Introduction to Drug Interactions

  • Keith Gallicano
  • George Drusano
Part of the Infectious Disease book series (ID)


Human immunodeficiency virus (HIV), more than any other disease, is responsible for the renewed interest in drug interactions by physicians, pharmacists, nurses, scientists, and regulatory agencies. The importance of managing drug interactions in infectious diseases moved to the forefront as more drugs spanning the different classes of infectious disease agents became available to treat HIV and prevent or treat opportunistic infections and HIV-related malignancies. This has led to recognition of the potential for and impact of drug interactions in other infectious diseases and with a variety of anti-infective drug classes. Recent reviews (1, 2, 3, 4), including those in this volume, and the development of computerized drug interaction databases (5) further attest to the revived interest and importance of drug interactions in the different therapeutic areas of infectious diseases.


Human Immunodeficiency Virus Drug Interaction Study Displacement Interaction Human Immunodeficiency Virus Protease Inhibitor Drug Interac 
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.


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  1. 1.
    Piscitelli SC, Gallicano KD. Interactions among drugs for HIV and opportunistic infections. N Engl J Med 2001;344:984–996.PubMedCrossRefGoogle Scholar
  2. 2.
    Albengres E, Le Louet H, Tillement JP. Systemic antifungal agents: drug interactions of clinical significance. Drug Safety 1998;18:83–97.PubMedCrossRefGoogle Scholar
  3. 3.
    Von Rosenstiel N-A, Adam D. Macrolide antibiotics: drug interactions of clinical significance. Drug Safety 1995;13:105–122.Google Scholar
  4. 4.
    Malaty LI, Kuper JJ. Drug interactions of HIV protease inhibitors. Drug Safety 1999;20:147–169.PubMedCrossRefGoogle Scholar
  5. 5.
    Foisy MM, Tseng A. Development of an interactive computer-assisted program to manage medication therapy in HIV-infected patients. Drug Inf J 1998;32:649–656.Google Scholar
  6. 6.
    Therapeutic Products Programme Guidance Document. Drug-drug interactions: studies in vitro and in vivo (September 21, 2000). Therapeutics Products Directorate, Health Canada.Google Scholar
  7. 7.
    Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for Industry in vivo drug metabolism/drug interaction studies—study design, data analysis, and recommendations for dosing and labeling (November 1999). US Department of Health and Human Services, Food and Drug Administration.Google Scholar
  8. 8.
    Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for Industry drug metabolism/drug interaction studies in the development process: studies in vitro (April 1997). US Department of Health and Human Services, Food and Drug Administration.Google Scholar
  9. 9.
    Committee for Proprietary Medicinal Products (CPMP). Note for Guidance on the investigation of drug interactions (December 1997). The European Agency for the Evaluation of Medicinal Products Human Medicines Evaluation Unit.Google Scholar
  10. 10.
    Hepler CD, Strand LM. Opportunities and responsibilities in pharmaceutical care. Am J Hosp Pharm 1990;47:533–543.PubMedGoogle Scholar
  11. 11.
    Gauthier I, Malone M. Drug-food interactions in hospitalized patients. Drug Safety 1998;18:383–393.PubMedCrossRefGoogle Scholar
  12. 12.
    Fuhr U. Drug interactions with grapefruit juice: extent, probable mechanism and clinical relevance. Drug Safety 1998;18:251–272.PubMedCrossRefGoogle Scholar
  13. 13.
    D’Arcy PF. Adverse reactions and interactions with herbal medicines. Adverse Drug React Toxicol Rev 1991;10:189–208.PubMedGoogle Scholar
  14. 14.
