NSAIDs or Aspirin + Proton pump inhibitors - Drug Interactions

The antiplatelet activity and pharmacokinetics of aspirin donot appear to be affected by omeprazole. There was no clinicallyrelevant pharmacokinetic interaction between omeprazole anddiclofenac,enteric-coated ketoprofen, naproxen or piroxicam, orbetween pantoprazole and diclofenac or naproxen, or betweenesomeprazole and naproxen or rofecoxib.

In a preliminary study in 11 healthy subjects, omeprazole 20mg daily for 2 days reduced serum levels of salicylic acid metabolite of aspirin at 30 and 90 minutes after a single 650mg dose of aspirin by 40 % and 52%, respectively (See reference number 1). However, another study in 14 healthy subjects given omeprazole 20 mg daily for 4 days with a final dose one hour before a single 125mg dose of aspirin found that omeprazole did not significantly affect plasma levels of either aspirin or salicylic acid. Omeprazole also did not affect antiplatelet effects of aspirin (See reference number 2). Similarly, omeprazole had no effect on bioavailability of aspirin (uncoated or entericcoated tablets) in another study, although it increased rate of absorption of aspirin from enteric-coated tablets (See reference number 3).

A single 105mg dose of diclofenac potassium suspension (Flogan) was given to 13 healthy subjects while fasting and after gastric acid secretion blockade with omeprazole. The pharmacokinetics of diclofenac were not changed to a clinically relevant extent by omeprazole (See reference number 4). Similarly, omeprazole 20mg daily given with diclofenac 50mg twice daily for one week had no effect on pharmacokinetics of either drug in 24 healthy subjects (See reference number 5).

Neither drug affected pharmacokinetics of other (See reference number 6)

There were no significant changes in pharmacokinetics of entericcoated ketoprofen, given with or without omeprazole, although a trend towards higher plasma concentrations with omeprazole was noted, indicating possibility of increased drug release in stomach in presence of an elevated pH (See reference number 7).

Naproxen 250mg twice daily given to healthy subjects with omeprazole 20 mg daily,(See reference number 5)pantoprazole 40mg daily,(See reference number 8) or esomeprazole 40mg daily(See reference number 9)for one week had no effect on pharmacokinetics of either naproxen or proton pump inhibitor

The pharmacokinetics of pantoprazole 40mg orally daily for 8 days was not altered to a clinically relevant extent by a single 5-mg/kg oral dose of phenazone given on day 8 of study. Pantoprazole did not affect pharmacokinetics of phenazone (See reference number 10)

Omeprazole 20 mg daily given to 24 healthy subjects with piroxicam 10mg daily for one week had no effect on pharmacokinetics of either drug (See reference number 5)

12.5 mg daily for one week had no effect on pharmacokinetics of either drug apart from a slight increase in maximum level and AUC of rofecoxib, which was not thought to be clinically relevant (See reference number 9).

Data from animal studies suggest that absorption and thus effects of aspirin and NSAIDs can be reduced by omeprazole and H2-receptor antagonists via a pH dependent mechanism (See reference number 11,12). However, note that clinical studies have not found H2-receptor antagonists to have any important effect on pharmacokinetics of aspirin or NSAIDs, see NSAIDs or Aspirin + H2-receptor antagonists interaction. It has been suggested that reducing gastric acidity with omeprazole results in earlier disruption of entericcoated tablets, and an increased absorption rate (See reference number 3).

The interaction between aspirin and omeprazole is not established. The balance of evidence suggests that omeprazole is unlikely to have an important effect on pharmacokinetics and efficacy of aspirin. However, because of uncertainty generated by animal and preliminary clinical data,(See reference number 1,11,12) it would be of benefit to confirm this in further studies (See reference number 2,13).

No clinically significant pharmacokinetic interactions have been identified between any of other NSAIDs and PPIs cited here, and no special precautions are needed during concurrent use. For mention that valdecoxib raises plasma levels of omeprazole see NSAIDs; Parecoxib + Miscellaneous interaction. Note that omeprazole and other proton pump inhibitors are widely used in management of gastrointestinal complications of aspirin and NSAIDs.

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