SafetyGlossary Term
A pharmacological phenomenon that occurs when the effect of one drug is altered by the presence of another drug, potentially leading to enhanced or diminished therapeutic effects or increased toxicity.
Drug-drug interactions represent a significant consideration in clinical research and medical practice, as concomitant medication use is common and can substantially affect the safety and efficacy of investigational products. These interactions may be pharmacokinetic, affecting how drugs are absorbed, distributed, metabolized, or excreted, or pharmacodynamic, affecting the physiological response to drugs through additive, synergistic, or antagonistic effects at target receptors or systems. Understanding potential interactions is essential for appropriate product labeling and safe clinical use.
Pharmacokinetic interactions frequently involve the cytochrome P450 enzyme system, which metabolizes many drugs in the liver. An investigational product that inhibits a CYP enzyme may increase blood levels of co-administered drugs metabolized by that enzyme, potentially causing toxicity. Conversely, enzyme induction may decrease blood levels of co-administered drugs, potentially reducing efficacy. Other pharmacokinetic interactions involve competition for plasma protein binding, alterations in gastrointestinal absorption, or effects on renal excretion through interactions with drug transporters.
Clinical trial protocols typically specify prohibited medications and establish monitoring requirements for interactions with commonly used concomitant medications. Exclusion criteria may preclude participants taking drugs known to interact significantly with the investigational product, while the protocol or Investigator's Brochure should guide investigators on managing participants who require interacting medications. Dedicated drug-drug interaction studies are often required by regulatory authorities to characterize interaction potential and inform prescribing recommendations that will appear in product labeling.
Protocol exclusion
"The protocol excluded participants taking strong CYP3A4 inhibitors because preclinical data indicated that co-administration could increase exposure to the investigational product by more than five-fold, substantially increasing the risk of dose-dependent adverse effects."
Interaction study
"The Phase I drug-drug interaction study demonstrated that co-administration with ketoconazole increased the AUC of the investigational product by 280%, supporting the need for dose adjustment recommendations when co-administration is unavoidable."
A response to a medicinal product that is noxious and unintended, where a causal relationship between the product and the adverse event is at least a reasonable possibility.
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product.
The strictest warning required by the FDA to appear on prescription drug labeling, alerting prescribers and patients to serious risks that may lead to death or severe injury.
The systematic evaluation of the likelihood that an adverse event was caused by the investigational product or another factor, using established criteria to determine the relationship between exposure and outcome.
A standardized one-page format developed by the Council for International Organizations of Medical Sciences for reporting suspected adverse drug reactions from clinical trials to regulatory authorities.
A pharmacological phenomenon that occurs when the effect of one drug is altered by the presence of another drug, potentially leading to enhanced or diminished therapeutic effects or increased toxicity.
Drug-drug interactions represent a significant consideration in clinical research and medical practice, as concomitant medication use is common and can substantially affect the safety and efficacy of investigational products. These interactions may be pharmacokinetic, affecting how drugs are absorbed, distributed, metabolized, or excreted, or pharmacodynamic, affecting the physiological response to drugs through additive, synergistic, or antagonistic effects at target receptors or systems. Understanding potential interactions is essential for appropriate product labeling and safe clinical use.
Pharmacokinetic interactions frequently involve the cytochrome P450 enzyme system, which metabolizes many drugs in the liver. An investigational product that inhibits a CYP enzyme may increase blood levels of co-administered drugs metabolized by that enzyme, potentially causing toxicity. Conversely, enzyme induction may decrease blood levels of co-administered drugs, potentially reducing efficacy. Other pharmacokinetic interactions involve competition for plasma protein binding, alterations in gastrointestinal absorption, or effects on renal excretion through interactions with drug transporters.
Clinical trial protocols typically specify prohibited medications and establish monitoring requirements for interactions with commonly used concomitant medications. Exclusion criteria may preclude participants taking drugs known to interact significantly with the investigational product, while the protocol or Investigator's Brochure should guide investigators on managing participants who require interacting medications. Dedicated drug-drug interaction studies are often required by regulatory authorities to characterize interaction potential and inform prescribing recommendations that will appear in product labeling.
Protocol exclusion
"The protocol excluded participants taking strong CYP3A4 inhibitors because preclinical data indicated that co-administration could increase exposure to the investigational product by more than five-fold, substantially increasing the risk of dose-dependent adverse effects."
Interaction study
"The Phase I drug-drug interaction study demonstrated that co-administration with ketoconazole increased the AUC of the investigational product by 280%, supporting the need for dose adjustment recommendations when co-administration is unavoidable."
A response to a medicinal product that is noxious and unintended, where a causal relationship between the product and the adverse event is at least a reasonable possibility.
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product.
The strictest warning required by the FDA to appear on prescription drug labeling, alerting prescribers and patients to serious risks that may lead to death or severe injury.
The systematic evaluation of the likelihood that an adverse event was caused by the investigational product or another factor, using established criteria to determine the relationship between exposure and outcome.
A standardized one-page format developed by the Council for International Organizations of Medical Sciences for reporting suspected adverse drug reactions from clinical trials to regulatory authorities.