Risk factors for positive paracetamol drug provocation testing and procedure optimization

Blood pressure measurements could be reduced in number during the drug provocation test

“…However, learned societies only set a frame for DPT performance and do not make specific recommendations about the type and rhythm of these measurements 1,3,4 . In our centre, data‐driven DPT is performed in 2–7 step dosing, depending on the drug classes, with time increments of 30 or 60 min (up to 3 h for certain nonsteroidal anti‐inflammatory drugs [NSAID]) 5–8 . The beta‐lactams (BL) pattern is generally applied to DPTs for other drugs.…”

“…Empirically, we considered the measurement of blood pressure (BP) and pulse as mandatory and required before starting the DPT, before every incremental dose and at any time during the DPT if symptoms of a DHR occurred. For patients with clinical histories of immediate non‐severe reactions, up to 25% of them may develop anaphylaxis during DPT 5–8 . A recent meta‐analysis of severe reactions during DPT 9 has found that the risk of anaphylactic reaction rises to one in each 345 DPT, and 22 DPT in patients reporting immediate reactions, and history of anaphylaxis, respectively.…”

“…Based on this and previous analyses of reactivity patterns and severity during DPT for different drug classes, we propose criteria to reduce the frequency of BP measurements during DPT, according to risk stratification based on patient clinical history and drug class. The risk of eliciting anaphylaxis during DPT is increased if the index clinical history is anaphylaxis, regardless of the drug class 5–8 . Moreover, patients with a history of anaphylaxis are also at risk for anaphylaxis during ST to BL 10 .…”

“…Therefore, clinical history could be classified into three categories: immediate severe (high risk), immediate non‐severe (low risk) and non‐immediate non‐severe (low risk) reactions (ie severe non‐immediate reactions being classical contraindications to DPT) 3 . Regarding drug class, we based our risk stratification on previous studies tackling patterns of DPT reactions to BL, NSAIDs, paracetamol and quinolones showing that the frequency of anaphylaxis elicited by DPT was 15%, 10%, 25% and 20%, respectively 5–8 . Of note, we systematically focus on testing culprit drugs (rather than directly alternatives) (87.9% for BL, 100% for paracetamol, 91.8% for quinolones), except for NSAIDs (where cross‐intolerance must be taken into account) 5–8 .…”

“…Regarding drug class, we based our risk stratification on previous studies tackling patterns of DPT reactions to BL, NSAIDs, paracetamol and quinolones showing that the frequency of anaphylaxis elicited by DPT was 15%, 10%, 25% and 20%, respectively 5–8 . Of note, we systematically focus on testing culprit drugs (rather than directly alternatives) (87.9% for BL, 100% for paracetamol, 91.8% for quinolones), except for NSAIDs (where cross‐intolerance must be taken into account) 5–8 . For NSAIDs, the cross‐intolerance reactions are a typical clinical presentation and for such an index reaction, 90% of the positive DPT are benign cutaneous reactions 7 .…”