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Drug Interactions between fluoxetine and Zonalon

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

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Major

FLUoxetine doxepin topical

Applies to: fluoxetine and Zonalon (doxepin topical)

GENERALLY AVOID: Coadministration with fluoxetine may significantly increase the plasma concentrations of some tricyclic antidepressants (TCAs). The proposed mechanism is fluoxetine inhibition of CYP450 2D6, the isoenzyme responsible for the metabolic clearance of many antidepressant and psychotropic drugs. Seizures and delirium have been reported, as well as a fatality attributed to fluoxetine-induced chronic amitriptyline toxicity. Pharmacodynamically, the combination of fluoxetine (or any other selective serotonin reuptake inhibitor) and a TCA may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5HT1A receptors.

MANAGEMENT: In general, the use of fluoxetine (or other SSRIs) with TCAs should be avoided if possible, or otherwise approached with caution if potential benefit is deemed to outweigh the risk. Pharmacologic response and plasma TCA levels should be monitored more closely whenever fluoxetine is added to or withdrawn from therapy in patients stabilized on their existing antidepressant regimen, and the TCA dosage adjusted as necessary. Patients should be monitored closely for signs and symptoms of TCA toxicity (e.g., sedation, dry mouth, blurred vision, constipation, urinary retention) and/or excessive serotonergic activity (e.g., CNS irritability, altered consciousness, confusion, myoclonus, ataxia, abdominal cramping, hyperpyrexia, shivering, pupillary dilation, diaphoresis, hypertension, and tachycardia). Due to the long half-life of fluoxetine and its active metabolite, norfluoxetine, the risk of interaction may persist for several weeks after discontinuation of fluoxetine. For this reason, some authorities recommend a washout period of two to five weeks before and after treatment with fluoxetine.

