Advertisement

Antifungal Agents

  • Paul O. Gubbins
  • Scott A. McConnell
  • Scott R. Penzak
Part of the Infectious Disease book series (ID)

Abstract

During the past several decades, fungi have become increasingly common pathogens, particularly among critically ill or immunosuppressed patients. Unfortunately, advances in antifungal therapy have not kept pace with this trend. Historically, antifungal development has lagged significantly behind that of antibacterial therapy. For many years there have been few choices to select from for the treatment of systemic mycoses. Though few in number, systemically acting antifungal agents can cause pharmacokinetic or pharmacodynamic drug—drug interactions by a variety of mechanisms. Therefore, they have the potential to interact with a vast array of medicines. Given the patient populations in whom systemic mycoses typically occur, the increased use of antifungal therapy, and the limited selection of antifungal agents, clinicians must understand the drug interaction profile of this small but increasingly important class of drugs.

Keywords

Antifungal Agent Cryptococcal Meningitis CYP3A4 Substrate Systemic Mycosis Oral Availability 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Gallis HA, Drew RH, Pickard WW. Amphotericin B: 30 years of clinical experience. Rev Infect Dis 1990; 12: 308–329.PubMedCrossRefGoogle Scholar
  2. 2.
    Yamaguchi H, Abe S, Tokuda Y. Immunomodulating activity of antifungal drugs. Ann NY Acad Sci 1993; 685: 447–457.PubMedCrossRefGoogle Scholar
  3. 3.
    Wong-Berringer A, Jacobs RA, Guglielmo BJ. Lipid formulations of amphotericin B: clinical efficacy and toxicities. Clin Infect Dis 1998; 27: 603–618.CrossRefGoogle Scholar
  4. 4.
    Daneshmend TK, Warnock DW. Clinical pharmacokinetics of systemic antifungal drugs. Clin Pharmacokinet 1983; 8: 17–42.PubMedCrossRefGoogle Scholar
  5. 5.
    Como JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. N Engl J Med 1994; 330: 263–272.PubMedCrossRefGoogle Scholar
  6. 6.
    Wacher VJ, Wu CJ, Benet LZ. Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy. Mol Carcinogen 1995; 13: 129–134.CrossRefGoogle Scholar
  7. 7.
    Wacher VJ, Silverman JA, Zhang Y, Benet LZ. Role of P-glycoprotein and cytochrome P450 in limiting oral absorption of peptides and peptidomimetics. J Pharm Sci 1998; 87: 1322–1330.PubMedCrossRefGoogle Scholar
  8. 8.
    Heykants J, Van Peer A, Van de Velde V, et al. The clinical pharmacokinetics of itraconazole: an overview. Mycoses 1989; 32 (suppl 1): 67–87.PubMedGoogle Scholar
  9. 9.
    Van de Velde VJS, Van Peer A, Heykants JJP, et al. Effect of food on the pharmacokinetics of a new hydroxypropyl-(3-cyclodextrin formulation of itraconazole. Pharmacother 1996; 16: 424–428.Google Scholar
  10. 10.
    Barone JA, Moskovitz BL, Guarnieri J, et al. Enhanced bioavailability of itraconazole in hydroxypropyl-(3-cyclodextrin solution versus capsules in healthy volunteers. Antimicrob Agents Chemother 1998; 42: 1862–1865.PubMedGoogle Scholar
  11. 11.
    Debruyne D, Ryckelynk JP. Clinical Pharmacokinetics of fluconazole. Clin Pharmacokinet 1993; 24: 10–27.PubMedCrossRefGoogle Scholar
  12. 12.
    Thummel KE, Wilkinson GR. In vitro and in vivo drug interactions involving human CYP3A. Annu Rev Pharmacol Toxicol 1998; 38: 389–430.PubMedCrossRefGoogle Scholar
  13. 13.
