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Drug Interaction Report

3 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Major

diphenhydrAMINE potassium citrate

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

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Drug and food interactions

Major

acetaminophen food

Applies to: acetaminophen / diphenhydramine

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

References

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA (1985) "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med, 145, p. 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA (1986) "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA, 255, p. 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB (1986) "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med, 104, p. 399-404
  4. Thummel KE, Slattery JT, Nelson SD (1988) "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther, 245, p. 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL (1980) "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA, 244, p. 251-3
  6. Kartsonis A, Reddy KR, Schiff ER (1986) "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med, 105, p. 138-9
  7. Prescott LF, Critchley JA (1983) "Drug interactions affecting analgesic toxicity." Am J Med, 75, p. 113-6
  8. (2002) "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical
  9. Whitcomb DC, Block GD (1994) "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA, 272, p. 1845-50
  10. Bonkovsky HL (1995) "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA, 274, p. 301
  11. Nelson EB, Temple AR (1995) "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA, 274, p. 301
  12. Zimmerman HJ, Maddrey WC (1995) "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology, 22, p. 767-73
View all 12 references

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Moderate

diphenhydrAMINE food

Applies to: acetaminophen / diphenhydramine

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

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Therapeutic duplication warnings

No duplication 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.


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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.

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Further information

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