Outcomes and safety of drug provocation tests

Abstract

Drug provocation tests (DPTs) are considered the gold standard for identifying adverse drug reactions (ADRs). The aim of this study was to analyze DPT results and discuss severe systemic reactions associated with them. This was a retrospective analysis of 500 patients with ADRs who sought treatment and were submitted to DPTs when indicated between 2006 and 2010. We performed DPTs according to the European Network for Drug Allergy recommendations. Single-blind, placebo-controlled DPTs were performed with antibiotics, local anesthetics, and nonsteroidal anti-inflammatory drugs, as well as with other drugs. Patient characteristics, DPT results, and reactions were analyzed. The sample comprised 198 patients (80.8% of whom were female patients) submitted to 243 DPTs. Ages ranged from 9 to 84 years (mean, 39.9 years). The 243 DPTs were performed with local anesthetics (n = 93), antibiotics (n = 19), acetaminophen (n = 44), benzydamine (n = 33), COX-2 inhibitors (n = 26), dipyrone (n = 7), aspirin (n = 4), or other drugs (n = 17). The results of 4 tests (1.6%) were inconclusive, whereas those of 10 (4.1%) revealed positive reactions to antibiotics (2/19), COX-2 inhibitors (2/26), acetaminophen (3/44), and local anesthetics (3/93). Two severe reactions were observed: cephalexin-induced anaphylactic shock and bupivacaine-induced anaphylaxis without shock. Four patients (2.0%) reacted to the placebo before administration of the drug. Drug provocation tests are safe for use in clinical practice but they should be placebo-controlled and should be performed under the supervision of an allergist. To confirm a presumptive diagnosis and to manage allergies appropriately, it is crucial to perform DPTs.

Safety and Outcomes of Test Doses for the Evaluation of Adverse Drug Reactions: A 5-Year Retrospective Review

“…The ADR rates of 11% for test doses and 12% for multistep challenges in our study fall between rates of 4.1% and 16% reported in prior studies. 9,10 Unlike other studies, no anaphylactic reactions occurred with test doses or multistep challenges, which underlies the importance of careful review and evaluation of a patient's drug allergy history before performing test doses or challenges. 10 Our findings, therefore, demonstrated that test doses are safe for evaluation of ADRs and that multistep challenges do not confer additional safety.…”

“…9,10 Unlike other studies, no anaphylactic reactions occurred with test doses or multistep challenges, which underlies the importance of careful review and evaluation of a patient's drug allergy history before performing test doses or challenges. 10 Our findings, therefore, demonstrated that test doses are safe for evaluation of ADRs and that multistep challenges do not confer additional safety. Advantages of 1-or 2-step test doses over multistep challenges include the lack of concern for induction of tolerance or desensitization; the requirement for fewer resources, such as staffing and time; and the ability for inpatients to reach therapeutic dosing more rapidly.…”

“…One prior study demonstrated a 16% subjective reaction rate and 0.8% true reaction rate, whereas another study reported a reaction rate of 4.1%, which included 2 anaphylactic reactions. 9,10 Graded challenges are not recommended if the patient's history was consistent with a severe non-IgEemediated reaction, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis, hepatitis, or hemolytic anemia. 11,12 Despite the widespread use of graded challenges for the evaluation of ADRs, there are no evidence-based guidelines that delineate the optimal number of steps.…”

Identifying Allergic Drug Reactions Through Placebo-Controlled Graded Challenges

“…9,12-16 One study reported a 16% subjective reaction rate with a 0.8% true reaction rate, 12 whereas other studies reported an overall reaction rate between 4.1% and 12%. 9,13,17 Despite the extensive use of graded challenges for the evaluation of ADRs, evidence-based guidelines regarding optimal protocols are lacking. 8 A study published in 1992 of patients with historical penicillin reactions and subsequent negative skin testing used a 2-step active challenge composed of a subcutaneous test dose of 5 mg of penicillin followed by a full therapeutic dose.…”

“…17 Other challenges reported in the literature range from Abbreviations used ADR-Allergic drug reaction NSAID-Nonsteroidal anti-inflammatory drug administration of single therapeutic doses to multiple doses over several days with variable use of placebo. 9,[12][13][14][15][16]18 Concern exists that challenges composed of more than 4 steps may lead to an induction of tolerance. 6 A recent noneplacebo-controlled study demonstrated that a 2-step graded challenge is as safe as a 3-or 4-step graded challenge with a reaction rate of 11% versus 12%, respectively.…”