Sunday, November 10, 2013

Does enteric coating aspirin change efficacy or adverse effects?

Bleeding risk with anticoagulant and antiplatelet medications is something that we struggle with on a regular basis.  Should we fully anticoagulate a patient with atrial fibrillation who is falling?  Should we continue the aspirin and clopidogrel even though it’s X number of months since their stents? 

One question that has been raised is the effect of the enteric coating on aspirin tablets and if that shifts the risk:benefit balance.  This week’s pearl will highlight some changes that occur with aspirin when the enteric coated dosage form is used.

NSAIDs, including aspirin, and infection with H. pylori are the most common cause of ulcer disease.  The gastric damage induced by NSAIDs is due to two mechanisms:
(1) the direct irritation of the gastric epithelium by the medication and
(2) systemic inhibition of prostaglandin synthesis

While the acidic property of aspirin may promote the initial injury, the systemic effects likely play a larger role in preventing the mucosa from repairing itself.1  Drug companies have attempted to limit the effect of the direct irritation of the gastric epithelium by formulating acidic drugs with an enteric coating.  The purpose of an enteric coating is to delay the release of the drug until the dosage form has passed through the stomach.  By this design, enteric coating behaves as a delayed release formulation.  To meet the FDA standards for enteric coating, a drug has to first be stable for 2 hours in an acidic environment (as in only release a minimal amount of drug) and then the drug must be completely released when moved to a pH of 4.5-7.5.2 


As far as effect of enteric coating on the efficacy of aspirin, it has been shown to delay the absorption of aspirin and therefore reduce the antithrombotic effect in the acute setting.  Therefore, in settings where a rapid antithrombotic effect is desired (such as ACS) enteric coated aspirin should not be substituted for immediate release formulations and if it is the only formulation available, it should be crushed or chewed.  For chronic administration, there are conflicting studies on the antiplatelet effects of enteric coated aspirin.  Some studies have shown reduced platelet responsiveness (a tricky surrogate) to aspirin in patients taking chronic enteric coated tablets owing possibly to incomplete absorption.  Other studies, however, show equal AUC curves and urinary salicylate levels between formulations.  There are no studies testing enteric coated versus nonenteric coated aspirin for cardiovascular endpoints and no guidelines recommend one type of aspirin over the other for chronic dosing.


Enteric coated aspirin seems theoretically promising in terms of improving tolerability and side effect.  Studies have shown reduced erosions on endoscopy in patients taking enteric coated aspirin but no effect on upper gastrointestinal bleeding.3 This is again likely due to the fact that gastrointestinal bleeding is a result of the systemic cyclooxygenase inhibiting effects of NSAIDs.  Dyspepsia may be improved with the enteric coated formulation or by taking the aspirin with food.

Here’s one last point about aspirin efficacy.  Taking other NSAIDs like ibuprofen or naproxen can actually competitively interfere with aspirin from binding to the cyclooxygenase enzyme, inhibiting aspirin’s action.  Patients should be counseled not to take these medications at the same time.  Waiting at least a half hour after immediate-release aspirin or taking the ibuprofen 8 hours before aspirin should avoid the interaction.  For enteric coated aspirin, no separation in dosing can be made due to the delayed absorption and lack of data. An FDA warning is available for this interaction.4

Take home points:

  • For acute antithrombotic effects – use immediate release aspirin or crush enteric coated aspirin (otherwise absorption delayed for hours)
  • For chronic use – enteric coating may decrease effectiveness of aspirin but there are no studies with cardiovascular endpoints
  • For side effects – enteric coating can reduce dyspepsia and erosions on EGD but not gastrointestinal bleeding
  • Avoid regular use of other NSAIDs with aspirin because of competition to the binding site
1.  Berardi RR, Fugit RV. Chapter 40. Peptic Ulcer Disease. In: Wells BG, ed.Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; 2011. Accessed November 10, 2013.
2.  Guidance for Industry SUPAC-MR: Modified Release Solid Oral Dosage Forms.  FDA.  Available at:
3.  Kelly JP, Kaufman DW, Jurgelon JM, Sheehan J, Koff RS, Shapiro S.  Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product.  Lancet. 1996;348(9039):1413.

4.  Information for Healthcare Professionals: Concomitant Use of Ibuprofen and Aspirin.  FDA.  Available at:

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