Skip to main content

Drug Interactions between aspirin / diphenhydramine / phenylpropanolamine and thioridazine

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

diphenhydrAMINE thioridazine

Applies to: aspirin / diphenhydramine / phenylpropanolamine and 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 (1986) "Elevation of thioridazine plasma levels by propranolol." Am J Psychiatry, 143, p. 1290-2
  2. Greendyke RM, Kanter DR (1987) "Plasma propranolol levels and their effect on plasma thioridazine and haloperidol concentrations." J Clin Psychopharmacol, 7, p. 178-82
  3. Greendyke RM, Gulya A (1988) "Effect of pindolol administration on serum levels of thioridazine, haloperidol, phenytoin, and phenobarbital." J Clin Psychiatry, 49, p. 105-7
  4. Abernethy DR, Greenblatt DJ, Steel K, Shader RI (1982) "Impairment of hepatic drug oxidation by propoxyphene." Ann Intern Med, 97, p. 223-4
  5. (2001) "Product Information. Prozac (fluoxetine)." Dista Products Company
  6. Fletcher GF, Kazamias TM (1969) "Cardiotoxic effects of Mellaril: conduction disturbances and supraventricular arrhythmias." Am Heart J, 78, p. 135-8
  7. Markowitz JS, Wells BG, Carson WH (1995) "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother, 29, p. 603-9
  8. (2001) "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation
  9. Thomas M, Maconochie JG, Fletcher E (1996) "The dilemma of the prolonged QT interval in early drug studies." Br J Clin Pharmacol, 41, p. 77-81
  10. Hartigan-Go K, Bateman DN, Nyberg G, Martensson E, Thomas SHL (1996) "Concentration-related pharmacodynamic effects of thioridazine and its metabolites in humans." Clin Pharmacol Ther, 60, p. 543-53
  11. Carrillo JA, Ramos SI, Herraiz AG, Llerena A, Agundez JAG, Berecz R, Duran M, Benitez J (1999) "Pharmacokinetic interaction of fluvoxamine and thioridazine in schizophrenic patients." J Clin Psychopharmacol, 19, p. 494-9
  12. Glassman AH, Bigger JT Jr (2001) "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry, 158, p. 1774-82
  13. (2015) "Product Information. Varubi (rolapitant)." Tesaro Inc.
  14. (2019) "Product Information. Thioridazine Hydrochloride (thioridazine)." Mylan Institutional (formerly UDL Laboratories)
View all 14 references

Switch to consumer interaction data

Moderate

thioridazine phenylpropanolamine

Applies to: thioridazine and aspirin / diphenhydramine / phenylpropanolamine

GENERALLY AVOID: Phenothiazines may antagonize the pharmacologic effects of amphetamine, amphetamine derivatives, and other centrally-acting sympathomimetic agents (i.e., CNS stimulants). Conversely, these agents may diminish the neuroleptic efficacy of phenothiazines. The exact mechanism of interaction is unknown but may involve opposing effects on dopaminergic activity. Several clinical studies have demonstrated the reduction or lack of effect of amphetamines on weight loss in obese psychiatric patients treated with chlorpromazine and other neuroleptic agents. In one of these studies, dextroamphetamine also had no effect on sleep patterns. As for the reverse interaction, it is uncertain whether CNS stimulants actually antagonize the neuroleptic effect of phenothiazines, since CNS stimulants alone have been reported to cause or aggravate preexisting psychotic symptoms. Finally, it is conceivable that, because of their sympathomimetic effects, CNS stimulants may also potentiate the arrhythmogenicity of phenothiazines. A case of fatal ventricular arrhythmia was reported in a patient treated chronically with thioridazine who ingested a single capsule containing phenylpropanolamine 50 mg and chlorpheniramine 4 mg. However, a causal relationship was not established.

MANAGEMENT: Amphetamine, amphetamine derivatives, and other CNS stimulants should generally not be used, particularly for weight reduction, in patients treated with phenothiazines.

