Table 1. Classification of Type B^a adverse reactions to therapeutic agents.

Hypersensitivity (Immune; Allergic)			Non-Allergic Sensitivities (Non-immune)
Hypersensitivity Typeb	Mediated by	Examples	Subtypes	Examples
Type Ic	IgE antibodies	Penicillins; cephalosporins; neuromuscular blockers; mAbs; pyrazolones; proton pump inhibitors; L-asparaginase	Pseudo- Allergyd	Most reactions to NSAIDs;e Direct mast cell degranulation (neuromuscular blockers; opioids; contrast media; vancomycin)
Type IIf	IgG/IgM cytotoxic reactions	Penicillins; cephalosporins; quinine; quinidine; sulfonamides; thiouracil; oxaliplatin; mAbs; gold salts; NSAIDs; procainamide; ticlopidine	Idiosyncratic Reactionsg	Halothane hepatitis; malignant hypothermia; drug induced hemolytic anemia in Glu-6-PO4 dehydrogenase-deficient individuals (anti-malarials, sulfonamides, dapsone)
Type IIIh	IgG/IgM immune complexes	Penicillins; cephalosporins; sulfonamides; allopurinol; NSAIDs; carbamazepine; mAbs; tamoxifen; oxaliplatin	Intolerances	? some reactions to contrast media and NSAIDsi Tinnitus induced by small doses of aspirin
Type IVj,k	T cells	NSAIDs; penicillins; local anesthetics; hydroxychloroquine; anti-convulsants (eg carbamazepine); dapsone; mAbs; tamoxifen

Note that mAbs can provoke all 4 types of hypersensitivity reactions. ^aSo-called ‘Bizarre’ reactions that are uncommon unpredictable, rarely dose dependent and unrelated to agent’s pharmacologic action. Relative to other categories of adverse reactions, these reactions show high mortality. ^bAccording to the definition and classification of Gell and Coombs (see ref.5). ^cManifest as anaphylaxis, bronchospasm, cardiovascular collapse, urticaria, angioedema. ^dSome reactions closely resemble true Type I reactions and are termed 'anaphylactoid'. ^eNSAIDs, non-steroidal anti-inflammatory drugs. ^fE.g. drug-induced hemolytic anemia, immune thrombocytopenia, immune form of agranulocytosis. ^gMay be unrelated or related to dose. Uncommon, unpredictable, unrelated to drug’s pharmacologic action. ^hE.g. serum sickness-like reactions, drug-induced vasculitis. ⁱSome reactions to NSAIDs and contrast media are clearly not hypersensitivity responses or pseudoallergic or idiosyncratic in nature. ^jE.g. allergic contact dermatitis, psoriasis, maculopapular exanthema, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, erythema multiforme, fixed drug eruption, Stevens–Johnson syndrome, toxic epidermal necrolysis. ^kAlso known as delayed reactions.