Background: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly observed in clinical practice, particularly among patients with chronic urticaria or asthma. The identification of a safe and reliable alternative is a frequent problem for both general practitioners and allergists. Methods: We assessed 120 patients (83 women and 37 men) who had experienced adverse reactions to one or more NSAIDs; 64 (53.3%) of them had reacted to only one NSAID (single reactors) and 56 (46.7%) to multiple NSAIDs (multiple reactors). Among our subjects, 76.7% reported cutaneous reactions, 8.3% respiratory symptoms, 10.8% both cutaneous and respiratory symptoms, and 4.2% anaphylaxis. All patients were subjected to a single-blind, placebo-controlled oral challenge with two different doses of celecoxib (50 + 150 mg 1 h later = cumulative dose of 200 mg). Results: None of the patients reacted to the placebo and only one (0.8%) suffered a reaction (urticaria) after the second dose of celecoxib. Conclusions: Celecoxib showed a 98.9% rate of tolerability in the 92 patients with exclusively cutaneous reactions and was well tolerated by all 28 subjects with NSAID-related respiratory or anaphylactic symptoms.

Keywords:
Celecoxib, Challenges, Hypersensitivity, Nonsteroidal anti-inflammatory drugs
1.
Naldi L, Conforti A, Venegoni M, Troncon MG, Caputi A, Ghiotto E, Cocci A, Moretti U, Velo G, Leone R: Cutaneous reactions to drugs. An analysis of spontaneous reports in four Italian regions. Br J Clin Pharmacol 1999;48:839–846.
2.
Namazy JA, Simon RA: Sensitivity to nonsteroidal anti-inflammatory drugs. Ann Allergy Asthma Immunol 2002;89:542–550.
3.
Stevenson DD: Diagnosis, prevention, and treatment of adverse reactions to aspirin and nonsteroidal anti-inflammatory drugs. J Allergy Clin Immunol 1984;74:617–622.
4.
Szczeklik A: Adverse reactions to aspirin and nonsteroidal anti-inflammatory drugs. Ann Allergy 1987;59:113–118.
5.
Kowalski ML, Woszczek G, Bienkiewicz B, Mis M: Association of pyrazolone drug hypersensitivity with HLA-DQ and DR antigens. Clin Exp Allergy 1998;28:1153–1158.
6.
Himly M, Jahn-Schmid B, Pittertschatscher K, Bohle B, Grubmayr K, Ferreira F, Ebner H, Ebner C: IgE-mediated immediate-type hypersensitivity to the pyrazolone drug propyphenazone. J Allergy Clin Immunol 2003;111:882–888.
7.
Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971;231:232–235.
8.
Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G: Relationship of inhibition of prostaglandin biosynthesis by analgesics to asthma attacks in aspirin-sensitive patients. Br Med J 1975;i:67–69.
9.
Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G: Clinical patterns of hypersensitivity to nonsteroidal anti-inflammatory drugs and their pathogenesis. J Allergy Clin Immunol 1977;60:276–284.
10.
Mastalerz L, Malgorzta S, Sanak M, Szczeklik A: Hypersensitivity to aspirin: Common eicosanoid alterations in urticaria and asthma. J Allergy Clin Immunol 2004;113:771–775.
11.
Carmona MJ, Blanca M, Garcia A, Fernandez S, Burgos F, Miranda A, Vega JM, Garcia J: Intolerance to piroxicam in patients with adverse reactions to nonsteroidal antiinflammatory drugs. J Allergy Clin Immunol 1992;90:873–879.
12.
Szczeklik A, Stevenson DD: Aspirin-induced asthma: Advances in pathogenesis, diagnosis, and management. J Allergy Clin Immunol 2003;111:913–921.
13.
Zembowicz A, Mastalerz L, Setkowicz M, Radziszewski W, Szczeklik A: Safety of cyclooxygenase 2 inhibitors and increased leukotriene synthesis in chronic idiopathic urticaria with sensitivity to nonsteroidal anti-inflammatory drugs. Arch Dermatol 2003;139:1577–1582.