    Albengres E, Le Louët H, Tillement JP. Systemic antifungal agents: drug interactions of clinical significance. Drug Safety 1998; 18: 83–97.PubMedCrossRefGoogle Scholar
  14. 14.
    Poirier JM, Cheymol G. Optimization of itraconazole therapy using target drug concentrations. Clin Pharmacokinet 1998; 35: 461–473.PubMedCrossRefGoogle Scholar
  15. 15.
    Brammer KW, Coakley AJ, Jezequel SG, Tarbit MH. The disposition and metabolism of [laC] fluconazole in humans. Drug Metab Disp 1991; 19: 764–767.Google Scholar
  16. 16.
    Black DJ, Kunze KL, Wienkers LC, et al. Warfarin-fluconazole II. A metabolically based drug interaction: in vivo studies. Drug Metab Disp 1996; 24: 422–428.Google Scholar
  17. 17.
    Campana C, Regazzi MB, Buggia I, Molinaro M. Clinically significant drug interactions with cyclosporin: an update. cyclosporine with antimicrobial agents. Clin Pharmacokinet 1996; 30: 141–179.PubMedCrossRefGoogle Scholar
  18. 18.
    Paterson DL, Singh N. Interactions between tacrolimus and antimicrobial agents. Clin Infect Dis 1997; 25: 1430–1440.PubMedCrossRefGoogle Scholar
  19. 19.
    Kennedy MS, Deeg HJ, Siegel M, Crowley JJ, Storb R, Thomas ED. Acute renal toxicity with combined use of amphotericin B and cyclosporine after marrow transplantation. Transplantation 1983; 35: 211–215.PubMedCrossRefGoogle Scholar
  20. 20.
    White MH, Bowden RA, Sandler ES, et al. Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia. Clin Infect Dis 1998; 27: 296–302.PubMedCrossRefGoogle Scholar
  21. 21.
    Noskin G, Pietrelli L, Gurwith M, Bowden R. Treatment of invasive fungal infections with amphotericin B colloidal dispersion in bone marrow transplant recipients. Bone Marrow Transplant 1999; 23: 697–703.PubMedCrossRefGoogle Scholar
  22. 22.
    Meheta J, Kelsey S, Chu P, et al. Amphotericin B lipid complex (ABLC) for the treatment of confirmed or presumed fungal infections in immunocomprised patients with hematologic malignancies. Bone Marrow Transplant 1997; 20: 39–43.CrossRefGoogle Scholar
  23. 23.
    Ringdén O, Andström E, Remberger M, Svahn BM, Tollemar J. Safety of liposomal amphotericin B (AmBisome) in 187 transplant recipients treated with cyclosporine. Bone Marrow Transplant 1994; 14 (suppl 5): S10 - S14.PubMedGoogle Scholar
  24. 24.
    Prentice HG, Hann IM, Herbrecht R, et al. A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients. Br J Haematol 1997; 98: 711–718.PubMedCrossRefGoogle Scholar
  25. 25.
    June CH, Thompson CB, Kennedy MS, Nims J, Thomas ED. Profound hypomagnesemia associated with the use of cyclosporine for marrow transplantation. Transplantation 1985; 39: 620–624.PubMedCrossRefGoogle Scholar
  26. 26.
    Churchill DN, Seely J. Nephrotoxicity associated with combined gentamicin-amphotericin B therapy. Nephron 1977; 19: 176–181.PubMedCrossRefGoogle Scholar
  27. 27.
    Stein RS, Albridge K, Lenox RK, Ray W, Flexner JM. Nephrotoxicity in leukemic patients receiving empirical amphotericin B and aminoglycosides. South Med J 1988; 81: 1095–1099.PubMedCrossRefGoogle Scholar
  28. 28.
    Stamm AM, Diaso RB, Dismukes WE, et al. Toxicity of amphotericin B plus flucytosine in 194 patients with cryptococcal meningitis. Am J Med 1987; 83: 236–242.PubMedCrossRefGoogle Scholar
  29. 29.
