From the Guidelines

Idiosyncratic reactions are uncommon, unpredictable, and unrelated to a drug's pharmacological action.

They are a type of Type B adverse reaction, which is non-dose related and unpredictable, as defined by the EMA and FDA 1
Idiosyncratic reactions are unrelated to the drug's pharmacological activity and usually resolve when treatment is terminated 1
They can be divided into true allergic responses (immune-mediated) and non-allergic (non-immune) sensitivities 1

The European Network for Drug Allergy categorizes hypersensitivity reactions into immediate (onset within 1-6 hours) and non-immediate (onset after 1 hour) reactions 1
Idiosyncratic reactions can be considered a type of non-immune-mediated reaction, which includes pseudo-allergic reactions, such as anaphylactoid reactions and cytokine-release syndrome (CRS) 1

Idiosyncratic reactions are unpredictable and can occur at any time, making them challenging to diagnose and manage 1
A thorough understanding of the classification and characteristics of hypersensitivity reactions is essential for accurate diagnosis and treatment 1

From the Research

Idiosyncratic drug reactions are adverse effects that cannot be explained by the known mechanisms of action of the offending agent, do not occur at any dose in most patients, and develop mostly unpredictably in susceptible individuals only 2.
These reactions are generally thought to account for up to 10% of all adverse drug reactions, but their frequency may be higher depending on the definition adopted 2.
Idiosyncratic reactions can be defined as adverse drug effects caused by genetically determined enzymatic abnormalities, but this definition is too limited and other rare and unusual adverse reactions are also considered 3.

Idiosyncratic reactions can be differentiated into:
- Immune-mediated hypersensitivity reactions, which may range from benign skin rashes to serious conditions such as drug-related rash with eosinophilia and systemic symptoms 2.
- Reactions involving unusual nonimmune-mediated individual susceptibility, often related to abnormal production or defective detoxification of reactive cytotoxic metabolites 2, 4.
- Off-target pharmacology, whereby a drug interacts directly with a system other than that for which it is intended 2.

Idiosyncratic adverse drug reactions encompass a diverse group of toxicities that can vary by drug and patient 5.
Common clinical characteristics, the identification of human leukocyte antigen risk alleles, and drug-induced proliferation of lymphocytes isolated from patients support a role for the adaptive immune system in the pathogenesis of idiosyncratic reactions 5.
Significant evidence also suggests a requirement for direct, drug-induced stress, neoantigen formation, and stimulation of an innate response, which can be influenced by properties intrinsic to both the drug and the patient 5.
Idiosyncratic reactions can affect many different organ systems, either as an isolated event or as part of a syndrome 4.

Management of patients who develop idiosyncratic reactions includes discontinuation of the implicated drug, initiation of corticosteroids (when appropriate), and symptomatic relief as required 4.
Internal organ involvement, which may initially be asymptomatic, should be monitored 4.
Knowledge of risk factors, avoidance of specific drugs in subpopulations at risk, cautious dose titration, and careful monitoring of clinical response can help minimize serious consequences of idiosyncratic reactions 2.
Pharmacogenetics can help identify genetic predisposing factors for idiosyncratic adverse drug reactions, which can inform treatment choices and prevent adverse reactions 6.