Journal of Thrombosis and Thrombolysis

, Volume 7, Issue 2, pp 137–143 | Cite as

Management of Narrow Therapeutic Index Drugs

  • Maureen Burns


Summary. Narrow therapeutic index (NTI) drugs are agents for which small changes in systemic concentration can lead to significant changes in pharmacodynamic response. This may result in potentially subtherapeutic or toxic effects, particularly in patients with advanced age, comorbid illness, or those receiving multiple medications. Bioequivalence among generic and innovator drug products does not always ensure therapeutic equivalence, especially with regard to NTI drugs. Warfarin is a NTI drug for which substitution is now available and may occur routinely without the knowledge of the patient or practitioner. To avoid overanticoagulation or underanticoagulation, the additional cost of patient education and monitoring may actually exceed cost savings by using the less expensive generic drug product. When brand name drug is preferred by the practitioner, “no substition” must be specified on the prescription to avoid mandated generic interchange of warfarin and other NTI drugs.


Warfarin Toxic Effect Cost Saving Additional Cost Patient Education 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Benet LZ, Goyan JE. Bioeguivalence and narrow therapeutic index drugs. Pharmacotherapy 1995;15:433–440.PubMedGoogle Scholar
  2. 2.
    Wittkowsky AK. Generic warfarin: Implications for patient care. Pharmacotherapy 1997;17:640–643.PubMedGoogle Scholar
  3. 3.
    Rheinstein PH. The generic drug approval process. Am Family Physic 1993;48:1357–1360.Google Scholar
  4. 4.
    Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Assessment: Generic substitution for antiepileptic medication. Neurology 1990;40:1641–1643.Google Scholar
  5. 5.
    Nuwer MR, Browne TR, Dodson WE, et al. Generic substitution for antiepileptic drugs. Neurology 1990;40:1647–1651.PubMedGoogle Scholar
  6. 6.
    McKenzie LE, Kimberlin, CL, Pendergrast JF, Berado, DH. Potential drug interventions in a high risk ambulatory elderly population. J Geriat Drug Ther 1994;8137:49–63.Google Scholar
  7. 7.
    Pivdiro AS. Managingmedication in the elderly. Hosp Direct 1995;59–64.Google Scholar
  8. 8.
    Meredith PA. Generic drugs: Therapeutic equivalence. Drug Safety 1996;15:233–242.PubMedGoogle Scholar
  9. 9.
    Nation RL, Sanson LN. Bioeguivalence requirements for generic products. Pharmac Ther 1994;62:41–55.Google Scholar
  10. 10.
    Chen ML. Individual bioequivalence–a regulatory update. J Biopharm Stati 1997;7:5—11.Google Scholar
  11. 11.
    Bohohan BF. Generic substitution and narrow therapeutic index drugs—A national survey of retail, hospital, managed care, and nursing home pharmacists. The Pharmaceutical and Marketing Management Research Program, Research Institute of Pharmaceutical Sciences, University of Mississippi School of Pharmacy, October, 1994.Google Scholar
  12. 12.
    Calvert RT. Bioquivalence and generic prescribing: A pharmacy view. J Pharm Pharmacol 1996;48:9–10.PubMedGoogle Scholar
  13. 13.
    Pidgen A. Bioquivalence and generic prescribing: An industrial view. J Pharm Pharmacol 1996;48:11–16.PubMedGoogle Scholar
  14. 14.
    Richton-Hewitt S, Foster E, Apstein CS. Medical and economic consequences of a blinded oral anticoagulant brand change at a municipal hospital. Arch Intern Med 1988;1448:806–808.Google Scholar
  15. 15.
    Hirsh J, Dalen JE, Deykin K. Poller L, Bussey H. Oral anticoagulants: Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 1995;108(Suppl. 4):231–246.Google Scholar
  16. 16.
    Hull R, Hirsh J, Jay R, et al. Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis. N Eng J Med 1982;307:1676–1681.Google Scholar
  17. 17.
    Hylek EM, Singer D. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994;120:897–902.PubMedGoogle Scholar
  18. 18.
    Hylek EM, Skates S, Sheehan MA, Singer DE. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Eng J Med 1996;335:540–546.Google Scholar
  19. 19.
    Patnaik U, Lesdo LJ, Chan K, Williams RL. Bioequivalence of generic drugs: An American point of view. Eur J Drug Metab Pharmacokin 1996;21:159–164.Google Scholar
  20. 20.
    Todd JS. Substitution of NTI drugs: Physicians must maintain control. J Med Assoc Georgia 1997;86:121–123.Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Maureen Burns
    • 1
  1. 1.Division of Cardiovascular Medicine, Department of MedicineUniversity of Massachusetts Medical CenterWorcester

Personalised recommendations