Bleeding diclofenac

Celecoxib, which has a low selectivity for COX-2 compared to COX-1, is still available, although its more selective successor, valdecoxib has been withdrawn. Etoricoxib, the successor to rofecoxib, is marketed in Europe but not in the USA. In a large multinational clinical trial, etoricoxib caused no more thromboembolic events than diclofenac, but after 18 months the incidence of gastrointestinal ulcers and bleeding was the same for both drugs [4]. 

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. 

Diclofenac is available as dispersible tablets, tablets, gel, suppositories and for intravenous or intramuscular injection. The maximum dose of diclofenac administered via any route is 150 mg. As v/ith other non-steroidal anti-inflammatory drugs, concomitant use in patients receiving venlafaxine increases the risk of bleeding. 

Avoid alcohol and aspirin during diclofenac therapy because these substances increase the risk of G1 bleeding... 

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. 

In the patient with contact lenses, it is advised not to use diclofenac preparations for ophthalamic treatment. Diclofenac also is contraindicated for intravenous administration in patients with renal impairment, hypovolemia, dehydration, asthma, or cerebrovascular bleeding. 

Diclofenac 50 mg prn Need to change to different pain control as high risk of bleeding when on warfarin and aspirin. Must not be taken as required. 

Diclofenac may be a second-line option, but it has a higher risk of both hepatotoxicity and GI bleeding than ibuprofen. 

HEPARINS ANALESICS - NSAIDs 1. Risk of prolonged bleeding when ketorolac is co-administered with dalteparin (but not enoxaparin), and intravenous diclofenac is given with heparins 2. t risk of hyperkalaemia when ketorolac is given with heparin 1. Uncertain 2. Heparin inhibits aldosterone secretion, causing hyperkalaemia 1. Avoid co-administration 2. Monitor potassium levels closely... 

Clinical trial evidence in general appears to support the theory that COX-2 selective inhibitors are as effective as, but have fewer adverse effects than, non-COX-2 selective compounds for example meloxicam is better tolerated than diclofenac or piroxicam. The relative risk of serious gastrointestinal effects (bleeding peptic ulcers) due to rofecoxib (COX-2 selective) was 0.51 compared with conventional NSAIDs. COX-2 selective drugs are yet associated with significant dyspeptic symptoms (indigestion, heartburn), and these effects may result from inhibition of the (protective) constitutively expressed COX-2 in the stomach. 

The same warning applies to evaluation of the incidence of complicated ulcers (bleeds, perforation, and obstructions). The incidence of these serious events with celecoxib was 2.7% (11 events) versus 5% (20 events) in patients taking diclofenac or ibuprofen, a non-significant difference. 

Diclofenac can cause panmyelopathy (8). Data from the International Agranulocytosis and Aplastic Anemia Study showed an increased risk of aplastic anemia (multivariate rate-ratio 8.8) (9). Fatal aplastic anemia has also been described (SEDA-4, 69) (10), as have purpura and thrombocytopenia, although not always with certainty. Spontaneous bleeding (subcutaneous bruises, hematoma, greater wound drainage) has been associated with diclofenac (SEDA-15,100). 

Gastrointestinal adverse effects are particularly frequent, and affect some 14-25% of patients the incidence of the most serious, peptic ulcer and bleeding were 0.16-0.34% and 0.16-0.17%, respectively (1). A prospective 12-week endoscopic study documented better gastrointestinal tolerability with diclofenac than naproxen (SEDA-20, 92). Upper gastrointestinal hemorrhage has been associated with transdermal application of diclofenac, with massive bleeding in two of four patients (SEDA-21, 104). 

To study effects on clinically important GI complications with celecoxib, the CLASS study used celecoxib (400 mg twice daily, or twice the highest FDA-approved dose) compared to diclofenac and ibuprofen at standard dose. Celecoxib use was reported to be associated with a reduced incidence for the combined end point of symptomatic ulcers and ulcer complications (perforations, gastric outlet obstruction, or bleeding). Some subjects also used aspirin for car-dioprotection, but there is concern that GI safety of COX-2 inhibitors is blunted with use of concomitant aspirin (even 30 mg of aspirin can suppress gastric prostaglandin prodnction)." For patients taking aspirin and celecoxib, nicer complications were higher than with celecoxib only, but lower than with traditional NSAIDs. 

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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