Drugs that are usually tolerated well, such as paracetamol, may induce asthma attacks when higher than recommended doses are given to people who are intolerant to nonsteroidal antiinflammatory drugs (NSAIDs) ( 1 ). Rofecoxib is usually recommended at doses of 12.5 or 25 mg, but higher doses can be prescribed. Because the safety of high doses has not been explored, this study aimed to assess the tolerability of 50 mg of rofecoxib (Vioxx, MSD) in NSAID-intolerant people.
Ninety-three people were included in the study: 66 women and 27 men with a mean age of 43 ± 15 (SD) years (range 18–78). Fifty-eight patients had experienced nonallergic cutaneous reactions (urticaria and/or angioedema) and 43 asthma attacks after taking therapeutic doses of various NSAIDs (2).
After written consent had been given, a single-blind placebo-controlled challenge with rofecoxib was carried out on two study days, separated by 7–14 days. On day 1 the challenge consisted of placebo, rofecoxib 6.125 mg, rofecoxib 12.5 mg; and on day 2, placebo, rofecoxib 25 mg, rofecoxib 25 mg. The maximal cumulative dose was 50 mg.
Forced spirometry was monitored at baseline, during the administration of the doses, and within 3 h after the last dose had been given.
A questionnaire and a peak expiratory flow (PEF) meter were given to each patient to record any delayed adverse reactions within the 24 h after the tolerance test.
The oral tolerance test was positive when any of the following criteria were met: urticaria and/or angioedema; a decrease of 20% or more from the baseline value in forced expiratory volume in 1 s (FEV1); the occurrence of a delayed asthmatic reaction, defined as a decrease of 30% or more in the PEF from baseline.
The NSAIDs involved in adverse reactions are shown in Table 1.
|Niflumic acid||1 (1%)|
One person with previous history of NSAID-induced urticaria developed urticaria 24 h after rofecoxib challenge. The remaining 92 patients tolerated 50 mg of rofecoxib without any immediate or late-phase reaction.
Rofecoxib has proved to be very well tolerated by NSAID-sensitive asthma patients. In two separate studies Szczeklik et al. (3) and Stevenson et al. (4) challenged 12 and 60 acetylsalicylic acid (ASA)-intolerant asthmatics, respectively, with rofecoxib; none of them experienced any symptoms or decline in FEV1 values. Similarly, we report 43 NSAID-sensitive asthmatic people who tolerated rofecoxib. In contrast to previous studies, we challenged our patients with 50 mg of rofecoxib. This dose may be needed when potent analgesia or antiinflammatory effects are required. Our results add to the evidence that rofecoxib is a well-tolerated antiinflammatory drug that can be prescribed safely to patients who have NSAID-induced asthma.
Adverse cutaneous and systemic reactions precipitated by rofecoxib have been reported (5–7). However, we observed a delayed urticarial reaction in only one of the 58 people tested, and this was with a higher dose of rofecoxib than used in studies by Asero (5), Sanchez-Borges et al. (6) and Nettis et al. (7). The reasons are unclear for the high prevalence of adverse reactions in some studies.
In summary, rofecoxib—even at a high dose—can be prescribed safely to patients with NSAID-induced asthma. According to our results, most people with adverse cutaneous reactions from NSAIDs can tolerate a high dose of rofecoxib.
Accepted for publication 13 August 2002
Allergy 2002: 57:1214-1215
Copyright © Blackwell Munksgaard 2002