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Drug Interactions between aspirin / diphenhydramine / phenylpropanolamine and Polycitra-K

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

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Interactions between your drugs

Major

diphenhydrAMINE potassium citrate

Applies to: aspirin / diphenhydramine / phenylpropanolamine and Polycitra-K (citric acid / potassium citrate)

CONTRAINDICATED: The following interaction does not apply to all products containing potassium citrate. It is applicable to certain oral solid formulations of potassium citrate used primarily for potassium supplementation, and the prescriber should consult the individual product labeling for more specific information and guidance.

Concomitant use of agents with anticholinergic properties (e.g., antihistamines, antispasmodics, neuroleptics, phenothiazines, skeletal muscle relaxants, tricyclic antidepressants, the class IA antiarrhythmic disopyramide) may potentiate the risk of upper gastrointestinal injury associated with oral solid formulations of potassium citrate. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents, thereby creating a high localized concentration of potassium ions in the region of a dissolving tablet or capsule and increasing the contact time with GI mucosa. Solid formulations of potassium chloride have been associated with upper GI bleeding and small bowel ulceration, stenosis, perforation, and obstruction. Deaths have been reported rarely. In clinical studies, short-term coadministration of wax-matrix or microencapsulated formulations of potassium chloride and potassium citrate at high dosages in combination with an anticholinergic agent such as glycopyrrolate resulted in more frequent and more serious endoscopic lesions than potassium therapy alone. However, the lesions were not accompanied by bleeding or epigastric symptoms. Some investigators have suggested a higher risk of upper GI lesions with wax-matrix than microencapsulated formulations, although existing data are limited and conflicting.

MANAGEMENT: The use of oral solid formulations of potassium citrate is considered contraindicated in patients receiving agents with anticholinergic properties at sufficient doses to exert anticholinergic effects. A liquid formulation of potassium citrate should be considered. Patients prescribed a solid oral formulation should be advised to discontinue potassium therapy and contact their physician if they experience potential symptoms of upper GI injury such as severe vomiting, abdominal pain, distention, and gastrointestinal bleeding.

References

  1. Lambert JR, Newman A "Ulceration and stricture of the esophagus due to oral potassium chloride (slow release tablet) therapy." Am J Gastroenterol 73 (1980): 508-11
  2. Farquharson-Roberts MA, Giddings AE, Nunn AJ "Perforation of small bowel due to slow release potassium chloride (slow-K)." Br Med J 3 (1975): 206
  3. Wynn V "Potassium chloride and bowel ulceration." Br Med J 5477 (1965): 1546
  4. McMahon FG, Ryan JR, Akdamar K, Ertan A "Effect of potassium chloride supplements on upper gastrointestinal mucosa." Clin Pharmacol Ther 35 (1984): 852-5
  5. McMahon FG, Ryan JR, Akdamar K, Ertan A "Upper gastrointestinal lesions after potassium chloride supplements: a controlled clinical trial." Lancet 2 (1982): 1059-61
  6. Leijonmarck CE, Raf L "Gastrointestinal lesions and potassium chloride supplements." Lancet 1 (1985): 56-7
  7. Lofgren RP, Rothe PR, Carlson GJ "Jejunal perforation associated with slow-release potassium chloride therapy." South Med J 75 (1982): 1154-5
  8. Leijonmarck CE, Raf L "Ulceration of the small intestine due to slow-release potassium chloride tablets." Acta Chir Scand 151 (1985): 273-8
  9. Weiss SM, Rutenberg HL, Paskin DL, Zaren HA "Gut lesions due to slow-release KCI tablets." N Engl J Med 296 (1977): 111-2
  10. "Product Information. K-Dur (potassium chloride)." Schering Corporation PROD (2001):
  11. "Product Information. Urocit-K (potassium citrate)." Mission Pharmacal Company PROD
  12. Heffernan SJ, Murphy JJ "Ulceration of small intestine and slow-release potassium tablets." Br Med J 2 (1975): 746
View all 12 references

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Moderate

aspirin potassium citrate

Applies to: aspirin / diphenhydramine / phenylpropanolamine and Polycitra-K (citric acid / potassium citrate)

MONITOR: Agents that cause urinary alkalinization can reduce serum salicylate concentrations in patients receiving anti-inflammatory dosages of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to increased urinary pH, resulting in increased renal salicylate clearance especially above urine pH of 7. This interaction is sometimes exploited in the treatment of salicylate toxicity.

MANAGEMENT: Patients treated chronically with urinary alkalinizers and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

References

  1. Berg KJ "Acute acetylsalicylic acid poisoning: treatment with forced alkaline diuresis and diuretics." Eur J Clin Pharmacol 12 (1977): 111-6
  2. Prescott LF, Balali-Mood M, Critchley JA, Johnstone AF, Proudfoot AT "Diuresis or urinary alkalinisation for salicylate poisoning?" Br Med J (Clin Res Ed) 285 (1982): 1383-6
  3. Balali-Mood M, Prescott LF "Failure of alkaline diuresis to enhance diflunisal elimination." Br J Clin Pharmacol 10 (1980): 163-5
  4. Berg KJ "Acute effects of acetylsalicylic acid in patients with chronic renal insufficiency." Eur J Clin Pharmacol 11 (1977): 111-6
  5. Brouwers JRBJ, Desmet PAGM "Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs." Clin Pharmacokinet 27 (1994): 462-85
View all 5 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

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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