Omeprazole Diclofenac

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. 

Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl f Med 2002 347 2104-2410. 

GFJ has been shown to increase the exposure of carbamazepine (175), cisapride (176-179), fluvoxamine (184), losartan (188), methadone (189), scopolamine (191), and sertraline (192). However, only the interaction of GFJ with carbamazepine and cisapride seems to be clinically relevant. No alteration in exposure was observed for clozapine (180,181), heophylline (195), halo-peridol (196), and omeprazole (190). Reports of increased pharmacokinetic parameters of clozapine, theophylline, and haloperidol suggest that an interaction is unlikely to be clinically relevant. Contradicting results were reported for itraconazole (185-187), digoxin (75,183), and sildenafil (193,194). An increased effect on concomitant use of diclofenac and GFJ was observed in rats (182). Overall, the clinical relevance for this drug class appears to be low. 

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. 

In view of their incomplete oral bioavailability, several CYP2C substrates may undergo significant first-pass intestinal metabolism, including the CYP2C9 substrates verapamil (155), losartan (156), fluvastatin (157), and diclofenac (158), and the CYP2C19 substrates (5)-mephenytoin (159) and omeprazole... 

TLC has been used for the impurity analysis of ciprofloxacin, diclofenac, chlor-promazine, trifluoropromazine, doxepine, alprazolam, omeprazole, pantoprazole, tetracycline, and chlortetracycline [35 1] other examples can be found in the work of Ferenczi-Fodor et al. [42],... 

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). 

To test whether omeprazole accelerates healing of standardized gastroduodenal lesions in the presence of diclofenac, 12 healthy volunteers took consecutive 2-week courses of omeprazole 40 mg/day or placebo, with diclofenac given in the second week of each course, in a double-blind, crossover study (3). Omeprazole did not accelerate the healing of pre-existing mucosal lesions or prevent the development of small diclofenac-induced mucosal lesions. Omeprazole increased serum gastrin in all subjects. 

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... 

---