Peptic Ulcer Disease Associated with NSAIDs
Peptic Ulcer Disease Associated with NSAIDs
By Joan A. Unger, RN, MS, ARNP-C
Summary-Nonsteroidal anti-inflammatory drugs (NSAIDs) are the second most common cause of peptic ulcer disease. (Helicobacter pylori infection is first.) Preferred treatment is to discontinue NSAIDs, but this is often impossible in chronic, painful conditions such as arthritis. Studies found omeprazole and misoprostol similar in successfully treating ulcers, erosions, and symptoms associated with NSAID use. Omeprazole was more effective than ranitidine. Patients on maintenance therapy had a lower rate of recurrence with omeprazole than with misoprostol or ranitidine, and omeprazole was better tolerated. Single daily dosing with omeprazole as opposed to multiple daily doses with ranitidine or misoprostol may be helpful when patient compliance is a concern.
Each year, 500,000 new cases and 4 million recurrences of peptic ulcer disease (PUD) are diagnosed in the United States. Fifteen years ago, most peptic ulcers were considered idiopathic or a result of stress, alcohol, or dietary factors. Today alcohol and diet aren't considered causative, and we're uncertain about stress. We do know that smokers and regular users of NSAIDs are at high risk.
In fact, the second most common cause of PUD is the use of NSAIDs. (H. pylori infection is first.)1 Ten to 20% of chronic NSAID users develop gastric ulcers, and 2-5% develop duodenal ulcers. NSAID users are three times as likely as nonusers to suffer complications such as gastrointestinal bleeding, perforation, or death. The risk of complications increases with higher NSAID dosage, advanced age, concomitant use of corticosteroids, serious medical illness, or prior history of ulcers.1
The New England Journal of Medicine reported on two studies comparing the efficacy and tolerability of oral medications commonly used to treat peptic ulcers. The studies were international, double-blind, randomized comparisons in subjects ages 18-85 who required continuous NSAID therapy and no more than 10 mg of prednisolone or its equivalent daily.
The studies had two phases: healing and maintenance. All subject candidates underwent endoscopy. Those who had any of the following were invited to participate: ulcers 3 mm or more in diameter, or more than 10 gastric or 10 duodenal erosions.
Major exclusion criteria were concurrent esophagitis, active gastrointestinal bleeding, pyloric stenosis, or conditions that might impair absorption of the study drugs. Subjects were tested for H. pylori but were not treated because prior studies produced no evidence that treatment was beneficial.2,3 Prior studies also suggested that H. pylori-stimulated mucosal synthesis of prostaglandin may benefit NSAID-associated ulcers.4 Treatment success, defined in advance, was absence of ulcers in the stomach or duodenum, fewer than five stomach or duodenal erosions, and no more than mild dyspepsia.
Study No. 1 also excluded subjects with a history of gastric surgery.5 This study compared omeprazole (Prilosec, Astra Merck, Wayne, PA) 20 mg or 40 mg daily with misoprostol (Cytotec, GD Searle and Co., Skokie, IL) 200 mcg four times daily in 935 patients randomly assigned to treatment groups. Endoscopy was repeated after four weeks of treatment and again at eight weeks if lesions were not healed. If lesions were not healed after eight weeks, subjects received omeprazole for an extra 4-8 weeks.
At eight weeks, the study found successful healing in 76% of patients taking 20 mg of omeprazole, 75% of patients taking 40 mg of omeprazole, and 71% of those receiving misoprostol. Duodenal ulcer healing was higher with either dose of omeprazole than with misoprostol. Gastric ulcer healing was higher with 20 mg of omeprazole (but not with 40 mg) than with misoprostol. Healing of erosions was higher with misoprostol. Patients who were successfully healed (732) received maintenance therapy of 20 mg omeprazole daily, 200 mcg of misoprostol twice daily, or a placebo for six months. On maintenance therapy, more patients remained symptom-free with omeprazole (61%) than with misoprostol (48%). Only 27% of placebo patients were in remission. More adverse events (primarily abdominal pain) were reported with misoprostol, and omeprazole was better tolerated than misoprostol.
Quality of Life Addressed
Investigators also evaluated dyspeptic symptoms and quality of life. Results were similar, with omeprazole providing more relief than misoprostol except in sleep score, which improved more on misoprostol than omeprazole. Researchers conclude:
· Successful results of treatment with omeprazole and misoprostol were similar.