14.
Graham GG, Scott KF: Mechanisms of action of paracetamol and related analgesics. Inflammopharmacology 2003;11:401–413.
15.
Settipane RA, Schrank PJ, Simon RA, Mathison DA, Christiansen SC, Stevenson DD: Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects. J Allergy Clin Immunol 1995;96:480–485.
16.
Quaratino D, Romano A, Papa G, Di Fonso M, Giuffreda F, Purello D’Ambrosio F, Venuti A: Long-term tolerability of nimesulide and acetaminophen in nonsteroidal anti-inflammatory drug-intolerant patients. Ann Allergy Asthma Immunol 1997;79:47–50.
17.
Quaratino D, Romano A, Di Fonso M, Papa G, Perrone MR, Purello D’Ambrosio F, Venuti A: Tolerability of meloxicam in patients with histories of adverse reactions to nonsteroidal anti-inflammatory drugs. Ann Allergy Asthma Immunol 2000;84:613–617.
18.
Stevenson DD, Simon RA, Christensen SC: Lack of cross-reactivity between selective COX-2 inhibitors and aspirin (ASA) in ASA sensitive asthmatic subjects. J Allergy Clin Immunol 2000;105:S273.
19.
Yoshida S, Ishizaki Y, Onuma K, Shoji T, Nakagawa H, Amayasu H: Selective cyclo-oxygenase 2 inhibitor in patients with aspirin-induced asthma. J Allergy Clin Immunol 2000;106:1201–1202.
20.
Sánchez-Borges M, Capriles-Hulett A, Caballero-Fonseca F, Pérez CR: Tolerability to new COX-2 inhibitors in NSAID-sensitive patients with cutaneous reactions. Ann Allergy Asthma Immunol 2001;87:201–204.
21.
Dahlén 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;344:142.
22.
García-Rodríguez RM, Hinojosa M, Camacho-Garrido E, Berges Gimeno P, Martín-García C: Celecoxib, safe in NSAID intolerance. Allergy 2002;57:1085–1086.
23.
Woessner KM, Simon RA, Stevenson DD: The safety of celecoxib in patients with aspirin-sensitive asthma. Arthritis Rheum 2002;46:2201–2206.
24.
Kruse R, Ruzicka T, Grewe M: Intolerance reactions due to the selective cyclooxygenase type II inhibitors rofecoxib and celecoxib. Acta Derm Venereol 2003;83:183–185.
25.
Gyllfors P, Bochenek G, Overholt J, Drupka D, Kumlin M, Sheller J, Nizankowska E, Isakson PC, Mejza F, Lefkowith JB, Dahlén SE, Szczeklik A, Murray JJ, Dahlén B: Biochemical and clinical evidence that aspirin-intolerant asthmatic subjects tolerate the cyclooxygenase 2-selective analgetic drug celecoxib. J Allergy Clin Immunol 2003;111:1116–1121.
26.
Martin-Garcia C, Hinojosa M, Berges P, Camacho E, Garcia-Rodriguez R, Alfaya T: Celecoxib, a highly selective COX-2 inhibitor, is safe in aspirin-induced asthma patients. J Investig Allergol Clin Immunol 2003;13:20–25.
27.
Valero A, Enrique E, Baltasar M, Cistero A, Marti E, Picado C: Celecoxib in NSAID-induced cutaneous and respiratory adverse reactions (in Spanish). Med Clin (Barc) 2003;121:695–696.
28.
Ahlbach S, Usadel KH, Kaufmann R, Boehncke WH: The selective cyclooxygenase-2 inhibitor celecoxib is a safe alternative in patients with pseudo-allergic reactions to nonsteroidal anti-inflammatory drugs (in German). Med Klin (Munich) 2003;98:242–244.
29.
