By: Nayon Kang, Lucy Chung, David Vallee

A reaction between two (or more) drugs or between a drug and a food or supplement. An existing medical condition can also cause a drug interaction. A drug interaction can decrease or increase the action of the drug(s) or cause adverse effects. 1

This interaction could result in a range of outcomes, from unwanted effects of clinical significance to no clinically significant impact. The potential for drug interactions increases with polypharmacy, and the management should involve efforts from both healthcare providers, as well as patients. 2

Different Types of Drug Interactions: 3

  • Drug-Drug Interaction: a reaction between two or more drugs
  • Drug-Food interaction: a reaction between a drug and a food or a beverage
    • Grapefruit and grapefruit juice is an example that may lead to an increased level of a drug that could cause unwanted harmful effects4
  • Drug-Condition interaction: a reaction that occurs when taking a drug while having a certain medication condition
    • Example: Nasal decongestant usage in patients with high blood pressure may cause an unwanted reaction

Mechanisms of Drug-Drug Interactions (DDI)5,6

The mechanisms for DDIs can be classified into those related to the pharmacokinetics or pharmacodynamics of a drug. Pharmacokinetic interaction involves mechanisms of what the body does to a drug, such as how it’s broken down or removed from the body, and pharmacodynamic interaction involves mechanisms of what a drug does to a body, such as additive or antagonistic effects. Table 1 shows some of the examples of these interactions.

Strategies For Managing DDIs5,6

Physicians, pharmacists, and other healthcare providers play an important role in assessing patient’s

Table 1. Examples of Mechanisms of Drug-Drug Interactions5,6

medications to ensure safe and appropriate uses. Additionally, patient engagement is also important for gathering accurate and comprehensive medication history to guide future medication therapies and to avoid any potential DDI risks.

Management of drug interactions should be multi-modal and below are some important considerations:

  1. Identifying potential DDI as well as identifying patients at high risk of DDI, such as those receiving multiple medications for chronic conditions, will be a crucial step.
    • There are several drug interaction databases that provide information on drug interaction risks, magnitude of interactions, and the severity of risk (Figure 1). Pharmacists, who are familiar with utilizing these databases, can be a great resource in providing comprehensive assessment of DDI risks.
  2. Sometimes a DDI is unavoidable and drug interactions will need to be closely monitored.
    • Therapeutic drug monitoring can be an important instrument in this case, especially for drugs that are routinely monitored, such as warfarin, phenytoin, vancomycin, or amino-glycosides, to guide dose adjustment or alternative dosing strategy.
  3. Patient engagement and education are important for reducing DDI risks by:
    • Clearly communicating current medication regimen to identify any potential DDI risks and ‘de-prescribe’ any duplicate therapies that could introduce DDI
    • Ensuring patients understand and communicate any changes made to the current medication regimen to other healthcare providers to avoid future DDI risk.

DDIs in Clinical Trials and Challenges

Clinical trials involving investigational products (IP) that have never been approved or made available commercially can be challenging due to limited availability of clinical and non-clinical data. Also, the available data will evolve as the pharmaceutical companies continue to undergo different testing to fulfill requirements for the new drug approval processes, but the information may be limited to the research team only. Moreover, in blinded, placebo-controlled trials, some of the DDI management strategies, such as utilizing therapeutic drug monitoring to assess drug levels and guide dose adjustments, may not be feasible to maintain blinding and to avoid sub-therapeutic dosing in participants who may be receiving blind-ed placebo treatment. When IP is a victim drug in a DDI, the observed outcomes may not reflect the true efficacy of the study product and therefore impact the overall study results. Above mentioned strategies, as well as trial-specific resources may need to be developed to avoid DDI risks and ensure patient safety and robust results on drug efficacy.


DCR pharmacy team is happy to hear your thoughts! Please feel free to share your experiences. We can be reached via email at DCRPharmacy@mail.nih.gov

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