    Bennett JE, Dismukes WE, Duma RJ, et al. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N Engl J Med 1979; 301: 126–131.PubMedCrossRefGoogle Scholar
  30. 30.
    Block ER, Bennett JE. Pharmacological studies with 5-fluorocytosine. Antimicrob Agents Chemother 1972; 1: 476–482.PubMedCrossRefGoogle Scholar
  31. 31.
    Viviani MA. Flucytosine-what is its future? J Antimicrob Chemother 1995; 35: 241–244.PubMedCrossRefGoogle Scholar
  32. 32.
    Chung DK, Koenig MG. Reversible cardiac enlargement during treatment with amphotericin B and hydrocortisone. Am Rev Respir Dis 1971; 103: 831–841.PubMedGoogle Scholar
  33. 33.
    Fleisher D, Li C, Zhou Y, Pao LH, Karim A. Drug, meal and formulation interactions influencing drug absorption after oral administration: clinical implications. Clin Pharmacokinet 1999; 36: 233–254.PubMedCrossRefGoogle Scholar
  34. 34.
    Lange D, Pavao JH, Wu J, Klausner M. Effect of a cola beverage on the bioavailability of itraconazole in the presence of H2 blockers. J Clin Pharmacol 1997; 37: 535–540.PubMedCrossRefGoogle Scholar
  35. 35.
    Hoeschele JD, Roy AK, Pecoraro VL, Carver PL. In vitro analysis of the interaction between sucralfate and ketoconazole. Antimicrob Agents Chemother 1994; 38: 319–325.PubMedCrossRefGoogle Scholar
  36. 36.
    Omar G, Whiting PH, Hawksworth GM, Humphrey MJ, Burke MD. Ketoconazole and fluconazole inhibition of the metabolism of cyclosporin A by human liver in vitro. Ther Drug Monit 1997; 19: 436–445.PubMedCrossRefGoogle Scholar
  37. 37.
    Jalava KM, Partanen J, Neuvonen PJ. Itraconazole decreases renal clearance of digoxin. Ther Drug Monit 1997; 19: 609–613.PubMedCrossRefGoogle Scholar
  38. 38.
    Kaukonen KM, Olkkola KT, Neuvonen PJ. Itraconazole increases plasma concentrations of quinidine. Clin Pharmacol Ther 1997; 62: 510–517.PubMedCrossRefGoogle Scholar
  39. 39.
    de Lannoy IAM, Koren G, Klein J, Charuk J, Silverman M. Cyclosporin and quinidine inhibition of renal digoxin excretion: evidence for luminal secretion of digoxin. Am J Physiol 1992; 263: F613 - F622.PubMedGoogle Scholar
  40. 40.
    Baciewicz AM, Baciewicz FA. Ketoconazole and fluconazole drug interactions. Arch Intern Med 1993; 153: 1970–1976.PubMedCrossRefGoogle Scholar
  41. 41.
    Hall SD, Thummel KE, Watkins PB, et al. Molecular and physical mechanisms of first-pass extraction. Drug Metab Dispos 1999; 27: 161–166.PubMedGoogle Scholar
  42. 42.
    Gomez DY, Wacher VJ, Tomlanovich SJ, Hebert MF, Benet LZ. The effects of ketoconazole on intestinal metabolism and bioavailability of cyclosporine. Clin Pharmacol Ther 1995; 58: 15–19.PubMedCrossRefGoogle Scholar
  43. 43.
    Keogh A, Spratt P, McCosker C, MacDonald P, Mundy J, Kaan A. Ketoconazole to reduce the need for cyclosporine after cardiac surgery. N Engl J Med 1995; 333: 628–633.PubMedCrossRefGoogle Scholar
  44. 44.
