Know what questions to ask to assess drug interaction

10 questions to assess situation

Researchers at the University of Washington have developed a 10-question format as part of a Drug Interaction Probability Scale (DIPS) to provide a guide to evaluating drug interaction causation in specific patients. (See Drug Utilization Review, May 2007, p. 39) DIPS is intended to be used to assist practitioners in assessing drug interaction-induced adverse outcomes.

DIPS was designed to assess the probability of a causal relationship between a potential drug interaction and an observed event. The existing Naranjo scale provided the basis of DIPS, but was modified to reflect the important differences between a single drug event and one caused by a drug-drug interaction.

DIPS adds or subtracts points based on answers to a series of questions specific to the assessment of a potential drug interaction. John Horn, PharmD and colleagues at University of Washington said application of DIPS to a potential drug interaction requires knowledge of the pharmacologic, pharmacokinetic, and pharmacodynamic properties of both the object drug and the precipitant drug involved in the interaction.1 Proper estimation of causation, they said, may require consideration of many drug variables and properties, including factors affecting absorption, routes of elimination, pathways of metabolism, active transporters, metabolism and transporter inhibition or induction potential, activity of metabolites, standard pharmacokinetic parameters, concentration-response relationships, therapeutic response and adverse event indicators, and the contribution of disease or genetics to altered drug parameters.

Thus, they said, proper use of DIPS often requires careful and comprehensive investigation into the properties of the object and precipitant drugs.

Affirmative responses to DIPS' questions generally add to the probability that the observed event was caused by an interaction. Negative responses generally reduce the probability, while questions that cannot be answered due to lack of information or applicability are not considered in the evaluation.

Questions in the DIPS scale include:

  1. Are there previous credible reports of this interaction in humans?
  2. Is the observed interaction consistent with the known interactive properties of the precipitant drug?
  3. Is the observed interaction consistent with the known interactive properties of the object drug?
  4. Is the event consistent with the known or reasonable time course of the interaction?
  5. Did the interaction remit upon dechallenge of the precipitant drug with no change in the object drug?
  6. Did the interaction reappear when the precipitant drug was readministered in the presence of continued use of the object drug?
  7. Are there reasonable alternative causes for the event?
  8. Was the object drug detected in the blood or other fluids in concentrations consistent with the proposed interaction?
  9. Was the drug interaction confirmed by any objective evidence consistent with the effects on the object drug (other than drug concentrations from Question 8)?
  10. Was the interaction greater when the precipitant drug dose was increased or less when the precipitant drug dose was decreased?


  1. Horn JR, Hansen PD, Chan LN. Proposal for a New Tool to Evaluate Drug Interaction Cases. Annals of Pharmacotherapy. 2007; 41:674-680.