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Drug Interactions between aspirin / dipyridamole and Diamox

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

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Interactions between your drugs

Major

acetaZOLAMIDE aspirin

Applies to: Diamox (acetazolamide) and aspirin / dipyridamole

GENERALLY AVOID: The combination of large doses of salicylates and oral carbonic anhydrase inhibitors (CAI) may rarely result in severe metabolic acidosis and/or salicylate toxicity. The mechanism is unknown but may involve salicylate-induced displacement of CAIs from plasma protein-binding sites and reduced renal clearance, or CAI-induced plasma pH changes resulting in increased amounts of unionised salicylates entering the CNS. Coma and death have been reported. Although this has not been reported with ocular CAIs, the clinician should consider the possibility of an interaction with these agents, also.

MANAGEMENT: In general, concomitant use of antirheumatic doses of salicylates and oral CAIs is not recommended. If coadministration is necessary, careful monitoring of the patient's mental status and acid base balance is strongly recommended. Patients should be advised to promptly notify their physicians if they experience symptoms such as lethargy, tinnitus, confusion, nausea, vomiting, or hyperventilation.

References

  1. Sweeney KR, Chapron DJ, Kramer PA "Effect of salicylate on serum protein binding and red blood cell uptake of acetazolamide in vitro." J Pharm Sci 77 (1988): 751-6
  2. Favre L, Vallotton MB "Relationship of renal prostaglandins to three diuretics." Prostaglandins Leukot Med 14 (1984): 313-9
  3. Cowan RA, Hartnell GG, Lowdell CP, Baird IM, Leak AM "Metabolic acidosis induced by carbonic anhydrase inhibitors and salicylates in patients with normal renal function." Br Med J (Clin Res Ed) 289 (1984): 347-8
  4. Sweeney KR, Chapron DJ, Brandt JL, Gomolin IH, Feig PU, Kramer PA "Toxic interaction between acetazolamide and salicylate: case reports and a pharmacokinetic explanation." Clin Pharmacol Ther 40 (1986): 518-24
  5. Anderson CJ, Kaufman PL, Sturm RJ "Toxicity of combined therapy with carbonic anhydrase inhibitors and aspirin." Am J Ophthalmol 86 (1978): 516-9
  6. Sweeney KR, Chapron DJ, Antal EJ, Kramer PA "Differential effects of flurbiprofen and aspirin on acetazolamide disposition in humans." Br J Clin Pharmacol 27 (1989): 866-9
  7. Rousseau P, Fuentevilla-Clifton A "Acetazolamide and salicylate interaction in the elderly: a case report." J Am Geriatr Soc 41 (1993): 868-9
  8. "Product Information. Diamox (acetazolamide)." Lederle Laboratories PROD (2001):
  9. "Product Information. Azopt (brinzolamide ophthalmic)." Alcon Laboratories Inc PROD (2001):
  10. "Product Information. Trusopt (dorzolamide ophthalmic)." Merck & Co., Inc PROD (2001):
  11. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  12. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  13. Cerner Multum, Inc. "Australian Product Information." O 0
View all 13 references

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Drug and food interactions

Moderate

dipyridamole food

Applies to: aspirin / dipyridamole

ADJUST DOSING INTERVAL: Caffeine and other xanthine derivatives (e.g., theophylline) are nonspecific, competitive antagonists of adenosine receptors. As such, they may interfere with the vasodilating effect of dipyridamole, an adenosine receptor agonist. In studies of healthy volunteers, caffeine has been shown to reduce the hemodynamic response (i.e., heart rate increases, vasodilation, blood pressure changes) to dipyridamole infusions, and both caffeine and theophylline have been reported to cause false-negative results in myocardial scintigraphy tests using dipyridamole.

MANAGEMENT: Patients should avoid consumption of caffeine-containing products for at least 24 hours prior to administration of dipyridamole for myocardial perfusion imaging.

References

  1. Smits P, Aengevaeren WR, Corstens FH, Thien T "Caffeine reduces dipyridamole-induced myocardial ischemia." J Nucl Med 30 (1989): 1723-6
  2. "Product Information. Persantine (dipyridamole)." Boehringer-Ingelheim PROD (2002):
  3. Ranhosky A, Kempthorne-Rawson J, the Intravenous Dipyridamole Thallium Imaging Study Group "The safety of intravenous dipyridamole thallium myocardial perfusion imaging." Circulation 81 (1990): 1205-9

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Moderate

aspirin food

Applies to: aspirin / dipyridamole

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

dipyridamole food

Applies to: aspirin / dipyridamole

ADJUST DOSING INTERVAL: Methylxanthines (e.g., caffeine, theophylline) are nonspecific, competitive antagonists of adenosine receptors. As such, they may interfere with the pharmacologic effects of adenosine and other adenosine receptor agonists such as dipyridamole and regadenoson. There have been case reports of patients receiving theophylline who required higher than normal dosages of adenosine for the treatment of paroxysmal supraventricular tachycardia. In studies of healthy volunteers, caffeine and theophylline have been shown to reduce the cardiovascular response to adenosine infusions (i.e., heart rate increases, vasodilation, blood pressure changes), and theophylline has also been shown to attenuate adenosine-induced respiratory effects and chest pain/discomfort. Similarly, caffeine has been found to reduce the hemodynamic response to dipyridamole, and both caffeine and theophylline have been reported to cause false-negative results in myocardial scintigraphy tests using dipyridamole. In a placebo-controlled study that assessed the effects of oral caffeine on regadenoson-induced increase in coronary flow reserve (CFR), healthy subjects who took caffeine 200 mg orally two hours prior to regadenoson administration exhibited a median CFR that was 92% that of subjects who took placebo. The study was done using positron emission tomography with radiolabeled water.

MANAGEMENT: Clinicians should be aware that adenosine and other adenosine receptor agonists may be less effective in the presence of methylxanthines. Methylxanthines including caffeine should be withheld for 12 to 24 hours (or five half-lives) prior to administration of adenosine receptor agonists for myocardial perfusion imaging. However, parenteral aminophylline should be readily available for treating severe or persistent adverse reactions to adenosine receptor agonists such as bronchospasm or chest pain.

References

  1. Conti CR "Adenosine: clinical pharmacology and applications." Clin Cardiol 14 (1991): 91-3
  2. Smits P, Aengevaeren WR, Corstens FH, Thien T "Caffeine reduces dipyridamole-induced myocardial ischemia." J Nucl Med 30 (1989): 1723-6
  3. Smits P, Schouten J, Thien T "Respiratory stimulant effects of adenosine in man after caffeine and enprofylline." Br J Clin Pharmacol 24 (1987): 816-9
  4. Minton NA, Henry JA "Pharmacodynamic interactions between infused adenosine and oral theophylline." Hum Exp Toxicol 10 (1991): 411-8
  5. "Product Information. Persantine (dipyridamole)." Boehringer-Ingelheim PROD (2002):
  6. "Product Information. Adenocard (adenosine)." Fujisawa PROD (2001):
  7. Ranhosky A, Kempthorne-Rawson J, the Intravenous Dipyridamole Thallium Imaging Study Group "The safety of intravenous dipyridamole thallium myocardial perfusion imaging." Circulation 81 (1990): 1205-9
  8. "Product Information. Adenoscan (adenosine)." Fujisawa (2001):
  9. "Product Information. Lexiscan (regadenoson)." Astellas Pharma US, Inc (2008):
View all 9 references

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Minor

aspirin food

Applies to: aspirin / dipyridamole

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.