• aspirin intolerance;
  • azapropazone;
  • nonsteroidal anti-inflammatory drug (NSAID)

Patients with aspirin intolerance often react also to many nonsteroidal anti-inflammatory drugs (NSAID) such as indomethacin or diclophenac. The reactions do not depend on an allergic mechanism but are related to the pharmacologic action of the NSAID. The inhibitory effect on cyclooxygenase activity leads to an imbalance of prostanoids. In the respiratory tract, this provokes asthma attacks. NSAID which do not have an inhibitory influence on cyclooxygenase activity (paracetamol, salicylamide) are usually well tolerated by these patients (1).

Azapropazone is a moderately potent anti-inflammatory analgesic agent in comparison with standard drugs, such as aspirin, indomethacin, and phenylbutazone (2). It is known to have only a weak anti-cyclooxygenase-1 and anti-cyclooxygenase-2 activity (3). Its safety in patients with immediate-type hypersensitivity to pyrazolones has already been demonstrated (4). We investigated the tolerance of this drug in patients with aspirin intolerance.

Thirty-four patients with documented aspirin intolerance were included in the study, whereas patients with IgE-mediated hypersensitivity to pyrazolones were excluded. The patients suffered from urticaria and/or angioedema after intake of aspirin. The diagnosis was based on an unequivocal case history and a negative prick and intradermal reaction to various analgesics including acetylsalicylic acid, pyrazolones, and azapropazone. The test concentration of each drug was 0.1%. Oral challenge tests with azapropazone were performed with a maximum single dose of 600 mg, which is the common single dose. The cumulative dose was 1060 mg (Table 1). The time interval between the dosages was 1 h. In case of doubtful reactions, the oral challenge was repeated with double-blind placebo controls.

Table 1.  Azapropazone in patients with aspirin intolerance
Number of study patientsMaximum single dose of azapropazoneCumulative dose of azapropazoneAdverse reactions after open challengeAdverse reactions after double-blind, placebo-controlled challenge
34600 mg1060 mg10

The skin tests were completely negative in all patients. In 33 out of 34 patients, the oral administration of azapropazone in a cumulative dose of 1060 mg did not cause any adverse reaction. One patient experienced pruritus and redness of the neck 4 h after the 600-mg dosage, but this could not be confirmed in the double-blind, placebo-controlled rechallenge.

The result of this study is unequivocal, since none of the patients with aspirin intolerance showed any adverse reaction to azapropazone after placebo-controlled challenge. At first glance, this result might be surprising since azapropazone has a pyrazolidine moiety in its molecule, and it resembles phenylbutazone structurally (2). Nonetheless, it has only a weak anticyclooxygenase activity in vitro. Obviously, this inhibitory effect is negligible in vivo. Our study confirms the result of a smaller study in which the tolerance of azapropazone in 12 patients with aspirin-induced asthma was demonstrated (5).

The fact that cyclooxygenase inhibition is not a major effect of azapropazone is necessary for the good tolerance of the drug in patients with aspirin intolerance. Azapropazone has a more potent anti-inflammatory and analgesic effect than paracetamol (2). Therefore, azapropazone has a broader spectrum of indications than paracetamol. In addition, its general toxicity is relatively low.

In conclusion, azapropazone can be added to the list of NSAID that can be prescribed with little risk for patients with aspirin intolerance. From the allergologic point of view, this drug is as safe as paracetamol.


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  2. References
  • 1
    Szczeklik A. Analgesics, allergy and asthma. Drugs 1986;32 Suppl 4:148 163
  • 2
    Walker FS. Azapropazone and related benzotriazines In: RainsfordKD, editor. Anti-inflammatory and anti-rheumatic drugs. Vol. II. Boca Raton, FL: CRC Press, 1985:1 32
  • 3
    Riendeau D, Charleson S, Cromlish W, Mancini JA, Wong E, Guay J. Comparison of the cyclooxygenase-1 inhibitory properties of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, using sensitive microsomal and platelet assays. Can J Physiol Pharmacol 1997;75:1088 1095
  • 4
    Nizankowska E, Bochenek G, Czerniawska-mysik G, Szczeklik A. Tolerance of the pyrazolidine derivative azapropazone in hypersensitivity to pyrazolone drugs. Allergo J 1994;3:320 326
  • 5
    Nizankowska E, Czerniawska-mysik G, Bochenek G, Szczeklik A. Tolerance of azapropazone in hypersensitivity to pyrazolones and in aspirin-induced asthma [Abstract]. Eur J Allergy Clin Immunol 1992;47 Suppl 12:22
  1. Azapropazone is a safe alternative in patients with aspirin intolerance.