    D’Arcy PF. Adverse reactions and interactions. Part 2. Adverse Drug React Toxicol Rev 1993;12:147–162.PubMedGoogle Scholar
  15. 15.
    Sahai J, Gallicano K, Oliveras L, Khaliq S, Hawley-Foss N, Garber, G. Cations in didanosine tablet reduce ciprofloxacin bioavailability. Clin Pharmacol Ther 1993;53:292–297.PubMedCrossRefGoogle Scholar
  16. 16.
    Schein JR. Cigarette smoking and clinically significant drug interactions. Ann Pharmacother 1995;29:1139–1148.PubMedGoogle Scholar
  17. 17.
    Hansten P. Drug interactions. In: Applied Therapeutics: The Clinical Use of Drugs. Vancouver, WA: Applied Therapeutics, 1995, pp. 2–10.Google Scholar
  18. 18.
    Gibaldi M. Drug interactions: part II. Ann Pharmacother 1992;26:829–834.PubMedGoogle Scholar
  19. 19.
    Tozer TN, Bois FY, Hauck WW, Chen M-L, Williams RL. Absorption rate vs exposure: which is more useful for bioequivalence testing? Pharm Res 1996;13:453–456.PubMedCrossRefGoogle Scholar
  20. 20.
    Rolan PE. Plasma protein binding displacement interactions—why are they still regarded as clinically important? Br J Clin Pharmacol 1994;37:125–128.PubMedGoogle Scholar
  21. 21.
    MacKichan JJ. Protein binding drug displacement interactions fact or fiction? Clin Pharmacokinet 1989;16:65–73.PubMedGoogle Scholar
  22. 22.
    Benet LZ, Hoener B-A. Changes in plasma protein binding have little clinical relevance. Clin Pharmacol Ther 2002;71:115–121.PubMedCrossRefGoogle Scholar
  23. 23.
    Halifax KL, Lindup WE, Barry MG, Wiltshire HR, Back DJ. Binding of the HIV protease inhibitor saquinavir to human plasma proteins. Br J Clin Pharmacol 1998;46:291P.Google Scholar
  24. 24.
    Michalets EL. Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 1998;18:84–112.PubMedGoogle Scholar
  25. 25.
    Greco WR, Bravo G, Parsons JC. The search for synergy: a critical review from a response surface perspective. Pharmacol Rev 1995;47:331–385.PubMedGoogle Scholar
  26. 26.
    Murillo J, Standiford HC, Holley HP, Tatem BA, Caplan ES. Prophylaxis against enterococcal endocarditis: comparison of the aminoglycoside component of parenteral antimicrobial regimens. Antimicrob Agents Chemother 1980;18:448–453.PubMedGoogle Scholar
  27. 27.
    Jankel CA, Speedie SM. Detecting drug interactions: a review of the literature. DICP, Ann Pharmacother 1990;24:982–988.Google Scholar
  28. 28.
    Gosney M, Tallis R. Prescription of contraindicated and interacting drugs in elderly patients admitted to hospital. Lancet 1984;1:564–567.CrossRefGoogle Scholar
  29. 29.
    Shinn AF, Shrewsbury RP, Anderson KW. Development of a computerized drug interaction database (MEDICOM) for use in a patient specific environment. Drug Inf J 1983;17:205–210.PubMedGoogle Scholar
  30. 30.
    Jinks MJ, Hansten PD, Hirschman JL. Drug interaction exposures in an ambulatory Medicaid population. Am J Hosp Pharm 1979;36:923–927.PubMedGoogle Scholar
  31. 31.
    Mitchell GW, Stanaszek WF, Nichols NB. Documenting drug-drug Interactions in ambulatory patients. Am J Hosp Pharm 1979;36:653–657.PubMedGoogle Scholar
  32. 32.
    Cooper JW, Wellins I, Fish KH, Loomis ME. Frequency of potential drug-drug interactions. J Am Pharm Assoc 1975;15:24–31.PubMedGoogle Scholar
  33. 33.
    Durrence CW III, DiPiro JT, May JR, Nesbit RR, Sisley JF, Cooper JW. Potential drug interactions in surgical patients. Am J Hosp Pharm 1985;42:1553–1556.PubMedGoogle Scholar
  34. 34.
    Puckett WH, Visconti JA. An epidemiologic study of the clinical significance of drug-drug interactions in a private community hospital. Am J Hosp Pharm 1971;28:247–253.PubMedGoogle Scholar
  35. 35.
    Foisy MM, Gough K, Quan CM, Harris K, Ibanez D, Phillips A. Hospitalizations due to adverse drug reactions and interactions pre-and post-HAART [abstract B215]. Can J Infect Dis 1999;10(suppl B):24B.Google Scholar