References

  1. Muller N, Brockmoller J, Roots I (1991) "Extremely long plasma half-life of amitriptyline in a woman with the cytochrome P450IID6 29/29-kilobase wild-type allele: a slowly reversible interaction with fluoxetine." Ther Drug Monit, 13, p. 533-6
  2. Bergstrom RF, Peyton AL, Lemberger L (1992) "Quantification and mechanism of the fluoxetine and tricyclic antidepressant interaction." Clin Pharmacol Ther, 51, p. 239-48
  3. Nierenberg DW, Semprebon M (1993) "The central nervous system serotonin syndrome." Clin Pharmacol Ther, 53, p. 84-8
  4. Bell IR, Cole JO (1988) "Fluoxetine induces elevation of desipramine level and exacerbation of geriatric nonpsychotic depression." J Clin Psychopharmacol, 8, p. 447-8
  5. Aranow AB, Hudson JI, Pope HG, et al. (1989) "Elevated antidepressant plasma levels after addition of fluoxetine." Am J Psychiatry, 146, p. 911-3
  6. Preskorn SH, Beber JH, Faul JC, Hirschfeld RM (1990) "Serious adverse effects of combining fluoxetine and tricyclic antidepressants." Am J Psychiatry, 147, p. 532
  7. Vandel S, Bertschy G, Bonin B, et al. (1992) "Tricyclic antidepressant plasma levels after fluoxetine." Neuropsychobiology, 25, p. 202-7
  8. Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
  9. Downs JM, Dahmer SK (1990) "Fluoxetine and elevated plasma levels of tricyclic antidepressants." Am J Psychiatry, 147, p. 1251
  10. Schraml F, Benedetti G, Hoyle K, Clayton A (1989) "Fluoxetine and nortriptyline combination therapy." Am J Psychiatry, 146, p. 1636-7
  11. Downs JM, Downs AD (1989) "Effect of fluoxetine on metabolism of tricyclic antidepressants in the lungs." Am J Psychiatry, 146, p. 814-5
  12. Ciraulo DA, Shader RI (1990) "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol, 10, p. 213-7
  13. Ciraulo DA, Shader RI (1990) "Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics." J Clin Psychopharmacol, 10, p. 48-50
  14. Vaughan DA (1988) "Interaction of fluoxetine with tricyclic antidepressants." Am J Psychiatry, 145, p. 1478
  15. Wilens TE, Biederman J, Baldessarini RJ, McDermott SP, Puopolo PR, Flood JG (1992) "Fluoxetine inhibits desipramine metabolism." Arch Gen Psychiatry, 49, p. 752
  16. DeMaso DR, Hunter TA (1990) "Combining fluoxetine with desipramine." J Am Acad Child Adolesc Psychiatry, 29, p. 151
  17. Westermeyer J (1991) "Fluoxetine-induced tricyclic toxicity: extent and duration." J Clin Pharmacol, 31, p. 388-92
  18. von Ammon Cavanaugh S (1990) "Drug-drug interactions of fluoxetine with tricyclics." Psychosomatics, 31, p. 273-6
  19. Gillman PK (1993) "Fluoxetine (prozac)." Med J Aust, 159, p. 492
  20. Preskorn SH, Alderman J, Chung M, Harrison W, Messig M, Harris S (1994) "Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine." J Clin Psychopharmacol, 14, p. 90-8
  21. von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, Duan SX, Harmatz JS, Shader RI (1994) "Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants, and by quinidine and ketoconazole: a model system to predict drug interactions in vivo." J Pharmacol Exp Ther, 268, p. 1278-83
  22. (2001) "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals
  23. Popli AP, Baldessarini RJ, Cole JO (1994) "Interactions of serotonin reuptake inhibitors with tricyclic antidepressants." Arch Gen Psychiatry, 51, p. 666-7
  24. Crewe HK, Lennard MS, Tucker GT, Woods FR, Haddock RE (1992) "The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes." Br J Clin Pharmacol, 34, p. 262-5
  25. Elyazigi A, Chaleby K, Gad A, Raines DA (1995) "Steady-state kinetics of fluoxetine and amitriptyline in patients treated with a combination of these drugs as compared with those treated with amitriptyline alone." J Clin Pharmacol, 35, p. 17-21
  26. Sternbach H (1995) "Fluoxetine-clomipramine interaction." J Clin Psychiatry, 56, p. 171-2
  27. Harvey AT, Preskorn SH (1995) "Interactions of serotonin reuptake inhibitors with tricyclic antidepressants." Arch Gen Psychiatry, 52, p. 783-4
  28. Taylor D (1995) "Selective serotonin reuptake inhibitors and tricyclic antidepressants in combination - interactions and therapeutic uses." Br J Psychiatry, 167, p. 575-80
  29. Riesenman C (1995) "Antidepressant drug interactions and the cytochrome p450 system: a critical appraisal." Pharmacotherapy, 15, s84-99
  30. Fischer P (1995) "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol, 15, p. 440-2
  31. Corkeron MA (1995) "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust, 163, p. 481-2
  32. Leroi I, Walentynowicz MA (1996) "Fluoxetine-imipramine interaction." Can J Psychiatry, 41, p. 318-9
  33. Preskorn SH, Baker B (1997) "Fatality associated with combined fluoxetine-amitryptyline therapy." JAMA, 277, p. 1682
  34. Paul KL, Bhatara VS (1997) "Anticholinergic delerium possibly associated with protriptyline and fluoxetine." Ann Pharmacother, 31, p. 1260-1
  35. Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
  36. Mathew NT, Tietjen GE, Lucker C (1996) "Serotonin syndrome complicating migraine pharmacotherapy." Cephalalgia, 16, p. 323-7
  37. Nijhawan PK, Katz G, Winter S (1996) "Psychiatric illness and the serotonin syndrome: an emerging adverse drug effect leading to intensive care unit admission." Crit Care Med, 24, p. 1086-9
  38. Laird LK (1996) "Issues in the monopharmacotherapy and polypharmacotherapy of obsessive-compulsive disorder." Psychopharmacol Bull, 32, p. 569-78
  39. Ereshefsky L, Riesemman C, Lam YW (1995) "Antidepressant drug interactions and the cytochrome P450 system. The role of cytochrome P450 2D6." Clin Pharmacokinet, 29(Suppl 1), 10-8; discussion 18-9
  40. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
  41. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  42. Cerner Multum, Inc. "Australian Product Information."
View all 42 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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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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