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HYPERSENSITIVITY TO NONSTEROIDAL ANTI-INFLAMMATORY DRUGS:
FROM PATHOGENESIS TO CLINICAL PRACTICE / ARTIGO DE REVISÃO

nimesulide up to 5mg/kg/day (cumulative daily dose up to Studies suggested that coxibs can be safely used in
200mg). This drug is approved in pediatric patients 12 patients with previous hypersensitivity reactions to
years of age and older, and for no longer than a 15 -day COX -1 inhibitors NSAIDs . However allergic reactions,
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course treatment. including severe reactions, have also been described 42, 43 .
These new drugs are considered to be promising, with
2.2. Meloxicam equivalent anti -inflammatory efficacy and lower rate of
Meloxicam is a preferential COX -2 inhibitor at lower gastrointestinal effects.
doses (7.5 mg). However, when taken at higher doses it Celecoxib was the first COX -2 inhibitor approved by
can also inhibit COX -1 (dose -dependent mechanism). the FDA (1998), followed by rofecoxib (1999). However,
Meloxicam 7.5 -15 mg/day is as efficient as conventional rofecoxib was withdrawn from the market after a clinical
NSAIDs (like diclofenac), in osteoarthrosis, rheumatoid trial, since it has been associated with an increased risk
arthritis and other rheumatologic diseases which require of myocardial infarction. Subsequently, parecoxib, valde-
chronic anti -inflammatory and analgesic therapy, but coxib, etoricoxib and lumiracoxib were developed. The
studies have reported its superior gastrointestinal toler- lack of adequate data on the cardiovascular safety, along
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ability comparing to conventional NSAIDs . with the increased risk of adverse cardiovascular events
Many studies assessed tolerance to meloxicam, either and reports of serious and potentially life -threatening
with low dose of 7.5mg or 15mg 36 -38 . According to pub- skin reactions lead to voluntarily withdraw of valdecoxib
lished studies, 91 to 99% of patients with NSAIDs hyper- from the market in 2005. In 2007, lumiracoxib was sus-
sensitivity are tolerant to meloxicam. In a Portuguese pended due to severe hepatotoxicity. Currently, only
study, in patients with NSAIDs hypersensitivity, where celecoxib, parecoxib and etoricoxib are available. Cele-
68 oral challenges with meloxicam have been performed, coxib is approved in adults and etoricoxib for adults and
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19% of patients reacted . Gathering all these results, at adolescents over 16 years old.
lower doses meloxicam has proven to be associated to In most patients COX -2 inhibitors are considered to
a low rate of allergic reactions (about 5%), being the ma- be suitable and safe alternative drugs. Weberstock et al.
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jority only cutaneous . Meloxicam is a better alternative, reviewed 84 studies about the severity and the type of
comparing to nimesulide. However, patients should be adverse reaction to coxibs, and 13 of them described
advised to avoid doses higher than 15mg daily in order to double -blind COX -2 inhibitor challenges to determine
prevent a potential COX -1 inhibition. the probability of adverse reactions to coxibs; 119 pa-
Few studies were accomplished in pediatric age; thus tients (3.6%) reacted with COX -2 inhibitors from a total
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the prescription of meloxicam is not recommended under of 3304 patients. Asero et al. described a higher rate of
16 years old. coxibs hypersensitivity up to 33%. A high percentage of
A parenteral formulation of meloxicam is available, positive challenges (21%) was also found by Malskat et
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which offers an advantage, in case of surgery for instance. al. , whose study demonstrated that a second challenge
Based on the patient’s needs, meloxicam might be con- with a different COX -2 inhibitor can provide a safe alter-
sidered the first alternative in these patients. native. A study performed in 47 patients with cross-
-intolerance to NSAIDs and intolerance to paracetamol
3. Selective COX -2 inhibitors showed that 25% were intolerant to etoricoxib, whereas
Selective COX -2 inhibitors (coxibs) are assumed to among those with cross -intolerance to NSAIDs and good
be a safe alternative in patients susceptible to non- tolerance to paracetamol (n=50) only 6% showed to be
-selective NSAIDs. intolerant to etoricoxib .
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