    Zimmerman NT, Yeates RA, Laufen H, Pfaff G, Wildfeuer A. Influence of concomitant food intake on the oral absorption of two triazole antifungal agents, itraconazole and fluconazole. Eur J Clin Pharmacol 1994; 46: 147–150.CrossRefGoogle Scholar
  45. 45.
    Kanda Y, Kami M, Matsuyama T, et al. Plasma concentrations of itraconazole in patients receiving chemotherapy for hematological malignancies: the effect of famotidine on the absorption of itraconazole. Hematol Oncol 1998; 16: 33–37.PubMedCrossRefGoogle Scholar
  46. 46.
    Lim SG, Sawyerr AM, Hudson M, Sercombe J, Pounder RE. Short report: the absorption of fluconazole and itraconazole under conditions of low intragastric acidity. Aliment Pharmacol Ther 1993; 7: 317–321.PubMedCrossRefGoogle Scholar
  47. 47.
    Jaruratanasirikul S, Sriwiriyajan S. Effect of omeprazole on the pharmacokinetics of itraconazole. Eur J Clin Pharmacol 1998; 54: 159–161.PubMedCrossRefGoogle Scholar
  48. 48.
    May DB, Drew RH, Yedinak KC, Bartlett JA. Effect of simultaneous didanosine administration on itraconazole absorption in healthy volunteers. Pharmacother 1994; 14: 509–513.Google Scholar
  49. 49.
    Christians U, Jacobsen W, Floren LC. Metabolism and drug interactions of 3-hydroxy3-methylglutaryl coenzyme A reductase inhibitors in transplant patients: are the statins mechanistically similar? Pharmacol Ther 1998; 80: 1–34.PubMedCrossRefGoogle Scholar
  50. 50.
    Neuvonen PJ, Jalava KM. Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther 1996; 60: 54–61.PubMedCrossRefGoogle Scholar
  51. 51.
    Neuvonen PJ, Kantola T, Kivistö KT. Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther 1998; 63: 332–341.PubMedCrossRefGoogle Scholar
  52. 52.
    Kantola T, Kivistö KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics of atorvastatin. Clin Pharmacol Ther 1998; 64: 58–65.PubMedCrossRefGoogle Scholar
  53. 53.
    Kantola T, Kivistö KT, Neuvonen PJ. Effect of itraconazole on cerivastatin pharmacokinetics. Eur J Clin Pharmacol 1999; 54: 851–855.PubMedCrossRefGoogle Scholar
  54. 54.
    Miick W. Rational assessment of the interaction profile of cerivastatin supports its low propensity for drug interactions. Drugs 1998; 56 (suppl 1): 15–23.Google Scholar
  55. 55.
    Kivistö KT, Kantola T, Neuvonen PJ. Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. Br J Clin Pharmacol 1998; 46: 49–53.PubMedCrossRefGoogle Scholar
  56. 56.
    Olkkola KT, Ahonen J, Neuvonen PJ. The effect of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesth Ana1g 1996; 82: 511–516.Google Scholar
  57. 57.
    Varhe A, Olkkola KT, Neuvonen PJ. Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 1994; 56: 601–607.PubMedCrossRefGoogle Scholar
  58. 58.
    Neuvonen PJ, Varhe A, Olkkola KT. The effect of ingestion time interval on the interaction between itraconazole and triazolam. Clin Pharmacol Ther 1996; 60: 326–331.PubMedCrossRefGoogle Scholar
  59. 59.
    Backman JT, Kivistö KT, Olkkola KT, Neuvonen PJ. The area under the plasma concentration-time curve for oral midazolam is 400-fold larger during treatment with itraconazole than with rifampicin. Eur J Clin Pharmacol 1998; 54: 53–58.PubMedCrossRefGoogle Scholar
  60. 60.
    Ahonen J, Olkkola KT, Neuvonen PJ. The effect of the antimycotic itraconazole on the pharmacokinetics and pharmacodynamics of diazepam. Fundam Clin Pharmacol 1996; 10: 314–318.PubMedCrossRefGoogle Scholar
  61. 61.
