Generic Versions of Narrow Therapeutic Index Drugs: A National Survey of Pharmacists' Substitution Beliefs and Practices

Clin Pharmacol Ther. 2018 Jun;103(6):1093-1099. doi: 10.1002/cpt.884. Epub 2017 Nov 22.


Small changes in bioavailability of narrow therapeutic index (NTI) drugs can alter clinical outcomes, raising concern over generic NTI substitution. We surveyed pharmacists to identify their perceptions of generic NTI drugs, their frequency of performing generic NTI substitution, and predictors of this behavior. Of 710 respondents (33% response rate), 87% perceived generic NTI drugs as effective as their brand-name versions and 94% as safe. Whereas 82% almost always performed generic NTI substitution for initial prescriptions, only 60% did for refills. Pharmacists in non-chain settings (odds ratio (OR) = 2.37; 95% confidence interval (CI) = 1.40-4.02), in practice longer (per year OR = 1.04; 95% CI = 1.02-1.06), in states with affirmative patient consent laws (OR = 1.88; 95% CI = 1.06-3.32), and in states with NTI-specific substitution requirements (OR = 1.95; 95% CI = 1.16-3.26) were more likely not to substitute initial prescriptions. Education of non-chain and veteran pharmacists and elimination of affirmative patient consent and NTI-specific substitution requirements could increase generic NTI substitution.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Attitude of Health Personnel*
  • Cross-Sectional Studies
  • Drug Substitution / psychology*
  • Drugs, Generic / administration & dosage
  • Drugs, Generic / adverse effects
  • Drugs, Generic / therapeutic use*
  • Female
  • Health Knowledge, Attitudes, Practice
  • Humans
  • Male
  • Middle Aged
  • Perception
  • Pharmacists / psychology*
  • Therapeutic Index*


  • Drugs, Generic