Contraindications identify circumstances under which use of a therapeutic intervention poses unacceptable risks that outweigh potential benefits, serving as critical safety information that guides both clinical trial eligibility and clinical practice decisions. In drug development, contraindications emerge from preclinical studies, clinical trial experience, and post-marketing surveillance, evolving as the evidence base grows. They represent absolute or relative prohibitions that must be clearly communicated to prescribers and patients.

Absolute contraindications describe situations where the intervention should never be used because the risk of harm is prohibitively high. These typically reflect known severe reactions, such as anaphylaxis to the drug or a component, or documented serious outcomes in specific populations, such as teratogenic effects precluding use during pregnancy. Relative contraindications indicate situations where increased risk exists but where the intervention may be used with appropriate precautions, enhanced monitoring, or when benefits clearly justify the risks.

In clinical trials, contraindications inform the exclusion criteria that determine participant eligibility. Investigators must verify the absence of contraindicated conditions during screening and remain vigilant for the development of contraindicated conditions during the trial. If a participant develops a contraindicated condition while enrolled, protocol discontinuation provisions typically require withdrawal from the investigational product. The comprehensive identification and characterization of contraindications during development is essential for informing product labeling that will guide safe use after marketing approval.