/day) led to a mean 4-fold increase in plasma risperidone concentrations and a 75% increase in levels of active moiety (i.e. sum of the concentrations of risperidone and its active 9-hydroxy metabolite). One patient developed severe akathisia and two developed Parkinsonian symptoms within the first two weeks. In contrast, mean plasma concentrations of haloperidol were elevated by just 20% following the addition of fluoxetine (20 mg/day for 7 to 10 days) in eight psychotic patients stabilized on haloperidol, and extrapyramidal side effects did not increase appreciably. However, haloperidol has been implicated clinically in various case reports, as has the phenothiazine fluphenazine. Some believe that a pharmacodynamic interaction may be partially responsible, as fluoxetine alone has been associated with extrapyramidal symptoms, possibly due to serotonergic inhibition of nigrostriatal dopaminergic pathways.

MANAGEMENT: Caution is recommended if fluoxetine is prescribed with phenothiazines or other neuroleptic agents that are thought to be metabolized by CYP450 2D6. Plasma neuroleptic levels and pharmacologic effects should be closely monitored and the dosage(s) adjusted accordingly, particularly following initiation or discontinuation of fluoxetine in patients who are stabilized on their neuroleptic regimen. Patients should be advised to contact their physician if they develop extrapyramidal symptoms such as tremor, shuffling gait, drooling, a mask-like face, tongue stiffness, muscle spasms or rigidity, and involuntary movements. Due to the long half-life of fluoxetine and norfluoxetine, the risk of an interaction may exist for an extended period (up to several weeks) after discontinuation of fluoxetine.

References

  1. Stein MH (1991) "Tardive dyskinesia in a patient taking haloperidol and fluoxetine." Am J Psychiatry, 148, p. 683
  2. Tate JL (1989) "Extrapyramidal symptoms in a patient taking haloperidol and fluoxetine." Am J Psychiatry, 146, p. 399-400
  3. Goff DC, Midha KK, Brotman AW, Waites M, Baldessarini RJ (1991) "Elevation of plasma concentrations of haloperidol after the addition of fluoxetine." Am J Psychiatry, 148, p. 790-2
  4. (1989) "Fluoxetine and extrapyramidal side effects." Am J Psychiatry, 146, p. 1352-3
  5. Ketai R (1993) "Interaction between fluoxetine and neuroleptics." Am J Psychiatry, 150, p. 836-7
  6. Baldessarini RJ, Marsh E (1990) "Fluoxetine and side effects." Arch Gen Psychiatry, 47, p. 191-2
  7. Ciraulo DA, Shader RI (1990) "Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics." J Clin Psychopharmacol, 10, p. 48-50
  8. Lock JD, Gwirtsman HE, Targ EF (1990) "Possible adverse drug interactions between fluoxetine and other psychotropics." J Clin Psychopharmacol, 10, p. 383-4
  9. Dsouza DC, Bennett A, Abidargham A, Krystal JH (1994) "Precipitation of a psychoneuromotor syndrome by fluoxetine in a haloperidol-treated schizophrenic patient." J Clin Psychopharmacol, 14, p. 361-3
  10. Avenoso A, Spina E, Campo G, Facciola G, Ferlito M, Zuccaro P, Perucca E, Caputi AP (1997) "Interaction between fluoxetine and haloperidol: Pharmacokinetic and clinical implications." Pharmacol Res, 35, p. 335-9
  11. Tyndale RF, Kalow W, Inaba T (1991) "Oxidation of reduced haloperidol to haloperidol: involvement of human P450IID6 (sparteine/debrisoquine monooxygenase)." Br J Clin Pharmacol, 31, p. 655-60
  12. Bork JA, Rogers T, Wedlund PJ, deLeon J (1999) "A pilot study on risperidone metabolism: The role of cytochromes P450 2D6 and 3A." J Clin Psychiatry, 60, p. 469-76
  13. Spina E, Avenoso A, Scordo MG, et al. (2002) "Inhibition of Risperidone Metabolism by Fluoxetine in Patients With Schizophrenia: A Clinically Relevant Pharmacokinetic Drug Interaction." J Clin Psychopharmacol, 22, p. 419-423
View all 13 references

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Drug and food interactions

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

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Moderate

risperiDONE food

Applies to: risperidone

GENERALLY AVOID: Risperidone oral solution is not compatible with either tea or cola. In addition, alcohol may potentiate some of the pharmacologic effects of risperidone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Risperidone oral solution should not be mixed with tea or cola. It may be taken with water, coffee, orange juice, or lowfat milk. Patients should also be advised to avoid consumption of alcohol.

References

  1. (2001) "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals

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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.

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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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