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Drug Interactions between doxepin and Mellaril

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

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Interactions between your drugs

Major

doxepin thioridazine

Applies to: doxepin and Mellaril (thioridazine)

CONTRAINDICATED: Coadministration of thioridazine with another phenothiazine or a tricyclic antidepressant (TCA) may result in elevated plasma concentrations of both drugs. Most phenothiazines and TCAs have been found to undergo metabolism by CYP450 2D6, thus competitive inhibition of the enzyme may occur when more than one of these agents are administered. The possibility of an increased risk of serious adverse effects such as central nervous system depression, hypotension, and arrhythmia should be considered. In addition, these agents individually can cause prolongation of the QT interval, thus concomitant administration may result in elevated risk of ventricular arrhythmias including ventricular tachycardia and torsade de pointes.

MANAGEMENT: The use of thioridazine with drugs that can inhibit CYP450 2D6 and/or prolong the QT interval is considered contraindicated.

References

  1. Loga S, Curry S, Lader M "Interaction of chlorpromazine and nortriptyline in patients with schizophrenia." Clin Pharmacokinet 6 (1981): 454-62
  2. Veith RC, Bloom V, Bielski R, Friedel RO "ECG effects of comparable plasma concentrations of desipramine and amitriptyline." J Clin Psychopharmacol 2 (1982): 394-8
  3. Christensen P, Thomsen HY, Pedersen OL, et al. "Cardiovascular effects of amitriptyline in the treatment of elderly depressed patients." Psychopharmacology (Berl) 87 (1985): 212-5
  4. Rudorfer MV, Young RC "Desipramine: cardiovascular effects and plasma levels." Am J Psychiatry 137 (1980): 984-6
  5. Nelson JC, Jatlow PI, Bock J, Quinlan DM, Bowes MB "Major adverse reactions during desipramine treatment." Arch Gen Psychiatry 39 (1982): 1055-61
  6. Carpenter P, Gobel FL, Hulsing DJ "Desipramine cardiac toxicity." Minn Med 65 (1982): 231-4
  7. Brosen K, Zeugin T, Meyer UA "Role of P450IID6, the target of the sparteine-debrisoquin oxidation polymorphism, in the metabolism of imipramine." Clin Pharmacol Ther 49 (1991): 609-17
  8. Luchins DJ "Review of clinical and animal studies comparing the cardiovascular effects of doxepin and other tricyclic antidepressants." Am J Psychiatry 140 (1983): 1006-9
  9. Burrows GD, Vohra J, Hunt D, Sloman JG, Scoggins BA, Davies B "Cardiac effects of different tricyclic antidepressant drugs." Br J Psychiatry 129 (1976): 335-41
  10. Linnoila M, Jobson KO, Gilliam JH, Paine RL "Effects of doxepin on blood pressure and heart rate in patients with primary major affective disorder ." J Clin Psychopharmacol 2 (1982): 433-4
  11. Strasberg B, Coelho A, Welch W, Swiryn S, Bauernfeind R, Rosen K "Doxepin induced torsade de pointes." Pacing Clin Electrophysiol 5 (1982): 873-7
  12. Bock JL, Nelson JC, Gray S, Jatlow PI "Desipramine hydroxylation: variability and effect of antipsychotic drugs." Clin Pharmacol Ther 33 (1983): 322-8
  13. Gram LF, Overo KF "Drug interaction: inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man." Br Med J 1 (1972): 463-5
  14. El-Yousef MK, Manier DH "Tricyclic antidepressants and phenothiazines." JAMA 229 (1974): 1419
  15. Hirschowitz J, Bennett JA, Zemlan FP, Garver DL "Thioridazine effect on desipramine plasma levels." J Clin Psychopharmacol 3 (1983): 376-9
  16. Vandel S, Sandoz M, Vandel B, Bonin B, Allers G, Volmat R "Biotransformation of amitriptyline in man: interaction with phenothiazines." Neuropsychobiology 15 (1986): 15-9
  17. Kantor SJ, Glassman AH, Bigger JT, Jr Perel JM, Giardina EV "The cardiac effects of therapeutic plasma concentrations of imipramine." Am J Psychiatry 135 (1978): 534-8
  18. Ramanathan KB, Davidson C "Cardiac arrhythmia and imipramine therapy." Br Med J 1 (1975): 661-2
  19. Bluhm RE, Wilkinson GR, Shelton R, Branch RA "Genetically determined drug-metabolizing activity and desipramine- associated cardiotoxicity: a case report." Clin Pharmacol Ther 53 (1993): 89-95
  20. Van Sweden B "Rebound antidepressant cardiac arrhythmia." Biol Psychiatry 24 (1988): 363-4
  21. Faravelli C, Brat A, Marchetti G, Franchi F, Padeletti L, Michelucci A, Pastorino A "Cardiac effects of clomipramine treatment. ECG and left ventricular systolic time intervals." Neuropsychobiology 9 (1983): 113-8
  22. Fletcher GF, Kazamias TM "Cardiotoxic effects of Mellaril: conduction disturbances and supraventricular arrhythmias." Am Heart J 78 (1969): 135-8
  23. Kumar BB "Letter: Acute hypotension from thioridazine." JAMA 234 (1975): 1321
  24. Siris SG, Cooper TB, Rifkin AE, Brenner R, Lieberman JA "Plasma imipramine concentrations in patients receiving concomitant fluphenazine decanoate." Am J Psychiatry 139 (1982): 104-6
  25. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation PROD (2001):
  26. Hartigan-Go K, Bateman DN, Nyberg G, Martensson E, Thomas SHL "Concentration-related pharmacodynamic effects of thioridazine and its metabolites in humans." Clin Pharmacol Ther 60 (1996): 543-53
  27. Maynard GL, Soni P "Thioridazine interferences with imipramine metabolism and measurement." Ther Drug Monit 18 (1996): 729-31
  28. Glassman AH, Bigger JT Jr "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry 158 (2001): 1774-82
View all 28 references

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Drug and food interactions

Moderate

doxepin food

Applies to: doxepin

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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Moderate

thioridazine food

Applies to: Mellaril (thioridazine)

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.

References

  1. Lutz EG "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA 236 (1976): 2422-3
  2. Freed E "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust 2 (1981): 44-5

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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

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