Long-term tolerability of the combination naproxen and esomeprazole magnesium in fixed dose

Gastrointestinal risk factors have been extensively studied. During the last CNS Latin American Forum on pain, Dr. Angel Lanas explained that in the last 10 years there has been an important reduction of complications in the upper gastrointestinal tract, although complications in the lower gastrointestinal tract have increased.

In view of this situation, Lanas considered that it is essential to define an ideal strategy to achieve the protection of both digestive tracts. At the same time, special attention should be paid to those patients who may develop an ulcer.

In line with the above, it is pertinent to mention a study published in Current Medical Research and Opinion. The objective of this study was to assess the long-term tolerability of the combination of enteric-coated naproxen at a dose of 500 mg and immediate-release esomeprazole magnesium at a fixed dose of 20 mg (FDC) in patients at risk of NSAID-related gastric ulcers.

This was an open-label, multicenter, phase III study involving Helicobacter pylori-negative patients aged ≥50 50 years or 18 to 49 years with a history of uncomplicated ulcer in the past five years. Patients in turn had osteoarthritis, rheumatoid arthritis, or other disorder requiring daily NSAIDs for ≥12 months, received naproxen/esomeprazole twice daily for 12 months.

The primary endpoints consisted of adverse effects, vital signs, physical examination, and laboratory tests. Subgroup analyses included use of low-dose acetylsalicylic acid (LDA) and age.

Adverse effects of NSAID-related gastric ulcer and predefined cardiovascular adverse effects were analyzed.
Of 239 treated patients (tolerability population), 135 completed ≥ 348 days of treatment (those who completed 12 months). The frequency of adverse effects was approximately 70%; dyspepsia, constipation, upper respiratory infections, nausea, dorsalgia, and contusion were most frequent (≥ 5 patients, in each population).

Treatment-related adverse effects occurred in 28.0% and 23.7% of patients in the tolerability and 12-month completion populations, respectively; 18.8% of patients discontinued medication as a result of adverse effects (tolerability population).
There were few serious adverse effects and no deaths. In the tolerability population, the frequency of adverse effects was 71.4% and 76.9% in patients <65 years of age (n = 161) and ≥65 years (n = 78), respectively, and 67.6% and 75.8% in LDA users (n = 74) and nonusers (n = 165), respectively.

High digestive and cardiovascular adverse effects were observed in 18.8% and 6.3% of patients, respectively, in the tolerability population and 16.3% and 5.2%, respectively, in those concluding 12 months of treatment. Dyspepsia and hypertension were more frequent. Additional assessments showed no unexpected findings.

Based on these endpoints, long-term treatment with FDX naproxen/esomeprazole was not associated with any new tolerability issues, including predefined UGI and cardiovascular adverse effects, in patients requiring NSAID therapy who were at risk for upper gastrointestinal complications.

Source: Medcenter Medical News