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Drug Interactions between aspirin / diphenhydramine / phenylpropanolamine and Prolixin Enanthate

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

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Interactions between your drugs

Moderate

diphenhydrAMINE fluPHENAZine

Applies to: aspirin / diphenhydramine / phenylpropanolamine and Prolixin Enanthate (fluphenazine)

MONITOR: Centrally-acting anticholinergic agents may antagonize the therapeutic effects of neuroleptic agents. Although these drugs have been used together clinically, the possibility of increased risk of adverse effects such as central nervous system depression and tardive dyskinesia should also be considered. In addition, excessive anticholinergic effects may occur in combination use, which can result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of anticholinergic intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. In hot weather, the risk of hyperthermia and heat stroke should be considered, as neuroleptic agents can interfere with temperature regulation in the hypothalamus while anticholinergic agents tend to inhibit peripheral sweating mechanisms.

MANAGEMENT: Caution is advised if anticholinergic agents are used with neuroleptic agents, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Prophylactic administration of anticholinergic agents is sometimes given clinically during neuroleptic therapy for drug-induced parkinsonism or extrapyramidal symptoms but may not always be appropriate. Patients prescribed this combination should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A dosage reduction in one or both drugs may be necessary if excessive adverse effects develop. During hot weather, patients should avoid prolonged sun exposure and intense physical exertion and maintain adequate fluid intake.

References

  1. Stadnyk AN, Glezos JD "Drug-induced heat stroke." Can Med Assoc J 128 (1983): 957-9
  2. Zelman S, Guillan R "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry 126 (1970): 1787-90
  3. Mann SC, Boger WP "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry 135 (1978): 1097-100
  4. Rockland L, Cooper T, Schwartz F, Weber D, Sullivan T "Effects of trihexyphenidyl on plasma chlorpromazine in young schizophrenics." Can J Psychiatry 35 (1990): 604-7
  5. Warnes H, Lehmann HE, Ban TA "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J 96 (1967): 1112-3
  6. Rivera-Calimlim L, Nasrallah H, Strauss J, Lasagna L "Clinical response and plasma levels: effect of dose, dosage schedules, and drug interactions on plasma chlorpromazine levels." Am J Psychiatry 133 (1976): 646-52
  7. Gershon S, Neubauer H, Sundland DM "Interaction between some anticholinergic agents and phenothiazines." Clin Pharmacol Ther 6 (1965): 749-56
  8. Singh MM, Kay SR "Therapeutic antagonism between anticholinergic antiparkinsonism agents and neuroleptics in schizophrenia: implications for a neuropharmacological model." Neuropsychobiology 5 (1979): 74-86
  9. Sarnquist F, Larson CP Jr "Drug-induced heat stroke." Anesthesiology 39 (1973): 348-50
  10. Johnson AL, Hollister LE, Berger PA "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry 42 (1981): 313-7
  11. Lee BS "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry 47 (1986): 571
  12. Forester D "Fatal drug-induced heat stroke." JACEP 7 (1978): 243-4
  13. Moreau A, Jones BD, Banno V "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry 31 (1986): 339-41
  14. Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm 2 (1983): 174-8
  15. Roth A, Akyol S, Nelson JC "Delirium associated with the combination of a neuroleptic, an SSRI, and benztropine." J Clin Psychiatry 55 (1994): 492-5
  16. "Product Information. Cogentin (benztropine)." Merck & Co., Inc PROD (2001):
  17. Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 75-82
  18. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories PROD (2001):
  19. Byerly MJ, Christensen RC, Evans DL "Delirium associated with a combination of sertraline, haloperidol, and benztropine." Am J Psychiatry 153 (1996): 965-6
  20. Hansen LB, Elley J, Christensen TR, Larsen NE, Naestoft J, Hvidberg EF "Plasma levels of perphenazine and its major metabolites during simultaneous treatment with anticholinergic drugs." Br J Clin Pharmacol 7 (1979): 75-80
  21. Kwok JS, Chan TY "Recurrent heat-related illnesses during antipsychotic treatment." Ann Pharmacother 39 (2005): 1940-2
View all 21 references

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Moderate

fluPHENAZine phenylpropanolamine

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

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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 "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther 57 (1995): 559-68
  2. "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn PROD (2001):
  3. "Product Information. Suprenza (phentermine)." Akrimax Pharmaceuticals (2012):

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

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

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Moderate

fluPHENAZine food

Applies to: Prolixin Enanthate (fluphenazine)

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

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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 "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet 11 (1986): 71-6

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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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