Drug Interaction Report

Acetazolamide and Aspirin Rectal: Interaction Details

AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Aspirin Rectal

Aspirin
+

Acetazolamide

Diamox® Sequels®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Jul 11, 2026
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 46 documented Acetazolamide interactions, 36 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
delayed
Evidence
theoretical
Severity
Major

What happens

Salicylate toxicity (vomiting, tachycardia, hyperpnea, mental confusion) or acetaZOLAMIDE toxicity (fatigue, lethargy, somnolence, confusion, hyperchloremic metabolic acidosis)

Interaction Deep Dive

Concomitant administration of aspirin with acetaZOLAMIDE may increase the risk of anorexia, tachypnea, lethargy, metabolic acidosis, and may result in coma and death. Caution is advised for patients receiving concomitant high-dose aspirin and acetaZOLAMIDE123. If used concurrently (especially in patients with renal dysfunction or receiving large doses of aspirin), monitor for salicylate toxicity. The concurrent use of acetaZOLAMIDE and aspirin may result in altered binding and/or altered renal excretion of acetaZOLAMIDE. Decreased elimination of acetaZOLAMIDE may result in acidosis and thus increased penetration of aspirin into the central nervous system 4.

Why it happens (mechanism)

Increased acetaZOLAMIDE concentration and shift of salicylates from plasma into tissue

Literature reports

3 reports — tap to read

a) Concomitant aspirin and acetaZOLAMIDE therapy has been reported to result in a shift of salicylates from plasma into tissue and possible exacerbation of salicylate intoxication. The clinical significance of this interaction has not been established; however, acetaZOLAMIDE should be avoided in patients with salicylate intoxication 5.

b) Salicylates increase serum acetaZOLAMIDE concentrations; symptoms of acetaZOLAMIDE intoxication can result, such as fatigue, lethargy, somnolence, confusion, and hyperchloremic metabolic acidosis 4.

c) In a small pharmacokinetic, crossover study, found that aspirin increased the unbound fraction of acetaZOLAMIDE by threefold. Renal clearance of the unbound acetaZOLAMIDE was also decreased, which may be consistent with an increased risk of acetaZOLAMIDE intoxication in this situation 6.

Common questions

Can I take Acetazolamide and Aspirin Rectal together?

Salicylate toxicity (vomiting, tachycardia, hyperpnea, mental confusion) or acetaZOLAMIDE toxicity (fatigue, lethargy, somnolence, confusion, hyperchloremic metabolic acidosis) Always confirm with your pharmacist or prescriber before making any change.

How serious is the Acetazolamide and Aspirin Rectal interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "delayed". Effects tend to build up gradually over days to weeks.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Acetazolamide or Aspirin Rectal need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there a safer alternative to one of these medications for me?

References (6)

  1. Product Information: Acetazolamide oral tablets, acetazolamide oral tablets. Avet Pharmaceuticals Inc (per DailyMed), East Brunswick, NJ, 2022. DailyMed
  2. Product Information: Acetazolamide oral extended-release capsules, acetazolamide oral extended-release capsules. Micro Labs USA Inc (per DailyMed), Somerset, NJ, 2022. DailyMed
  3. Product Information: Acetazolamide intravenous injection, acetazolamide intravenous injection. X-Gen Pharmaceuticals DJB, Inc (per DailyMed), Big Flats, NY, 2020. DailyMed
  4. Sweeney KR, Chapron DJ, Brandt JL, et al: Toxic interaction between acetazolamide and salicylate: case reports and a pharmacokinetic explanation. Clin Pharmacol Ther 1986; 40:518-524. PubMed
  5. Hill JB: Experimental salicylate poisoning: Observation on effects of altering blood pH on tissue and plasma salicylate concentrations. Pediatrics 1971; 47:658.
  6. Sweeney KR, Chapron DJ, Antal EJ, et al: Differential effects of flurbiprofen and aspirin on acetazolamide disposition in humans. Br J Clin Pharmacol 1989; 27:866-869. PubMed
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Beyond drug–drug

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.