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Drug Interactions between Norpramin and Paxil

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

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Interactions between your drugs

Major

desipramine PARoxetine

Applies to: Norpramin (desipramine) and Paxil (paroxetine)

GENERALLY AVOID: Coadministration with paroxetine may significantly increase the plasma concentrations of some tricyclic antidepressants (TCAs). The proposed mechanism is paroxetine inhibition of CYP450 2D6, the isoenzyme responsible for the metabolic clearance of many antidepressant and psychotropic drugs. Several-fold increases in plasma levels and decreases in metabolic clearance have been reported for desipramine and nortriptyline, while smaller changes have been reported for amitriptyline and imipramine, presumably because other CYP450 isoenzymes are also involved in their metabolism. Pharmacodynamically, the combination of paroxetine (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 paroxetine (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 Pharmacologic response and plasma TCA levels should be monitored more closely whenever paroxetine is added to or withdrawn from therapy in patients stabilized on their existing antidepressant regimen, and the TCA dosage adjusted as necessary.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).

References

  1. Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13
  2. Brosen K, Hansen JG, Nielsen KK, Sindrup SH, Gram LF "Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine." Eur J Clin Pharmacol 44 (1993): 349-55
  3. Popli AP, Baldessarini RJ, Cole JO "Interactions of serotonin reuptake inhibitors with tricyclic antidepressants." Arch Gen Psychiatry 51 (1994): 666-7
  4. 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
  5. Vonmoltke LL, Greenblatt DJ, Court MH, Duan SX, Harmatz JS, Shader RI "Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: comparison with other selective serotonin reuptake inhibitor antidepressants." J Clin Psychopharmacol 15 (1995): 125-31
  6. Taylor D "Selective serotonin reuptake inhibitors and tricyclic antidepressants in combination - interactions and therapeutic uses." Br J Psychiatry 167 (1995): 575-80
  7. Riesenman C "Antidepressant drug interactions and the cytochrome p450 system: a critical appraisal." Pharmacotherapy 15 (1995): s84-99
  8. Fischer P "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol 15 (1995): 440-2
  9. Corkeron MA "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust 163 (1995): 481-2
  10. Albers LJ, Reist C, Helmeste D, Vu R, Tang SW "Paroxetine shifts imipramine metabolism." Psychiatry Res 59 (1996): 189-96
  11. Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT "Cytochromes p450 mediating the n-demethylation of amitriptyline." Br J Clin Pharmacol 43 (1997): 137-44
  12. Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763
  13. Mathew NT, Tietjen GE, Lucker C "Serotonin syndrome complicating migraine pharmacotherapy." Cephalalgia 16 (1996): 323-7
  14. Leucht S, Hackl HJ, Steimer W, Angersbach D, Zimmer R "Effect of adjunctive paroxetine on serum levels and side-effects of tricyclic antidepressants in depressive inpatients." Psychopharmacology 147 (2000): 378-83
  15. 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
  16. Venkatakrishnan K, Schmider J, Harmatz JS, et al. "Relative contribution of CYP3A to amitriptyline clearance in humans: in vitro and in vivo studies." J Clin Pharmacol 41 (2001): 1043-54
  17. Laine K, Tybring G, Hartter S, et al. "Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test." Clin Pharmacol Ther 70 (2001): 327-35
  18. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  19. Yang TJ, Krausz KW, Sai Y, Gonzalez FJ, Gelbon HV "Eight inhibitory monoclonal antibodies define the role of individual P-450S in human liver microsomal diazepam, 7-ethoxycoumarin, and imipramine metabolism." Drug Metab Dispos 27 (1999): 102-9
View all 19 references

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Drug and food interactions

Moderate

PARoxetine food

Applies to: Paxil (paroxetine)

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: Norpramin (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:

  • Norpramin (desipramine)
  • Paxil (paroxetine)

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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