Non-Steroidal Anti-Inflammatory Drugs and Gastroprotection with Proton Pump Inhibitors

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed agents for rheumatic disorders such as osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Despite the known association between NSAID use and gastropathy, however, only around one-third of patients at risk of NSAID-induced gastrointestinal toxicity receive adequate gastroprotection, and as many as 44% of these patients are non-adherent. We review the co-prescription of proton pump inhibitors (PPIs) for the prevention of NSAID-induced gastropathy, with a particular focus on the first fixed-dose NSAID/PPI formulation: ketoprofen/omeprazole modified-release capsules. The ketoprofen/omeprazole fixed-dose combination is available in doses of 100 mg/20 mg, 150 mg/20 mg or 200 mg/20 mg as a single capsule for once-daily administration. Ketoprofen monotherapy has been shown to be generally equivalent to other NSAIDs when used in the treatment of OA. In RA, ketoprofen has demonstrated equivalent efficacy to diclofenac, indometacin, piroxicam, aceclofenac, phenylbutazone, naproxen and flurbiprofen. Studies comparing ketoprofen with ibuprofen and sulindac in patients with RA have, in general, favoured ketoprofen. Studies in AS have generally reported similar efficacy between ketoprofen and phenylbutazone and pirprofen. Prophylaxis with omeprazole is effective for the prevention of gastroduodenal ulcers, maintenance of remission and alleviation of dyspeptic symptoms in NSAID recipients. Omeprazole is well tolerated, and adverse events are generally gastrointestinal in nature. The fixed-dose combination of ketoprofen and omeprazole has demonstrated bioequivalence to the respective monotherapies. The incidence of digestive symptoms and the need for dose reduction was reported to be lower with the combination than with its components. Ketoprofen/omeprazole modified-release capsules are the first fixed-dose NSAID/PPI formulation to be approved. This formulation ensures compliance with the gastroprotective prophylaxis, as whenever the NSAID is taken, the PPI is co-administered. Additionally, the once-daily formulation has the potential to improve adherence to anti-inflammatory therapy.

Use of NSAIDs in treating patients with arthritis

“…In population-based studies, arthrotec was more effective than diclofenac and misoprotsol co-prescription in preventing hospitalization for peptic ulcer disease or gastrointestinal hemorrhage [18]. Several poly-pills containing NSAIDs and proton-pump inhibitors are approved for use in rheumatic diseases including ketoprofen with omeprazole (axorid) [19]. The combination of enteric-coated naproxen and the proton pump inhibitor esomeprazole (vimovo) was shown to reduce endoscopically detected gastric ulcers [20].…”

Current Perspectives in NSAID-Induced Gastropathy

“…Considerable reduction of adverse GI symptoms has been observed in patients prescribed with esomeprazole along with NSAIDs or selective COX-2 inhibitors [69, 70]. The first NSAID/PPI single tablet formulation to be approved is ketoprofen/omeprazole modified release capsules [71]. …”

Determination of Ibuprofen in Tablets and Human Blood Samples: Effect of Clay in Minimizing Overvoltage of Ibuprofen Oxidation

“…More than 900 drugs have been integrated as nonsteroidal anti‐inflammatory drug, among them, Ibuprofen (IUPAC name: (RS)‐2‐(4‐(2‐methylpropyl) phenyl) propanoic acid) . IBU is already in widespread use for pain and fever treatment and perceived to be an effective and safe drug when taken in the recommended dose.…”