    Ahonen J, Olkkola KT, Neuvonen PJ. Lack of effect of the antimycotic itraconazole on the pharmacokinetics or pharmacodynamics of temazepam. Ther Drug Monit 1996; 18: 124–127.PubMedCrossRefGoogle Scholar
  62. 62.
    Kivistö KT, Lamberg TS, Kantola T, Neuvonen PJ. Plasma buspirone concentrations are greatly increased by erythromycin and itraconazole. Clin Pharmacol Ther 1997; 62: 348–354.PubMedCrossRefGoogle Scholar
  63. 63.
    Luurila H, Kivistö KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zolpidem. Eur J Clin Pharmacol 1998; 54: 163–166.PubMedCrossRefGoogle Scholar
  64. 64.
    Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokinet 1997; 32: 210–258.PubMedCrossRefGoogle Scholar
  65. 65.
    Yasui N, Kondo T, Otani K, et al. Effects of itraconazole on the steady-state plasma concentrations of haloperidol and its reduced metabolite in schizophrenic patients: in vivo evidence of the involvement of CYP3A4 for haloperidol metabolism. J Clin Psychopharmacol 1999; 19: 149–154.PubMedCrossRefGoogle Scholar
  66. 66.
    Raaska K, Neuvonen. Serum concentrations of clozapine and N-desmethylclozapine are unaffected by the potent CYP3A4 inhibitor itraconazole. Eur J Clin Pharmacol 1998; 54 (2): 167–170.PubMedCrossRefGoogle Scholar
  67. 67.
    Kramer MR, Marshall SE, Denning DW, et al. Cyclosporine and itraconazole in heart and lung transplant recipients. Ann Intern Med 1990; 113: 327–329.PubMedCrossRefGoogle Scholar
  68. 68.
    McLachlan Ai, Tett SE. Effect of metabolic inhibitors on cyclosporine pharmacokinetics using a population approach. Ther Drug Monit 1998; 20: 390–395.PubMedCrossRefGoogle Scholar
  69. 69.
    Billaud EM, Guillemain R, Tacco F, Chevalier P. Evidence for a pharmacokinetic interaction between itraconazole and tacrolimus in organ transplant patients. Br J Clin Pharmacol 1998; 46: 271–272.PubMedGoogle Scholar
  70. 70.
    Jalava KM, Olkkola KT, Neuvonen PJ. Itraconazole greatly increases plasma concentrations and effects of felodipine. Clin Pharmacol Ther 1997; 61: 410–415.PubMedCrossRefGoogle Scholar
  71. 71.
    Varis T, Kaukonen KM, Kivistö KT, Neuvonen N. Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole. Clin Pharmacol Ther 1998; 64: 363–368.PubMedCrossRefGoogle Scholar
  72. 72.
    Lukkari E, Juhakoski A, Aranko K, Neuvonen PJ. Itraconazole moderately increases serum concentrations of oxybutynin but does not affect those of the active metabolite. Eur J Clin Pharmacol 1997; 52: 403–406.PubMedCrossRefGoogle Scholar
  73. 73.
    Lomaestro BM, Piatek MA. Update on drug interactions with azole antifungal agents. Ann Pharmacother 1998; 32: 915–928.PubMedCrossRefGoogle Scholar
  74. 74.
    Bonay M, Jonville-Bera AP, Diot P, Lemarie E, Lavandier M, Autret E. Possible interaction between phenobarbital, carbamazepine and itraconazole. Drug Safety 1993; 9: 309–311.PubMedCrossRefGoogle Scholar
  75. 75.
    Ducharme MP, Slaughter RL, Warbasse LH, et al. Itraconazole and hydroxyitraconazole serum concentrations are reduced more than tenfold by phenytoin. Clin Pharmacol Ther 1995; 58: 617–624.PubMedCrossRefGoogle Scholar
  76. 76.
