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Drug Interactions between desipramine and Prozac

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

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Interactions between your drugs

Major

desipramine FLUoxetine

Applies to: desipramine and Prozac (fluoxetine)

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 Pharmacologic response and plasma TCA levels should be monitored more closely whenever fluoxetine is added to or withdrawn from therapy in patients stabilized on their existing antidepressant regimen, and the TCA dosage adjusted as necessary.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 "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 (1991): 533-6
  2. Bergstrom RF, Peyton AL, Lemberger L "Quantification and mechanism of the fluoxetine and tricyclic antidepressant interaction." Clin Pharmacol Ther 51 (1992): 239-48
  3. Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8
  4. Bell IR, Cole JO "Fluoxetine induces elevation of desipramine level and exacerbation of geriatric nonpsychotic depression." J Clin Psychopharmacol 8 (1988): 447-8
  5. Aranow AB, Hudson JI, Pope HG, et al. "Elevated antidepressant plasma levels after addition of fluoxetine." Am J Psychiatry 146 (1989): 911-3
  6. Preskorn SH, Beber JH, Faul JC, Hirschfeld RM "Serious adverse effects of combining fluoxetine and tricyclic antidepressants." Am J Psychiatry 147 (1990): 532
  7. Vandel S, Bertschy G, Bonin B, et al. "Tricyclic antidepressant plasma levels after fluoxetine." Neuropsychobiology 25 (1992): 202-7
  8. Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13
  9. Downs JM, Dahmer SK "Fluoxetine and elevated plasma levels of tricyclic antidepressants." Am J Psychiatry 147 (1990): 1251
  10. Schraml F, Benedetti G, Hoyle K, Clayton A "Fluoxetine and nortriptyline combination therapy." Am J Psychiatry 146 (1989): 1636-7
  11. Downs JM, Downs AD "Effect of fluoxetine on metabolism of tricyclic antidepressants in the lungs." Am J Psychiatry 146 (1989): 814-5
  12. Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol 10 (1990): 213-7
  13. Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics." J Clin Psychopharmacol 10 (1990): 48-50
  14. Vaughan DA "Interaction of fluoxetine with tricyclic antidepressants." Am J Psychiatry 145 (1988): 1478
  15. Wilens TE, Biederman J, Baldessarini RJ, McDermott SP, Puopolo PR, Flood JG "Fluoxetine inhibits desipramine metabolism." Arch Gen Psychiatry 49 (1992): 752
  16. DeMaso DR, Hunter TA "Combining fluoxetine with desipramine." J Am Acad Child Adolesc Psychiatry 29 (1990): 151
  17. Westermeyer J "Fluoxetine-induced tricyclic toxicity: extent and duration." J Clin Pharmacol 31 (1991): 388-92
  18. von Ammon Cavanaugh S "Drug-drug interactions of fluoxetine with tricyclics." Psychosomatics 31 (1990): 273-6
  19. Gillman PK "Fluoxetine (prozac)." Med J Aust 159 (1993): 492
  20. Preskorn SH, Alderman J, Chung M, Harrison W, Messig M, Harris S "Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine." J Clin Psychopharmacol 14 (1994): 90-8
  21. von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, Duan SX, Harmatz JS, Shader RI "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 (1994): 1278-83
  22. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals PROD (2001):
  23. Popli AP, Baldessarini RJ, Cole JO "Interactions of serotonin reuptake inhibitors with tricyclic antidepressants." Arch Gen Psychiatry 51 (1994): 666-7
  24. Crewe HK, Lennard MS, Tucker GT, Woods FR, Haddock RE "The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes." Br J Clin Pharmacol 34 (1992): 262-5
  25. Elyazigi A, Chaleby K, Gad A, Raines DA "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 (1995): 17-21
  26. Sternbach H "Fluoxetine-clomipramine interaction." J Clin Psychiatry 56 (1995): 171-2
  27. Harvey AT, Preskorn SH "Interactions of serotonin reuptake inhibitors with tricyclic antidepressants." Arch Gen Psychiatry 52 (1995): 783-4
  28. Taylor D "Selective serotonin reuptake inhibitors and tricyclic antidepressants in combination - interactions and therapeutic uses." Br J Psychiatry 167 (1995): 575-80
  29. Riesenman C "Antidepressant drug interactions and the cytochrome p450 system: a critical appraisal." Pharmacotherapy 15 (1995): s84-99
  30. Fischer P "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol 15 (1995): 440-2
  31. Corkeron MA "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust 163 (1995): 481-2
  32. Leroi I, Walentynowicz MA "Fluoxetine-imipramine interaction." Can J Psychiatry 41 (1996): 318-9
  33. Preskorn SH, Baker B "Fatality associated with combined fluoxetine-amitryptyline therapy." JAMA 277 (1997): 1682
  34. Paul KL, Bhatara VS "Anticholinergic delerium possibly associated with protriptyline and fluoxetine." Ann Pharmacother 31 (1997): 1260-1
  35. Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763
  36. Mathew NT, Tietjen GE, Lucker C "Serotonin syndrome complicating migraine pharmacotherapy." Cephalalgia 16 (1996): 323-7
  37. Nijhawan PK, Katz G, Winter S "Psychiatric illness and the serotonin syndrome: an emerging adverse drug effect leading to intensive care unit admission." Crit Care Med 24 (1996): 1086-9
  38. Laird LK "Issues in the monopharmacotherapy and polypharmacotherapy of obsessive-compulsive disorder." Psychopharmacol Bull 32 (1996): 569-78
  39. Ereshefsky L, Riesemman C, Lam YW "Antidepressant drug interactions and the cytochrome P450 system. The role of cytochrome P450 2D6." Clin Pharmacokinet 29(Suppl 1) (1995): 10-8; discussion 18-9
  40. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  41. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
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View all 42 references

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Drug and food interactions

Moderate

FLUoxetine food

Applies to: Prozac (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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Moderate

desipramine food

Applies to: desipramine

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

References

  1. Dorian P, Sellers EM, Reed KL, et al. "Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction." Eur J Clin Pharmacol 25 (1983): 325-31
  2. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R "Biotransformation of amitriptyline in alcoholic depressive patients." Eur J Clin Pharmacol 24 (1983): 615-21
  4. Ciraulo DA, Barnhill JG, Jaffe JH "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther 43 (1988): 509-18
  5. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther 17 (1975): 515-22
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF "Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls." J Stud Alcohol 51 (1990): 366-72
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA "Imipramine disposition in alcoholics." J Clin Psychopharmacol 2 (1982): 2-7
View all 7 references

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antidepressants

Therapeutic duplication

The recommended maximum number of medicines in the 'antidepressants' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antidepressants' category:

  • desipramine
  • Prozac (fluoxetine)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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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