Senna G, Bilò MB, Antonicelli L, Schiappoli M, Crivellaro MA, Bonadonna P, Dama AR: Tolerability of three selective cyclo-oxygenase-2 inhibitors, meloxicam, celecoxib and rofecoxib in NSAID-sensitive patients. Allergol Immunol (Paris) 2004;36:215–218.
30.
Quiralte J, Delgado J, Sáenz de San Pedro B, López-Pascual E, Nieto MA, Ortega N, Florido JF, Conde J: Safety of the new selective cyclooxygenase type 2 inhibitors rofecoxib and celecoxib in patients with anaphylactoid reactions to nonsteroidal anti-inflammatory drugs. Ann Allergy Asthma Immunol 2004;93:360–364.
31.
Johansson SGO, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela T, Kowalski ML, Mygind N, Ring J, van Cauwenberge P, van Hage-Hamsten M, Wüthrich B; EAACI (the European Academy of Allergology and Clinical Immunology) Nomenclature Task Force: A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 2001;56:813–824.
32.
Papa G, Romano A, Del Bono A, Quaratino D, Di Fonso M, Pocobelli D, Giuffreda F, Venuti A: Floctafenine: A valid alternative in patients with adverse reactions to non steroidal anti-inflammatory drugs. Ann Allergy Asthma Immunol 1997;78:74–78.
33.
Perrone MR, Artesani MC, Viola M, Gaeta F, Caringi M, Quaratino D, Romano A: Tolerability of rofecoxib in patients with adverse reactions to nonsteroidal anti-inflammatory drugs: A study of 216 patients and literature review. Int Arch Allergy Immunol 2003;132:82–86.
34.
Nizankowska E, Bestyńska-Krypel A, Ćmiel A, Szczeklik A: Oral and bronchial provocation tests with aspirin for diagnosis of aspirin-induced asthma. Eur Respir J 2000;15:863–869.
35.
Stevenson DD, Sánchez-Borges M, Szczeklik A: Classification of allergic and pseudoallergic reactions to drugs that inhibit cyclooxygenase enzymes. Ann Allergy Asthma Immunol 2001;87:177–180.
36.
Ispano M, Fontana A, Scibilia J, Ortolani C: Oral challenge with alternative nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen in patients intolerant to these agents. Drugs 1993;46(suppl 1):253–256.
37.
Passalacqua G, Milanese M, Mincarini M, Ciprandi G, Guerra L, Scordamaglia A, Canonica GW: Single-dose oral tolerance test with alternative compounds for the management of adverse reactions to drugs. Int Arch Allergy Immunol 2002;129:242–247.
38.
Aberer W, Bircher A, Romano A, Blanca M, Campi P, Fernandez J, Brockow K, Pichler WJ, Demoly P; European Network for Drug Allergy (ENDA); EAACI Interest Group on Drug Hypersensitivity: Drug provocation testing in the diagnosis of drug hypersensitivity reactions: General considerations. Allergy 2003;58:854–863.
39.
Grob M, Pichler WJ, Wüthrich B: Anaphylaxis to celecoxib. Allergy 2002;57:264–265.
40.
Gagnon R, Julien M, Gold P: Selective celecoxib-associated anaphylactoid reaction. J Allergy Clin Immunol 2003;111:1404–1405.
41.
SIAIC Memorandum on drug allergy/intolerance diagnosis. Ital J Allergy Clin Immunol 1998;8:568–595.
42.
Delaney JC: The diagnosis of aspirin idiosyncrasy by analgesic challenge. Clin Allergy 1976;6:177–181.
43.
Falliers CJ: Acetaminophen and aspirin challenges in subgroups of asthmatics. J Asthma 1983;20:39–49.
44.
West PM, Fernandez C: Safety of COX-2 inhibitors in asthma patients with aspirin hypersensitivity. Ann Pharmacother 2003;37:1497–1501.
© 2005 S. Karger AG, Basel
2005
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.