Safety of selective cyclooxygenase‐2 inhibitors and a basic non‐steroidal anti‐inflammatory drug (NSAID) in Japanese patients with NSAID‐induced urticaria and/or angioedema: Comparison of meloxicam, etodolac and tiaramide

Abstract

The identification of a safe and reliable alternative for patients with non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema is a frequent problem for dermatologists and other practitioners. Cyclooxygenase-2 (COX-2) inhibitors have been reported to be safe for NSAID-intolerant patients from the US and Europe but not all of them have yet been approved for use in Japan. It was our objective to investigate the clinical manifestations of oral NSAID challenges in Japanese patients with histories of urticaria and/or angioedema after the intake of NSAIDs and to find safe alternative drugs, including COX-2 inhibitors and a basic anti-inflammatory drug. Twenty subjects suspected NSAID-induced urticaria/angioedema from histories were included in a double-blind or single-blind, placebo-controlled oral challenge protocol using NSAIDs. Skin prick tests using NSAIDs, which were dissolved in saline, were conducted. The mean age of the patients was 37.3 years; 14 patients were female. The results of other challenge tests showed that the most frequently intolerated drugs was loxoprofen (100%), followed by acetyl salicylic (94.4%), etodolac (53.3%), dicrofenac (50%), acetaminophen (38.5%), meloxicam (33%), and tiaramide (21.4%). Urticaria and angioedema were induced after aspirin intake in 83.3% and 22.2% of patients, respectively, whereas an asthmatic response was seen in 5.6%. Skin prick tests with NSAIDs were 100% negative. This study showed that among the NSAIDs that are available in Japan and that were investigated in this study, tiaramide, which does not inhibit COX, is the relatively safe alternative drug for Japanese patients with NSAID-induced urtiacaria and/or angioedema. Furthermore, meloxicam seems to be better tolerated than etodolac between two selective COX-2 inhibitors.

Safety of meloxicam in patients with aspirin/non‐steroidal anti‐inflammatory drug‐induced urticaria and angioedema

“…In the present study, we found that the majority of patients (91.4%) with ASA‐induced UR/AE perfectly tolerated a 7.5‐mg therapeutic dose of meloxicam The safety of meloxicam has been demonstrated in our previous studies in ASA/NSAID‐intolerant patients with different clinical pattern of intolerance reaction 4,12 but not specifically in patients with ASA‐induced UR/AO. In the current study, as consistent with other previous data, meloxicam appeared to be a very safe alternative for patients with ASA/NSAID‐induced UR/AE 18–22 …”

“…Meloxicam was challenged in only two patients and with a negative result among 15 patients with challenge‐proven NSAID‐induced UR/AE 24 . In another challenge‐proven study with 20 patients from Japan, six patients challenged with 10 mg of meloxicam and two responded (33.3%) with UR/AE 22 …”

“…Reactions to meloxicam were observed in only 10 patients (8.6%) in our group. The analysis of available data exhibits variable rates of intolerance to meloxicam, ranging 1.35–33.3% 18–22 . Discrepancies between different studies may be related to methodology, selection of the patients, dose of the drug and the number of patients involved.…”

“…Also, the average relative risk of urticaria (UR)/angioedema (AE) in a large cohort of patients exposed to these agents was between 1.1% (for those who used NSAIDs chronically) and 3.6% (for those who took NSAIDs intermittently, for treatment of acute pain) 17 . However, there are only a few studies evaluating the safety of meloxicam in patients with ASA/NSAID‐induced UR/AE 18–22 . Therefore, in this study we aimed to assess the tolerability of meloxicam specifically in patients with NSAID‐induced UR/AE.…”

“…17 However, there are only a few studies evaluating the safety of meloxicam in patients with ASA ⁄ NSAIDinduced UR ⁄ AE. [18][19][20][21][22] Therefore, in this study we aimed to assess the tolerability of meloxicam specifically in patients with NSAID-induced UR ⁄ AE.…”