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Table 1 Examples of different types of medicines and adverse reactions that may, in rechallenge experiments, need different strategies

From: Intentional Rechallenge and the Clinical Management of Drug-Related Problems

Small molecule drugs
Biopharmaceuticals and blood products
Antiretroviral drugs
Oncolytics and immunosuppressants
Contrast dyes, diagnostics, radiopharmaceuticals
Vaccines (revaccination); desensitization vaccines
Adverse reactions [1]
‘Type A’: These are predominantly pharmacological effects. For such reactions, a rechallenge test is designed based on pharmacological criteria and involves (low) dose within therapeutic range (or high dose in case of a therapeutic failure). Drug interactions are a subtype of Type A adverse reactions. A careful rechallenge is not necessarily dangerous
‘Type B’: These are hypersensitivity reactions. For such reactions, a rechallenge test is designed based on immunological (or metabolic) criteria and with a (very) low dose only. Often the underlying mechanism is uncertain (‘idiosyncratic’). Rechallenge is potentially dangerous. Cross hypersensitivity between drugs may occur
‘Type C’: These reactions often have no suggestive time course and may follow neither pharmacological nor immunological principles. For example, increased risk of acquiring a ‘natural’ disease (e.g. myocardial infarction, pulmonary embolism), or increased frequency of a recurrent but transient event (e.g. more frequent migraine or convulsions). A rechallenge may be inconclusive or not practicable