    Sachs MK, Blanchard LM, Green Pi. Interaction of itraconazole and digoxin. Clin Infect Dis 1993; 16: 400–403.PubMedCrossRefGoogle Scholar
  77. 77.
    Ahonen J, Olkkola KT, Neuvonen PJ. Effect of route of administration of fluconazole on the interaction between fluconazole and midazolam. Eur J Clin Pharmacol 1997; 51: 415–419.PubMedCrossRefGoogle Scholar
  78. 78.
    Varhe A, Olkkola KT, Neuvonen PJ. Fluconazole, but not terbinafine, enhances the effects of triazolam by inhibiting its metabolism. Br J Clin Pharmacol 1996; 41: 319–323.PubMedCrossRefGoogle Scholar
  79. 79.
    Varhe A, Olkkola KT, Neuvonen PJ. Effect of fluconazole dose on the extent of fluconazole-triazolam interaction. Br J Clin Pharmacol 1996; 42: 465–470.PubMedCrossRefGoogle Scholar
  80. 80.
    Krüger HU, Schuler U, Zimmermann R, Ehninger G. Absence of significant interaction of fluconazole with cyclosporin. J Antimicrob Chemother 1989; 24: 781–786.PubMedCrossRefGoogle Scholar
  81. 81.
    Canafax DM, Graves NM, Hilligoss DM, Carleton BC, Gardner MJ, Matas AJ. Interaction between cyclosporine and fluconazole in renal allograft recipients. Transplantation 1991; 51: 1014–1018.PubMedCrossRefGoogle Scholar
  82. 82.
    Lopez-Gil JA. Fluconazole-cyclosporine interaction: a dose-dependent effect? Ann Pharmacother 1993; 27: 427–430.PubMedGoogle Scholar
  83. 83.
    Manez R, Martin M, Raman D, et al. Fluconazole therapy in transplant recipients receiving FK506. Transplantation 1994; 57: 1521–1523.PubMedGoogle Scholar
  84. 84.
    Osowski CL, Dix SP, Lin LS, Mullins RE, Gellar RB, Wingard JR. Evaluation of the drug interaction between intravenous high-dose fluconazole and cyclosporine or tacrolimus in bone marrow transplant recipients. Transplantation 1996; 61: 1268–1272.PubMedCrossRefGoogle Scholar
  85. 85.
    Blum RA, Wilton JH, Hilligoss DM, et al. Effect of fluconazole on disposition of phenytoin. Clin Pharmacol Ther 1991; 49: 420–425.PubMedCrossRefGoogle Scholar
  86. 86.
    Kaukonen KM, Olkkola KT, Neuvonen PJ. Fluconazole but not itraconazole decreases the metabolism of losartan to E-3174. Eur J Clin Pharmacol 1998; 445–449.Google Scholar
  87. 87.
    Palkama VJ, Isohanni MH, Neuvonen PJ, Olkkola KT. The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil. Anesth Analg 1998; 87: 190–194.PubMedGoogle Scholar
  88. 88.
    Apseloff G, Hilligoss DM, Gardner MJ, et al. Induction of fluconazole metabolism by rifampin: in vivo study in humans. J Clin Pharmacol 1991; 31: 358–361.PubMedCrossRefGoogle Scholar
  89. 89.
    Sahai J, Gallicano K, Pakuts A, Cameron DW. Effect of fluconazole on zidovudine pharmacokinetics in patients infected with Human Immunodeficiency Virus. J Infect Dis 1994; 169: 1103–1107.PubMedCrossRefGoogle Scholar
  90. 90.
    Schutze GE, Hickerson SL, Fortin E, et al. Blastomycosis in children, Clin Infect Dis 1996; 22: 496–502.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Paul O. Gubbins
  • Scott A. McConnell
  • Scott R. Penzak

There are no affiliations available

Personalised recommendations