Celecoxib Aspirin

Jenkins C, Costello J, Hodge L Systematic review of prevalence of aspirin-induced asthma and its implications for clinical practice. BMJ 2004 328 434-437. Baldassarre S, Schandene L, Choufani G, Michils A Asthma attacks induced by low doses of celecoxib, aspirin and acetaminophen. J Allergy Clin Immunol 2006 117 215-217. 

A Acetaminophen would be the drug of choice to try in this patient. If an adequate response were not achieved, due to the patient s age and medical history, it would be reasonable to begin a COX-2 inhibitor such as celecoxib. Aspirin, ibuprofen, and indomethacin should be avoided in this patient with a history of Gl bleeding. 

Acute generalized exanthematous pustulosis (AGEP) Ibuprofen, nimesulide, etoricoxib, valdecoxib, celecoxib, aspirin, acetaminophen Reactions rare... 

Celecoxib is contraindicated in patients who are allergic to die drug itself, die sulfonamides, odier NSAIDs, or aspirin it also is contraindicated during pregnancy (Category C) and lactation. 

COX-2 inhibitors such as celecoxib are associated with adverse effects such as nephrotoxicity and a potential increased risk of myocardial infarction (see Chaps. 55 and 15 for additional information). Combination of COX-2 inhibitors with alcohol may increase GI adverse effects. All NSAIDs should be used with caution in patients with aspirin-induced asthma.31... 

While aspirin is equipotent at inhibiting COX-2 and COX-1 enzymes in vitro and ibuprofen demonstrates a sevenfold greater inhibition of COX-1, other NSAIDs appear to have partial COX-2 specificity, particularly meloxicam. A search for COX-2-speciflc inhibitors resulted in promising candidates such as valdecoxib, celecoxib and rofecoxib. A 30-300 higher potency for inhibiting COX-2, than COX-1, suggested the possibility of relief from pain... 

Aspirin is one of the most important NSAIDs because it decreases pain at predominantly peripheral sites with little cortical interaction and thus has few CNS effects. The prototypical COX-2 inhibitors are celecoxib (Celebrex) and its chemical cousin, rofecoxib (Vioxx). In addition to a role in inflammatory processes,... 

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

Indomethacin and sulindac are slightly selective for COX-1. Meclofenamate and ibuprofen are approximately equipotent on COX-1 and COX-2, whereas celecoxib = diclofenac < rofecoxib = lumiracoxib < etoricoxib in inhibition of COX-2 (listed in order of increasing average selectivity). Aspirin acetylates and inhibits both enzymes covalently. Low doses (< 100 mg/day) inhibit preferentially, but not exclusively, platelet COX-1, whereas higher doses inhibit both systemic COX-1 and COX-2. 

Selectivity for COX-1 versus COX-2 is variable and incomplete for the older NSAIDs, but many selective COX-2 inhibitors have been synthesized. The selective COX-2 inhibitors do not affect platelet function at their usual doses. In testing using human whole blood, aspirin, ibuprofen, indomethacin, piroxicam, and sulindac are somewhat more effective in inhibiting COX-1. The efficacy of -2-selective drugs equals that of the older NSAIDs, while gastrointestinal safety may be improved. On the other hand, selective COX-2 inhibitors may increase the incidence of edema and hypertension. As of December 2008, celecoxib and the less selective meloxicam are the only COX-2 inhibitors marketed in the USA. Rofecoxib and valdecoxib, two previously marketed, selective COX-2 inhibitors, have been withdrawn from the market due to their association with increased cardiovascular thrombotic events. Celecoxib has an FDA-initiated "black box" warning concerning cardiovascular risks. It has been recommended that all NSAID product labels be revised to include cardiovascular risks. 

Cortisol inhibits phospholipase A2 and COX-2. Non-steroidal antiinflammatory drugs, such as aspirin, inhibit both COX-1 and COX-2, whereas celecoxib inhibits COX-2. 5-Lipoxygenase inhibitors are used in the treatment of asthma. 

Ongoing research led to the development of COX-2 selective inhibitors (e.g., rofecoxib and celecoxib). Celecoxib (Celebrex ) was approved by the FDA in 1998 to treat osteoarthritis and rheumatoid arthritis. Rofecoxib (Vioxx ) was approved in May 1999 to treat osteoarthritis, acute pain, and dysmenorrhea. Sales for the two drugs in 1999 were 1.5 billion and 373 million, respectively. Clinical studies have indicated a significant reduction in GI perforation, ulceration, or bleeding with the COX-2 inhibitors. The recognition of multiple COX isoforms has had one of the greatest impacts on the development of NSAIDs since the original synthesis of aspirin more than a century ago. 

NONE All over-the-counter pain relievers (i.e., aspirin, acetaminophen, ibuprofen, naproxen, etc.), prescription antidepressants, anticonvulsants, muscle relaxants (except benzodiazepines), migraine medications, steroids, celecoxib, BoTox, herbal remedies, tramadol, local caine family (except cocaine)... 

Celecoxib [sel eh COCKS ib] is significantly more selective for inhibition of COX-2 than of COX-1 (Figure 39.16). In fact, at concentrations achieved in vivo, celecoxib does not block COX-1. Unlike the inhibition of COX-1 by aspirin (which is rapid and irreversible), the inhibition of COX-2 is time-dependent and ireversible. Celecoxib was approved for treatment of osteoarthritis and rheumatoid arthritis, but not for analgesia. [Note In some trials, celecoxib had analgesic activity in others it was no more effective than the placebo. Its ability to reduce acute pain is poor.] Unlike aspirin, celecoxib does not inhibit platelet aggregation, and does not increase bleeding time. 

In VIGOR, rofecoxib 50 mg/day was associated with a higher rate of non-fatal myocardial infarction (0.4%) than the non-selective COX-2 inhibitor naproxen 500 mg bd (0.1%) (RR = 0.2 Cl = 0.1, 0.7) (33). In CLASS there was no difference in the rates of myocardial infarction in patients taking celecoxib (0.5%) and those taking ibuprofen or diclofenac (0.4%). However, the protocols of the two studies differed substantially with respect to the use of aspirin. In VIGOR, the patients were not allowed to take aspirin or any other antiplatelet drug, while in... 

CLASS one-fifth of the patients took aspirin. A re-analysis of CLASS for cardiovascular thromboembolic events, including myocardial infarction, stroke, cardiovascular deaths, and peripheral events, showed no significant increase with celecoxib versus NSAIDs (35). 

Moreover, the overall incidence of gastrointestinal symptoms in patients taking celecoxib was only slightly lower than that of patients taking the traditional NSAIDs, as was the rate of withdrawal due to gastrointestinal intolerance in both users and non-users of low-dose aspirin. 

However, these results must be treated with great caution, as the total number of patients who took prophylactic aspirin was small (150 taking celecoxib and 140 taking non-selective NSAIDs) and the largest number of patients came from a single trial (CLASS). 

Dahlen B, Szczeklik A, Murray JJ Celecoxib in Aspirin-Intolerant Asthma Study Group. Celecoxib in patients with asthma and aspirin intolerance. N Engl J Med 2001 344(2) 142. 

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