  36. 36.
    Jankel CA, Fitterman LK. Epidemiology of drug-drug interactions as a cause of hospital admissions. Drug Safety 1993;9:51–59.PubMedGoogle Scholar
  37. 37.
    Honig PK, Wortham DC, Amani K, Conner D, Mullin JC, Cantilena LR. Terfenadine-ketoconazole interaction: pharmacokinetic and electrocardiographic consequences. JAMA 1993;269:1513–1518.PubMedCrossRefGoogle Scholar
  38. 38.
    Henry JA, Hill IR. Fatal interaction between ritonavir and MDMA. Lancet 1998;352:1751–1752.PubMedCrossRefGoogle Scholar
  39. 39.
    Lees RS, Lees AM. Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole. N Engl J Med 1995;333:664–665.PubMedCrossRefGoogle Scholar
  40. 40.
    Pollak PT, Sketris IS, MacKenzie SL, Hewlett TJ. Delirium probably induced by clarithromycin in a patient receiving fluoxetine. Ann Pharmacother 1995;29:486–488.PubMedGoogle Scholar
  41. 41.
    Kwan TC, Wahba WW, Wildeman RA. Drug interactions: a retrospective study of its epidemiology, clinical significance and influence upon hospitalization. Can J Hosp Pharm 1979;32:12–16.PubMedGoogle Scholar
  42. 42.
    Hamilton RA, Briceland LL, Andritz MH. Frequency of hospitalization after exposure to known drug-drug interactions in a Medicaid population. Pharmacother 1998;18:1112–1120.Google Scholar
  43. 43.
    Kennedy DT, Hayney MS, Lake KD. Azathioprine and allopurinol: the price of an avoidable drug interaction. Ann Pharmacother 1996;30:951–954.PubMedGoogle Scholar
  44. 44.
    Nightingale CH, Quintiliani R. Cost of oral antibiotic therapy. Pharmacother 1997;17:302–307.Google Scholar
  45. 45.
    Roberts JS, Watrous ML, Schulz RM, Mauch RP, Nightengale BS. Quantifying the clinical significance of drug-drug interactions: scaling pharmacists’ perceptions of a common interaction classification scheme. Ann Pharmacother 1996;30:926–934.PubMedGoogle Scholar
  46. 46.
    Steinijans VW, Hartmanns M, Huber R, Radtke HW. Lack of pharmacokinetic interaction as an equivalence problem. Int J Clin Pharmacol Ther Toxicol 1991;29:323–328.PubMedGoogle Scholar
  47. 47.
    Nix DE, Watson WA, Lener ME, et al. Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin. Clin Pharmacol Ther 1989;46:700–705.PubMedCrossRefGoogle Scholar
  48. 48.
    Rybak MJ Albrecht LM, Boike SC, Chandrasekar PH. Nephrotoxicity of vancomycin, alone and with an aminoglycoside. J Antimicrob Chemother 1990;25:679–687.PubMedCrossRefGoogle Scholar
  49. 49.
    Honig PK, Woosley RL, Zamani K, Conner DP, Cantilena LR Jr. Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin. Clin Pharmacol Ther 1992;52:231–238.PubMedCrossRefGoogle Scholar
  50. 50.
    Tatro DS, ed. Drug interaction facts. Facts and comparisons. St. Louis, MO: Wolters Kluwer, 1998.Google Scholar
  51. 51.
    Rapp RP. Pharmacokinetics and pharmacodynamics of intravenous and oral azithromycin: enhanced tissue activity and minimal drug interactions. Ann Pharmacother 1998;32:785–793.PubMedCrossRefGoogle Scholar
  52. 52.
    Hansten PD, Horn JR, eds. Hansten and Horn’s Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics, 1999.Google Scholar
  53. 53.
    Von Moltke LL, Greenblatt DJ, Schmider J, Wright CE, Harmatz JS, Shader RI. In vitro approaches to predicting drug interactions in vivo. Biochem Pharmacol 1998;55:113–122.CrossRefGoogle Scholar
  54. 54.
    Touw DJ. Clinical implications of genetic polymorphisms and drug interactions mediated by cytochrome P450 enzymes. Drug Metab Drug Interact 1997;14:55–82.Google Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • Keith Gallicano
    • 1
  • George Drusano
    • 2
  1. 1.BiopharmaceuticsWatson Laboratories, Inc.Corona
  2. 2.New York State Department of HealthOrdway Research InstituteAlbany

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