Misoprostol Diclofenac

Pharmacokinetics The pharmacokinetics following oral administration of a single dose or multiple doses of diclofenac/misoprostol to healthy subjects under fasted conditions are similar to the pharmacokinetics of the 2 individual components. Food decreases the multiple-dose bioavailability profile of both formulations. 

Schai f S, Mander A, Ugoni A, Vajda F, Christopliidis N (1999) A double blind placebo cond olled dial of diclofenac/misoprostol in Alzheimer s disease. Neui ology 53 197-201. 

Goldstein JL, Larson LR, Yamashita BD. Prevention of nonsteroidal anti-inflammatory drug-induced gastropathy clinical and economic implications of a single- tablet formulation of diclofenac/misoprostol. Am J Manag Care 1998 May 4(5) 687-697. 

The misoprostol in diclofenac + misoprostol is extensively absorbed, and is metabolized rapidly to its active metabolite, misoprostol acid. Misoprostol acid reaches peak plasma concentration within 20 minutes and has an elimination half-life of 30 minutes. No accu-m ulation of misoprostol acid has been found. The serum protein binding of this metabolite is less than 90%. Approximately 70% of misoprostol is excreted in the urine. Activity of misoprostol is evident within 30 minutes of administration and lasts for 3 hours. Administration of diclofenac and misoprostol together as diclofenac + misoprostol leads to similar absorption and elimination as when the two are administered alone. 

Arthrotec 50/0.2, 75/0.2 diclofenac/misoprostol. Common doses include 1 tab PO TID-QID, with a maximum dose of 225 mg/day diclofenac. 

Arthrotec tablets contain the non-steroidal anti-inflammatory drug diclofenac and the prostaglandin misoprostol. The combination of the two active ingredients makes Arthrotec suitable in patients predisposed to gastrointestinal ulceration. Dulco-lax (bisacodyl) tablets act as a stimulant laxative. Voltarol Retard tablets contain the non-steroidal anti-inflammatory drug diclofenac. All... 

Tablets 50 mg diclofenac sodium/200 meg misoprostol and 75 Arthrotec mg diclofenac sodium/200 meg misoprostol Rx) (Searle)... 

Rheumatoid arthritis Recommended dose is 50 mg diclofenac/200 meg misoprostol 3 or 4 times/day. For patients who experience intolerance, 50 mg/200 meg or 75 mg/200 meg twice/day can be used, but are less effective in preventing ulcers. Do not exceed 225 mg of diclofenac per day. 

Hypersensitivity to diclofenac or to misoprostol or other prostaglandins. Do not give to patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. 

Geriatric Considerations - Summary Use of NSAIDs in older adults increases the risk of GI complications including gastric ulceration, bleeding, and perforation. These complications are not necessarily preceded by less severe GI symptoms. Concomitant use of a proton pump inhibitor or misoprostol reduces the risk for gastric ulceration and bleeding, but may not prevent long-term GI toxicity. No clinical data exist to support reduced GI toxicity with the use of diclofenac. 

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. 

Johnston SA, Leib MS, Forrester SD, Marini M (1995) The effect of misoprostol on aspirin-induced gastrointestinal lesions in dogs. J Vet Intern Med 9 32-38 Matsui H, Murata Y, Kobayashi F et al. (2001) Diclofenac-induced gastric mucosal fluorescence in rats. Dig Dis Sci 46 338-344... 

In practice, a minority of patients are intolerant of aU NSAIDs. They may benefit from the co-administration of a proton pump inhibitor, a 112-receptor blocker or the prostaglandin analogue, misoprostol. To address this problem, some NSAIDs are presented in combination with misoprostol, e.g. diclofenac with misoprostol (Arthrotec) and naproxen with misoprostol (Napratec). Some patients experience abdominal pain and diarrhoea from the misoprostol component. 

In contrast to the above results, Boers and colleagues [182] failed to detect any beneficial effects of misoprostol in a double-blind, crossover study of diclofenac-treated patients with renal insufficiency (creatinine clearance < 80 ml/min/1.73 m ). Renal prostaglandin production was not measured in this study, which precludes any conclusions regarding the interactions between misoprostol and NSAID on prostaglandins. It is conceivable that the dose of misoprostol (200 pg three times daily) used was inadequate to prevent NSAIDs from suppressing renal prostaglandin production. Alternatively, the dose (50 mg three times daily) and duration (14 to 21 days) of diclofenac may not have been sufficient to suppress urinary prostaglandins or renal function. Furthermore, as noted by the authors of this study, NSAID therapy was not withdrawn, so the effect of diclofenac on renal function is tmclear. 

PIncus T, Koch GG, Sokka T, et al. A randomized, double-blind crossover clinical trial of diclofenac versus misoprostol versus acetaminophen in patients with osteoarthritis ofthe knees or hip. Arthritis Rheum 2001 44 1587-98. 

Boers M, Dijkmans BA, Breedveld FC et al. No effect of misoprostol on renal function of rheumatoid patients treated with diclofenac. British Journal of Rheumatology 1991 30 56-59. 

NSAIDs (nonsteroidal antiinflammatory drugs) Isolated cases of adverse neurological side effects have been seen with naproxen or phenylbutazone given with misoprostol. Misoprostol also increases the abdominal pain and other side effects of diclofenac and indometacin (indomethacin). Paracetamol (acetaminophen) intensifies pain if given with mifepristone and sulprostone used to induce abortion. 

Arthrotec misoprostol diclofenac, articaine [ban, inn) (carticaine) is an amide series local ANAESTHETIC, injected for dental and infiltration pain relief. Artracin indomethacin. 

Aside from consideration of the relatively uncommon but serious GI adverse effects described above, fewer overall GI complaints from patients are found for COX-2 inhibitors compared to nonspecific NSAIDs. Moreover, celecoxib use was associated with decreased outpatient physician claims for upper GI symptoms compared with other prescription nonspecific NSAIDs. Finally, celecoxib was comparable to a combination of diclofenac and misoprostol in reducing the risk of recurrent GI bleeding in patients who had a prior GI bleed. ... 

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