· Maintenance therapy was more successful with omeprazole.
· Omeprazole was better tolerated than misoprostol.5
In study No. 2, neck instability that might compromise endoscopy also was excluded.6 This study compared omeprazole 20 mg or 40 mg daily with ranitidine (Zantac, Glaxo Wellcome, Research Triangle Park, NC) 150 mg twice daily in 541 patients randomly assigned to treatment groups. At eight weeks, 80% of patients taking 20 mg of omeprazole, 79% of patients taking 40 mg of omeprazole, and 63% percent of those receiving ranitidine showed successful healing. Rates of healing were higher with omeprazole than with ranitidine for all types of ulcers.
After 4-8 weeks, depending on the rate of healing, 425 of the successfully treated patients were placed on maintenance therapy of 20 mg omeprazole daily or 150 mg ranitidine twice daily for six months. After six months, the estimated proportion of patients in remission was 72% of the omeprazole group and 59% of the ranitidine group. Rates of adverse events were similar, and both medications were well-tolerated. The study found higher rates of success in H. pylori-positive patients than in those who were H. pylori-negative in both the healing and maintenance phases. Researchers conclude that omeprazole is more effective than ranitidine in healing and preventing ulcers.4
Practice Implications
Given the optimistic outlook of treatment with omeprazole,, advanced practice nurses may want to consider its use in their practices. Omeprazole is an acid pump inhibitor indicated for short-term treatment of active benign gastric ulcers, active duodenal ulcers, symptomatic gastroesophageal reflux disease (GERD), and in combination with clarithromycin (Biaxin, Abbott Laboratories, Abbott Park, IL) for treating active duodenal ulcers associated with H. pylori infection. It is supplied in 10 mg or 20 mg capsules containing enteric-coated delayed-release granules. The following are recommended protocols for omeprazole.
· Active duodenal ulcer: 20 mg daily for four weeks and continue for four more weeks if indicated.
· Gastric ulcer: 40 mg once daily for 4-8 weeks.
· GERD with no esophageal lesions: 20 mg daily for up to four weeks.
· Erosive esophagitis with GERD symptoms: 20 mg daily for 4-8 weeks.
· If relapse of erosive esophagitis or GERD symptoms recur, give four to eight more weeks.
· To reduce the risk of duodenal ulcer recurrence: omeprazole 40 mg once daily in a.m. plus clarithromycin 500 mg tid on days one to 14, then ome prazole 20 mg once daily in a.m. on days 15-28.
· Advise patients to take omeprazole before eating and not crush, chew, or open capsules. Use caution when prescribing for patients with renal dysfunction (CrCl<30 mg/min); reduce clarithromycin dose. Omeprazole is not recommended for pregnant and nursing mothers.
· The drug may potentiate diazepam, phenytoin, and warfarin. It may alter absorption of ketoconazole, digoxin, iron, and ampicillin. Give at least 30 minutes before sucralfate, but you may give concomitantly with antacids. Possible adverse reactions include headache, diarrhea, dizziness, rash, constipation, cough, and back or abdominal pain.7
References
1. McQuaid KR. Alimentary tract. In Current Medical Diagnosis and Treatment. Stamford, CT: Appleton and Lange; 1997, pp. 559-567.
2. Cullen D, Hawkey G, Humphries H, et al. Role of non-steroidal anti-inflammatory drugs and Helicobacter pylori in bleeding peptic ulcer. Gastroenterology 1994;106:Supp:A66.
3. Cullen D, Hawkey G, Greenwood D, et al. Peptic ulcer bleeding in the elderly: Relative roles of Helicobacter pylori and non-steroidal anti-inflammatory drugs. Gut 1997;41:459-62.
4. Hudson N, Balsitis M, Filipowicz F, et al. Effect of Helicobacter pylori colonisation on gastric mucosal eicosanoid synthesis in patients taking non-steroidal anti-inflammatory drugs. Gut 1993;34:297-300.
5. Hawkey C, Karrasch J, Szczepanski L, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal anti-inflammatory drugs. N Engl J Med 1998;338:727-734.
6. Yeomans N, Tulassay Z, Juhasz L, et al. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal anti-inflammatory drugs. N Engl J Med 1998;338:719-726.
7. Murphy J, ed. Nurse Practitioners' Prescribing Reference. New York City: Prescribing Reference; 1998;5: 122,125.
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