NSAIDs Omeprazole

Clinically important, potentially hazardous interactions with acitretin, aldesleukin, aminoglycosides, amiodarone, amoxicillin, ampicillin, aspirin, bacampicillin, bismuth, carbenicillin, chloroquine, cisplatin, cloxacillin, co-trimoxazole, dapsone, demeclocycline, dexamethasone, diclofenac, dicloxacillin, etodolac, etoricoxib, etretinate, fenoprofen, flurbiprofen, folic acid antagonists, haloperidol, hydrocortisone, ibuprofen, indomethacin, influenza vaccines, ketoprofen, ketorolac, lithium, magnesium trisalicylate, meclofenamate, mefenamic acid, methicillin, mezlocillin, minocycline, nabumetone, nafcillin, naproxen, NSAIDs, omeprazole, oxacillin, oxaprozin, oxytetracycline, paromomycin, penicillin G, penicillin V, penicillins, phenylbutazone, piperacillin, piroxicam, polypeptide antibiotics, prednisolone, prednisone, probenecid, procarbazine, rofecoxib, salicylates, salsalate, sapropterin, sulfadiazine, sulfamethoxazole, sulfapyridine, sulfasalazine, sulfisoxazole, sulindac, tazobactum, tenoxicam, tetracycline, ticarcillin, tolmetin, trimethoprim, vaccines... 

C8 C9 C18 C19 C58P C62P Taxol (C8), NSAIDS, warfarin (C9), omeprazole (C19)... 

Refer to Chapter 14 on gastroesophageal reflux disease for more information on the PPIs. The PPI omeprazole is superior to both ranitidine and misoprostol for preventing recurrence of NSAID-associated PUD. In one study, omeprazole 20 mg daily was compared to misoprostol 200 meg twice daily for NSAID-associated PUD prevention. At 6 months, the omeprazole-treated group had significantly fewer ulcers than those taking misoprostol. Furthermore, more patients discontinued ulcer prophylaxis in the misoprostol group due to adverse events.26... 

Another study randomized patients requiring NSAID prophylaxis to either omeprazole 20 mg daily or ranitidine 150 mg twice daily.19 At 6 months, more patients who received omeprazole (72%) than ranitidine (59%) were in ulcer-free remission (p = 0.004). Omeprazole was also more efficacious in preventing GU recurrence than ranitidine (5.2% versus 16.3% p less than 0.01). Adverse drug events were similar in the two groups. 

Selective COX-2 inhibitors are not superior to PPIs in preventing NSAID-related PUD. One randomized, place-bo-controlled trial that included 267 patients at high risk for ulceration (arthritic patients with a previously healed bleeding ulcer) compared celecoxib 200 mg twice daily to the combination of diclofenac 75 mg twice daily plus omeprazole 20 mg daily.32 After 6 months, the risk for recurrent bleeding was found to be similar between groups (celecoxib, 4.9% and diclofenac/omeprazole, 6.4%) the authors concluded that neither of these therapies can completely prevent recurrent ulcer complications. 

Gastrointestinal ulceration may occur less frequently than with some other NSAIDs. A preparation combining diclofenac and misoprostol decreases upper gastrointestinal ulceration but may result in diarrhea. Another combination of diclofenac and omeprazole was also effective with respect to the prevention of recurrent bleeding, but renal adverse effects were common in high-risk patients. Diclofenac, 150 mg/d, appears to impair renal blood flow and glomerular filtration rate. Elevation of serum aminotransferases occurs more commonly with this drug than with other NSAIDs. 

The current therapy leaders are the anti-ulcerants such as Omeprazole (Prilosec ) or Lansoprazole (Prevacid ), which accounted for US 19.5 billion in 2001, thus claiming a market share of 6%. The anti-ulcerants are closely followed by the cholesterol reducers, e.g., Atorvastatin (lipitor ) and Simvastatin (Zocor ), totaling US 18.9 billion, the antidepressants (US 15.9 billion), and the NSAIDs (nonsteroidal anti-inflammatory drugs US 10.9 billion). Calcium antagonists, antipsychotics, oral antidiabetics, ACE inhibitors, cephalosporins, and antihistamines complete the list of the best-selling therapy classes, with sales between US 9.9 and 6.7 billion. It is interesting to note that four classes grew more than 20% in 2001, namely the cholesterol reducers (22%), the antipsychotics (30%), the oral antidiabetics (30%), and the antihistamines (22%) [4],... 

In a randomized comparison of celecoxib and diclofenac plus omeprazole, renal adverse events, including hypertension, peripheral edema, and renal insufficiency, were common and similar in the two groups (105). They occurred in the 24% of the patients who took celecoxib and in 31% of those who took diclofenac plus omeprazole. Among patients with renal impairment at baseline, 51% of those who took celecoxib and 41% of those who took diclofenac plus omeprazole had renal adverse events. Careful monitoring of renal function in patients taking COX-2 inhibitors or traditional NSAIDs is mandatory, especially in high-risk subjects (for example those with pre-existing renal disease, diabetes, or heart failure). 

Hawkey CJ, Karrasch JA, Szczepanski L, Walker DG, Barkun A, SwanneU AJ, Yeomans ND. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group. N Engl J Med 1998 338(ll) 727-34. 

This study has therefore shown that in patients infected with H. pylori who take low-dose aspirin, eradication of H. pylori is as effective as prophylactic therapy with omeprazole in preventing recurrent upper gastrointestinal bleeding. Therefore, patients taking aspirin for cardiovascular prophylaxis could be tested for H. pylori infection and treated for it if infection is confirmed. In contrast, omeprazole is superior to eradication of H. pylori for the secondary prevention of upper gastrointestinal bleeding in H. py/on-infected users of naproxen and presumably other non-aspirin NSAIDs. 

Graham DY. Critical effect of Helicobacter pylori infection on the effectiveness of omeprazole for prevention of gastric or duodenal ulcers among chronic NSAID users. Helicobacter 2002 7(l) l-8. 

NSAiDs, giafenin, ASA, fenoprofen, naproxen, phenyibutazone, piroxacam, tolemetin, zomepirac, contrast media, suifonamides, thiazides, phenytoin, furosemide, aiiopurinoi, cimetidine, omeprazole, phenindione. ... 

Allergic interstitial nephritis Penicillins, rifampin, sulfonamides, thiazides, cimetidine.phenytoin, allopurinol, furosemide, NSAIDS, ciprofloxacin, pantoprazole, omeprazole, atazanavir, bevacizumab Rash, fever, eosinophilia, eosinophiluria, pyuria... 

Standard PPI dosages (e.g., omeprazole 20 mg/day and lansoprazole 30 mg/day) reduce the risk of NSAID-induced gastric ulcer and duodenal ulcer. " In a large comparative multicenter trial, omeprazole 20 mg/day was superior to ranitidine 150 mg twice daily in preventing NSAID-induced gastroduodenal ulcers. Two randomized controlled trials have compared PPIs with misoprostol and placebo. 

Other agents have been evaluated in attempts to prevent NSAID-induced gastropathy. Among 935 NSAID users with baseline gastric or duodenal erosions, omeprazole and misoprostol were similarly effective in the treatment of ulcers and their symptoms, but omeprazole maintenance therapy conferred a lower rate of relapse. Thus several medications are available for the treatment or prevention of ulcers in high-risk patients. 

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