CAST® Allergens for CAST® ELISA Flow CAST® Drug Allergens A Commitment to Diagnostics A Allergen booklet Drugs Release date: 2021-08-02 BÜHLMANN CAST® ALLERGENS 2 / 44 Release date: 2021-08-02 Content - Inhalt - Contenu- Contenuto - Contenido Introduction 3 BAG2-CERY Erythromycin 26 Literature 13 BAG2-CRIF Rifampicin 26 ACE inhibitors 14 Antiseptics 27 BAG2-CRAM Ramipril 14 BAG2-CCHX Chlorhexidine 27 Analgesics 15 Beta Blockers 28 BAG2-C51 Lys-Aspirin 15 BAG2-CBIS Bisoprolol 28 BAG2-C52 Diclofenac 15 BAG2-CMET Metoprolol 28 BAG2-C53 Ibuprofen 15 Contrast Media 29 BAG2-C54 Indomethacin 16 BAG2-CIOBI Iobitridol 29 BAG2-C55 Acetaminophen 16 BAG2-CIODI Iodixanol 29 BAG2-C56 Mefenamic Acid 16 BAG2-CIOHE Iohexol 29 BAG2-C57 Phenylbutazone 17 BAG2-CIOME Iomeprol 30 BAG2-C58 Propyphenazone 17 BAG2-CIOPA Iopamidol 30 BAG2-C59 Dipyrone / Metamizole 17 BAG2-CIOPR Iopromide 30 BAG2-CNAP Naproxen 18 BAG2-CIOXA Ioxaglate 31 BAG2-C114 Salicylic acid 18 Local Anesthetics 32 BAG2-CTRA Tramadol 18 BAG2-CART Articaine 32 Antibiotics 19 BAG2-CBUP Bupivacaine 32 BAG2-C1 Penicillin G 19 BAG2-CMEP Mepivacaine 32 BAG2-C11 Benzylpenicilloyl-Polylysine (PPL) 19 BAG2-CLID Lidocaine 33 BAG2-C12 Minor Determinant Mix (MDM) 19 Myorelaxants 34 BAG2-C2 Penicillin V 20 BAG2-CATR Atracurium 34 BAG2-C3 Cephalosporin C 20 BAG2-CCAT Cis-Atracurium 34 BAG2-C31 Cefamandole 20 BAG2-CMIV Mivacurium 34 BAG2-C32 Cefazoline 21 BAG2-CPAN Pancuronium 35 BAG2-C33 Cefuroxime 21 BAG2-CPRO Propofol 35 BAG2-C34 Cefaclor 21 BAG2-CROC Rocuronium 35 BAG2-C35 Ceftriaxone 22 BAG2-CSUX Suxamethonium 36 BAG2-C36 Levofloxacin 22 BAG2-CVEC Vecuronium 36 BAG2-C61 Sulfamethoxazole 22 BAG2-CNBX Neuromuscular Blockers Mix 37 BAG2-C62 Trimethoprim 23 Proton Pump Inhibitors 38 BAG2-C75 Tetracycline 23 BAG2-COME Omeprazole 38 BAG2-C76 Doxycycline 23 BAG2-CESO Esomeprazole 38 BAG2-C81 Ciprofloxacine 24 BAG2-CPANT Pantoprazole 38 BAG2-C82 Moxifloxacin 24 BAG2-CLAN Lansoprazole 39 BAG2-C203 Ampicillin 24 Excipients BAG2-C204 Amoxicillin 25 BAG2-CPEG PEG-4000 41 BAG2-CCLA Clarithromycin 25 BAG2-CPEG2 PEG-2000 41 BAG2-CCLAX Clavulanic Acid Amox 25 BAG2-CPEG3 DMG PEG-2000 41 BAG2-CCLIN Clindamycin 26 BÜHLMANN CAST® ALLERGENS 3 / 44 Release date: 2021-08-02 Introduction Intended Use Optimal time period for stimulation tests BÜHLMANN CAST® Allergens are optimized for in vitro For optimal results, CAST® assays should be run between Basophil Activation using BÜHLMANN CAST® assays: 3 and 12 weeks after an allergic reaction to the presumed CAST® ELISA (EK-CAST) and Flow CAST® (FK-CCR). allergen [Lit.8], although specific basophil reaction is often CAST® Allergens are not included in BÜHLMANN CAST® being persistent over a longer time period. assays. They are provided upon request. Refer to the aller- Blood samples must be drawn for CAST® assays before gen list. carrying out a skin test or in vivo provocation with the presumed allergen as in vivo exposure to an allergen can Instruction for Use cause an activation of the leucocytes. The following instructions are intended for the following groups of drug allergens and mixes of them (refer to TOC Limitations page 3). A negative CAST® assay result for a specific allergen does • ACE Inhibitors not exclude potential (even serious) clinical symptoms. Individuals who developed „allergic“ reactions towards • Analgesics protein or drug allergens in the past and whose CAST® • Antibiotics assay was negative, should thus be verified with additional • Antiseptics methods like the in vivo provocation or skin test before a drug or allergen is administered. • Beta Blockers • Contrast Media Concentrations and cut-off Concentrations and cut-off of these allergen groups were Local Anesthetics • optimized regarding maximum specificity and sensitivity. • Myorelaxants Concentrations and cut-offs of individual allergens are reported in the specifications of the allergens (refer to TOC • Proton Pump Inhibitors (PPI) page 3). • Excipients For Flow CAST®, BÜHLMANN recommends the applica- CAST® drug allergens are delivered lyophilized. Before tion of the stimulation index (SI) as an additional diagnos- usage in CAST® assays, they are to be reconstituted with tic criterion. The SI is defined as the ratio of allergen test specific Stimulation Buffer: CAST® ELISA: B-CAST-STB specific basophil activation and background activation. and Flow CAST®: B-CCR-STB. Remarks: • Add 250 µL Stimulation Buffer into the vial and vortex until the lyophilized material has completely dissolved. • In order to apply allergen specific cut-offs, QC criteria published in the CAST® instructions must be fulfilled. • For some allergens we recommend an additional dilution with Stimulation Buffer (refer to the paragraph • Cut-offs should serve only as recommendations. Clini- „Additional dilutions“ in the allergen specifications). cally defined cut-offs should be established by each laboratory or through clinical studies. • E.g. an „ additional dilution” of 1:5 is carried out by adding 160 µL Stimulation Buffer to 40 µL allergen Recommendations how to use CAST® assays in the solution. diagnosis of drug allergies • For stimulation of cells, use these dilutions according The diagnosis of drug allergies is a complex matter includ- to the respective CAST® IFU. ing heterogeneous symptoms and a diverse pathophysi- ology. Thus the following recommendations should be Remark: Some individuals react positive either at high or considered when using CAST® assays in order to diagnose at low allergen concentrations, whereas others react drug allergies. These recommendations should be consid- positive over a broad range of concentration. ered only as general guidelines. Storage and Stability Unopened CAST® Allergens are to be stored at the tempera- ture specified on the label until the expiration date. Important: Reconstituted or diluted allergens must not be stored and used again! BÜHLMANN CAST® ALLERGENS 4 / 44 Release date: 2021-08-02 Clinical pictures, justifying the application of CAST® assays Direct “allergic” reactions in vivo after exposure to drugs or chemicals can either be IgE or non-IgE mediated (pseudo-allergic reactions) stimulation of effector cells (e.g. basophils, mast cells, and eosinophils). CAST® assays may serve as a model for the above mentioned reactions by which the individuals’ leucocytes are stimu- lated in vitro. As for CAST® assays pure allergens and a defined but artificial buffer system are applied, the method can only serve as a simplified model of the real in vivo conditions. CAST® assays were optimized for the detection of immediate type allergic reactions (Type I) and pseudo allergic reactions. CAST® assays are not applicable for the diagnosis of delayed type allergies (e.g. Type IV reactions). Thus, these assays should be applied only for immediate type allergic reactions, especially if one of the following symptoms is detected: • Anaphylactic or anaphylactoide reactions • Rhino conjunctivitis • Asthma bronchiale • Urticaria / Angioedema • Gastrointestinal reactions Clinical pictures that do not justify the application of CAST® assays CAST® assays should not be used for the diagnosis of T-cell mediated reactions. Based on the pathogenetical mechanism it is not recommended using CAST® assays routinely for the following patient groups: • Maculopapular and pustular exanthema • Vasculitis • Allergic contact dermatitis • Bullous exanthemas such as Stevens-Johnsons Syndrome and Lyell’s disease BÜHLMANN CAST® ALLERGENS 5 / 44 Release date: 2021-08-02 Einführung Anwendungszweck gelagert werden. Die BÜHLMANN CAST® Allergene sind optimiert für die in vitro Leukozyten Stimulation in den BÜHLMANN CAST® Tests: CAST® ELISA (EK-CAST) und Flow CAST® Wichtig: Aufgelöste oder verdünnte Allergene sollen nicht (FK-CCR). aufbewahrt und wieder verwendet werden! CAST® Allergene sind als einzelne Reagenzien erhältlich Zeitpunkt der Patientenmessung und sind kein Bestandteil der CAST® Test Kits. Der optimale Zeitraum zur Durchführung eines CAST® Tests liegt zwischen 3 und 12 Wochen nach einer aller- Gebrauchsanweisung gischen Reaktion auf ein vermutetes Allergen [Lit.8]. Dies, Die nachfolgende Anleitung gilt für die folgenden Medika- obwohl die spezifische Reaktivität der basophilen Zellen menten-Allergene sowie deren Allergengemische (siehe oft auch über einen noch längeren Zeitraum erhalten Inhaltsverzeichnis auf Seite 3): bleibt. • ACE-Hemmer (ACE Inhibitors) Die Blutproben für die CAST® Tests müssen abgenommen • Schmerzmittel (Analgesics) werden, bevor ein Hauttest oder eine in vivo Provokation mit dem verdächtigen Allergen durchgeführt wurde. Die in • Antibiotika (Antibiotics) vivo Exposition gegenüber einem Allergen kann eine • Antiseptika (Antiseptics) generelle Aktivierung der Patientenleukozyten zur Folge haben • Betablocker (Beta Blockers) Einschränkungen • Röntgenkontrastmittel (Contrast Media) Ein negatives CAST® Test Resultat für ein spezifisches • Lokalanästhetika (Local Anesthetics) Allergen schliesst die Möglichkeit einer (auch schweren) • Muskelrelaxantien (Myorelaxants) klinischen Reaktion beim Patienten nicht aus. Patienten, • Protonenpumpeninhibitoren (PPI) die früher „allergische“ Reaktionen gegenüber Protein- oder Medikamenten-Allergenen gezeigt haben und die ein • Hilfsstoffe (Excipients) negatives CAST® Test Resultat aufweisen, sollten deswe- CAST® Medikamenten-Allergene werden in getrockneter gen, wenn möglich, mit weiteren Methoden wie in vivo Form geliefert. Vor dem Gebrauch der Allergene in den Provokation oder Hauttestung getestet werden, bevor ein CAST® Tests werden diese mit dem