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Drug Interactions between cimetidine and Mellaril-S

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

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Interactions between your drugs

Major

cimetidine thioridazine

Applies to: cimetidine and Mellaril-S (thioridazine)

CONTRAINDICATED: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations and adverse effects of thioridazine and its two active metabolites, mesoridazine and sulforidazine, all of which are substrates of the isoenzyme. A study in 19 healthy male patients reviewed thioridazine metabolism in 6 slow and 13 rapid hydroxylators of debrisoquin (the rate of which is believed to be dependent upon the level of CYP450 2D6 activity). A single oral dose of thioridazine (25 mg) produced a 2.4-fold higher peak plasma concentration (Cmax) and a 4.5-fold higher systemic exposure (AUC) for thioridazine in the slow hydroxylators, which is predicted to be similar to what would be seen in patients on CYP450 2D6 inhibitors. Additionally, significant increases (up to severalfold) have been observed during coadministration with fluvoxamine, propranolol, and pindolol in pharmacokinetic studies, although these reductions in clearance may be via other currently unknown mechanisms. The use of thioridazine has been associated with dose-related prolongation of the QT interval, thus elevated plasma levels of the drug may potentiate the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes as well as cardiac arrest and sudden death. Several cases of torsade de pointes have been reported.

MANAGEMENT: The use of thioridazine with fluvoxamine, propranolol, pindolol and/or drugs that inhibit CYP450 2D6 is considered contraindicated. Depending on the elimination half-life of these drugs, a considerable waiting period may be appropriate following their discontinuation before thioridazine is initiated. For example, the manufacturer of fluoxetine recommends that thioridazine not be administered within 5 weeks after discontinuing fluoxetine because of the drug's long half-life. In addition, the prolonged duration of CYP450 2D6 inhibition by the moderate CYP450 2D6 inhibitor rolapitant of at least 28 days after its administration should also be taken into account.

References

  1. Silver JM, Yudofsky SC, Kogan M, Katz BL "Elevation of thioridazine plasma levels by propranolol." Am J Psychiatry 143 (1986): 1290-2
  2. Greendyke RM, Kanter DR "Plasma propranolol levels and their effect on plasma thioridazine and haloperidol concentrations." J Clin Psychopharmacol 7 (1987): 178-82
  3. Greendyke RM, Gulya A "Effect of pindolol administration on serum levels of thioridazine, haloperidol, phenytoin, and phenobarbital." J Clin Psychiatry 49 (1988): 105-7
  4. Abernethy DR, Greenblatt DJ, Steel K, Shader RI "Impairment of hepatic drug oxidation by propoxyphene." Ann Intern Med 97 (1982): 223-4
  5. "Product Information. Prozac (fluoxetine)." Dista Products Company PROD (2001):
  6. Fletcher GF, Kazamias TM "Cardiotoxic effects of Mellaril: conduction disturbances and supraventricular arrhythmias." Am Heart J 78 (1969): 135-8
  7. Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9
  8. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation PROD (2001):
  9. Thomas M, Maconochie JG, Fletcher E "The dilemma of the prolonged QT interval in early drug studies." Br J Clin Pharmacol 41 (1996): 77-81
  10. 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
  11. Carrillo JA, Ramos SI, Herraiz AG, Llerena A, Agundez JAG, Berecz R, Duran M, Benitez J "Pharmacokinetic interaction of fluvoxamine and thioridazine in schizophrenic patients." J Clin Psychopharmacol 19 (1999): 494-9
  12. Glassman AH, Bigger JT Jr "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry 158 (2001): 1774-82
  13. "Product Information. Varubi (rolapitant)." Tesaro Inc. (2015):
  14. "Product Information. Thioridazine Hydrochloride (thioridazine)." Mylan Institutional (formerly UDL Laboratories) (2019):
View all 14 references

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Drug and food interactions

Moderate

thioridazine food

Applies to: Mellaril-S (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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Minor

cimetidine food

Applies to: cimetidine

Concurrent use of cimetidine and ethanol may result in increased ethanol concentrations. The mechanism appears to be due to inhibition of gastric alcohol dehydrogenase by cimetidine, leading to increased bioavailability of the alcohol and inhibition of hepatic metabolism of alcohol. The clinical significance of this interaction is limited. More importantly, patients requiring cimetidine for gastrointestinal disease should be counseled to avoid alcohol to prevent worsening of their disease. The other H-2 receptor antagonists appear to have minimal effects on the concentrations of alcohol.

References

  1. Feely J, Wood AJ "Effects of cimetidine on the elimination and actions of ethanol." JAMA 247 (1982): 2819-21
  2. Hansten PD "Effects of H2-receptor antagonists on blood alcohol levels." JAMA 267 (1992): 2469

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Minor

cimetidine food

Applies to: cimetidine

Caffeine effects may be increased in patients also taking cimetidine. The mechanism may be due to decreased caffeine metabolism induced by cimetidine. Although adequate clinical data are lacking, a reduction in dose or elimination of caffeine may be needed if excess CNS stimulation is observed.

References

  1. "Product Information. Tagamet (cimetidine)." SmithKline Beecham PROD (2001):
  2. Broughton LJ, Rodgers HJ "Decreased systenuc clearance of caffeine due to cimetidine." Br J Clin Pharmacol 12 (1981): 155-9

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Minor

cimetidine food

Applies to: cimetidine

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

References

  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol 38 (1990): 165-9

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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