Original Paper Int Arch Allergy Immunol 2002;129:242–247 DOI: 10.1159/000066777 Single-Dose Oral Tolerance Test with Alternative Compounds for the Management of Adverse Reactions to Drugs Giovanni Passalacqua Manlio Milanese Marcello Mincarini Giorgio Ciprandi Laura Guerra Antonio Scordamaglia Giorgio Walter Canonica Allergy and Respiratory Diseases, DIMI, Department of Internal Medicine, Genoa University, Genoa, Italy Received: December 27, 2001 Accepted after revision: July 31, 2002 Correspondence to: Dr. Giovanni Passalacqua Allergy and Respiratory Diseases – DIMI, Padiglione Maragliano Largo R.Benzi 10, I–16132 Genoa (Italy) Tel. +39 010 3538908, Fax +39 010 3538904 E-Mail giovanni.passalacqua@hsanmartino.liguria.it ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2002 S. Karger AG, Basel 1018–2438/02/1293–0242$18.50/0 Accessible online at: www.karger.com/iaa Key Words Adverse reactions to drugs W Oral tolerance test Abstract Background: Adverse reactions to drugs are common in the clinical practice. Many outpatients are frequently referred to allergists in order to determine which drugs they can safely take in the future. Objective: We set up an oral single-dose tolerance test procedure to find out for each patient one or more alternative drugs that can be taken when needed. M ethods: 452 outpatients (130 male, 322 female) with well-documented reactions (urti- caria/angioedema, respiratory symptoms, laryngeal ede- ma, anaphylaxis, exfoliative skin diseases) underwent the challenge. All tests were preceded by a single-blind placebo: if a reaction occurred, a second placebo was administered. Otherwise, a single dose (1/10 of the thera- peutic one) of an alternative drug was given blindly and the patient was then observed for 6 h. The drugs used were different in structure from those suspected of hav- ing caused the adverse reaction. The patients were fol- lowed up at 4- to 6-month intervals, in order to detect any reaction that may have occurred with the tested drugs. Results: 98 patients (89 women) had untoward reactions after the first placebo and 34 out of them reacted to the second placebo, too. During challenges the reaction rate ranged between 4.6 and 9.0%; these reactions were easi- ly managed and none of them was severe. We followed up 407 patients: 87.2% of them were able to use one or more of the suggested drugs without reactions, 9.3% did not take the drugs and only 3.5% reported reactions to the previously tested drugs. Conclusion: The challenge procedure proved to be a simple tool for managing patients with adverse reactions to drugs. Its safety and reliability were validated by a long-term follow-up. Copyright © 2002 S. Karger AG, Basel Introduction All drugs, even if properly used, may provoke un- wanted events, which represent a challenge for physicians. About three quarters of untoward effects are related to the chemical and/or pharmacological properties of the drugs themselves; therefore, they are usually predictable and avoidable [1]. These reactions include overdosing, drug interaction, side effects and indirect effects. Unexpected reactions, unrelated to the mechanism of action of a given drug, may also occur; these include idiosyncrasy (e.g. enzymatic deficiencies), intolerance and immune-me- diated reactions or hypersensitivity [1–3]. For certain drugs (e.g. ß-lactams and muscle relaxants) the IgE- mediated mechanism has been clearly documented [4–6].