Idiosyncratic Reaction
An unpredictable adverse reaction to a drug that occurs in a small subset of patients, unrelated to the drug's known pharmacological effects or dose. Idiosyncratic reactions are thought to involve individual genetic or immunological factors and are difficult to predict from preclinical or clinical trial data.
Technical Context
Idiosyncratic reactions are by definition unpredictable from standard pharmacological or toxicological testing. Proposed mechanisms include: genetic polymorphisms affecting drug metabolism or immune response (pharmacogenomic susceptibility), hapten formation (drug or metabolite covalently binds to endogenous proteins, creating neo-antigens recognised by the immune system), danger hypothesis (drug causes cellular stress that provides co-stimulatory signals for immune activation), and mitochondrial dysfunction (drug impairs mitochondrial function in genetically susceptible individuals). For peptide drugs, idiosyncratic reactions are less common than for small molecules (which have more complex hepatic metabolism producing reactive intermediates). However, immune-mediated idiosyncratic reactions to biologic peptides can occur through anti-drug antibody formation with immune complex deposition or through direct T-cell-mediated responses.