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Drug Interactions between Excedrin Extra Strength and sulfinpyrazone

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

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Interactions between your drugs

Moderate

acetaminophen sulfinpyrazone

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine) and sulfinpyrazone

MONITOR: Sulfinpyrazone may increase the potential hepatotoxicity of acetaminophen and decrease its pharmacologic effects. The mechanism may be related to accelerated metabolism of acetaminophen with consequent increased hepatotoxic metabolites. This interaction is of greatest concern in cases of acetaminophen overdose. Data have been limited.

MANAGEMENT: Until more information is available, the use of this combination over a prolonged period of time should probably be avoided. Special dosage adjustments are not needed with normal therapeutic dosages of both agents. Monitoring for clinical and laboratory evidence of hepatotoxicity is recommended.

References

  1. Miners JO, Attwood J, Birkett DJ "Determinants of acetaminophen metabolism: effect of inducers and inhibitors of drug metabolism on acetaminophen's metabolic pathways." Clin Pharmacol Ther 35 (1984): 480-6

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Moderate

aspirin sulfinpyrazone

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine) and sulfinpyrazone

GENERALLY AVOID: Salicylates may antagonize the uricosuric effect of sulfinpyrazone. The exact mechanism of interaction is unknown, although therapeutic doses of aspirin have been shown to increase plasma clearance of sulfinpyrazone. In one study, acute pretreatment with aspirin (325 mg four times a day for 24 hours) resulted in increased plasma clearance of a single 400 mg dose of sulfinpyrazone in 5 of 6 subjects by 12% to 27% relative to administration of sulfinpyrazone alone. When sulfinpyrazone 200 mg and aspirin 325 mg were coadministered four times a day for one week, plasma clearance of sulfinpyrazone increased up to 229%. The investigators theorized that aspirin may displace sulfinpyrazone from plasma protein binding sites, resulting in a redistribution of sulfinpyrazone into peripheral compartments and increased amount of free drug for hepatic metabolism. In vitro data also suggest that sulfinpyrazone may interfere with the irreversible effects of aspirin (especially low doses) on platelets, although the clinical significance is unknown.

MANAGEMENT: Salicylates should not be used during sulfinpyrazone therapy for gouty arthritis. However, occasional small doses of salicylates are not expected to interact significantly.

References

  1. Buchanan MR, Endrenyi L, Giles AR, Rosenfeld J "The effect of aspirin on the pharmacokinetics of sulfinpyrazone in man." Thromb Res Suppl 4: (1983): 145-52
  2. "Product Information. Anturane (sulfinpyrazone)." Novartis Pharmaceuticals PROD (2001):
  3. Ali M, McDonald JW "Interference by sulfinpyrazone and salicylate of aspirin inhibition of platelet cyclooxygenase activity." Prostaglandins Med 3 (1979): 327-32

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Minor

aspirin caffeine

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine) and Excedrin Extra Strength (acetaminophen / aspirin / caffeine)

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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Drug and food interactions

Major

acetaminophen food

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine)

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

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Moderate

aspirin food

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine)

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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Minor

caffeine food

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine)

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

References

  1. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy 16 (1996): 1046-52

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Minor

aspirin food

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine)

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.


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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.