References

  1. Reid AA (1964) "Pharmacological antagonism between chlorpromazine and phenmetrazine in mental hospital patients." Med J Aust, 1, p. 187-8
  2. Sletten IW, Ognjanov V, Menendez S, Sundland D, El-Toumi A (1967) "Weight reduction with chlorphentermine and phenmetrazine in obese psychiatric patients during chlorpromazine therapy." Curr Ther Res Clin Exp, 9, p. 570-5
  3. Chouinard G, Ghadirian AM, Jones BD (1978) "Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac*C capsule." Can Med Assoc J, 119, p. 729-31
  4. Casey JF, Hollister LE, Klett CJ, Lasky JJ, Caffey EM (1961) "Combined drug therapy of chronic schizophrenics." Am J Psychiatry, 177, p. 997
  5. Modell W, Hussar AE (1965) "Failure of dextroamphetamine sulfate to incluence eating and sleeping patterns in obese schizophrenic patients." JAMA, 193, p. 275-8
  6. Angrist B, Lee HK, Gershon S (1974) "The antagonism of amphetamine-induced symptomatology by a neuroleptic." Am J Psychiatry, 131, p. 817-9
  7. Cornelius JR, Soloff PH, Reynolds CF, 3d (1984) "Paranoia, homicidal behavior, and seizures associated with phenylpropanolamine." Am J Psychiatry, 141, p. 120-1
  8. Achor MB, Extein I (1981) "Diet aids, mania, and affective illness" Am J Psychiatry, 138, p. 392
  9. Schaffer CB, Pauli MW (1980) "Psychotic reaction caused by proprietary oral diet agents." Am J Psychiatry, 137, p. 1256-7
  10. Grieger TA, Clayton AH, Goyer PF (1990) "Affective disorder following use of phenylpropanolamine" Am J Psychiatry, 147, p. 367-8
  11. Dietz AJ, Jr (1981) "Amphetamine-like reactions to phenylpropanolamine." JAMA, 245, p. 601-2
  12. Norvenius G, Widerlov E, Lonnerholm G (1979) "Phenylpropanolamine and mental disturbances" Lancet, 2, p. 1367-8
  13. Mueller SM (1983) "Neurologic complications of phenylpropanolamine use." Neurology, 33, p. 650-2
  14. Lake CR, Tenglin R, Chernow B, Holloway HC (1983) "Psychomotor stimulant-induced mania in a genetically predisposed patient: a review of the literature and report of a case." J Clin Psychopharmacol, 3, p. 97-100
  15. Lake CR (1991) "Manic psychosis after coffee and phenylpropanolamine." Biol Psychiatry, 30, p. 401-4
  16. Lambert MT (1987) "Paranoid psychoses after abuse of proprietary cold remedies." Br J Psychiatry, 151:, p. 548-50
  17. Wharton BK (1970) "Nasal decongestants and paranoid psychosis." Br J Psychiatry, 117, p. 439-40
  18. Dewsnap P, Libby G (1992) "A case of affective psychosis after routine use of proprietary cold remedy containing phenylpropanolamine" Hum Exp Toxicol, 11, p. 295-6
  19. Finton CK, Barton M, Chernow B (1982) "Possible adverse effects of phenylpropanolamine (diet pills) on sympathetic nervous system function--caveat emptor!" Mil Med, 147, p. 1072
  20. Stroe AE, Hall J, Amin F (1995) "Psychotic episode related to phenylpropanolamine and amantadine in a healthy female." Gen Hosp Psychiatry, 17, p. 457-8
  21. Marshall RD, Douglas CJ (1994) "Phenylpropanolamine-induced psychosis: potential predisposing factors." Gen Hosp Psychiatry, 16, p. 358-60
  22. (2001) "Product Information. Fastin (phentermine)." SmithKline Beecham
  23. (2001) "Product Information. Cylert (pemoline)." Abbott Pharmaceutical
  24. (2001) "Product Information. Ritalin (methylphenidate)." Novartis Pharmaceuticals
  25. (2001) "Product Information. Desoxyn (methamphetamine)." Abbott Pharmaceutical
  26. (2001) "Product Information. Dexedrine (dextroamphetamine)." SmithKline Beecham
  27. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  28. (2001) "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn
  29. (2001) "Product Information. Prelu-2 (phendimetrazine)." Boehringer-Ingelheim
  30. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  31. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  32. Markowitz JS, Patrick KS (2001) "Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder." Clin Pharmacokinet, 40, p. 753-72
  33. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  34. (2007) "Product Information. Vyvanse (lisdexamfetamine)." Shire US Inc
View all 34 references

Switch to consumer interaction data

Drug and food interactions

Moderate

phenylpropanolamine food

Applies to: aspirin / diphenhydramine / phenylpropanolamine

GENERALLY AVOID: Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

MANAGEMENT: Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease. Patients should be counselled 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. Mendelson J, Jones RT, Upton R, Jacob P 3rd (1995) "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther, 57, p. 559-68
  2. (2001) "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn
  3. (2012) "Product Information. Suprenza (phentermine)." Akrimax Pharmaceuticals

Switch to consumer interaction data

Moderate

aspirin food

Applies to: aspirin / diphenhydramine / phenylpropanolamine

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

Switch to consumer interaction data

Moderate

diphenhydrAMINE food

Applies to: aspirin / diphenhydramine / phenylpropanolamine

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M (1973) "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol, 6, p. 107-12

Switch to consumer interaction data

Moderate

thioridazine food

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

Switch to consumer interaction data

Moderate

phenylpropanolamine food

Applies to: aspirin / diphenhydramine / phenylpropanolamine

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
View all 7 references

Switch to consumer interaction data

Minor

aspirin food

Applies to: aspirin / diphenhydramine / phenylpropanolamine

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6

Switch to consumer interaction data

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

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer