, Volume 50, Issue 4, pp 658–690 | Cite as


An Update of its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Use in Major Superficial and Systemic Mycoses in Immunocompromised Patients
  • Karen L. Goa
  • Lee B. Barradell
Drug Evaluation



Fluconazole is a triazole antifungal agent which is now an established part of therapy in patients with immune deficiencies. It is effective against oropharyngeal/ oesophageal candidiasis (candidosis) when used orally once daily either as treatment or secondary prophylaxis in patients with AIDS or as treatment or primary prophylaxis in neutropenia associated with cancer therapy. Fluconazole also resolves symptoms in up to 60% of patients with cryptococcal meningitis and AIDS. However, in this infection its efficacy as treatment relative to that of amphotericin B is equivocal, and its major role is as the drug of choice for maintenance therapy following amphotericin B induction. In this regard, fluconazole has been proven superior to amphotericin B and to itraconazole 200 mg/day.

Comparisons with other drugs used for the treatment of mucosal candidiasis in patients with AIDS show fluconazole to be superior to nystatin, similar to itraconazole and at least as effective as clotrimazole and ketoconazole; it was more so than the latter azole in 1 study. In patients undergoing chemotherapy or bone marrow transplantation, fluconazole as primary prophylaxis has produced greater clinical benefit than a clotrimazole regimen.

The incidence of adverse events appears to be somewhat higher in patients with AIDS compared with HIV-negative cohorts, but the qualitative pattern of events is similar. The most frequent events are gastrointestinal complaints, headache and skin rash: rare exfoliative skin reactions and isolated instances of clinically overt hepatic dysfunction have occurred in patients with AIDS.

Issues yet to be clarified include: the use of fluconazole in children with AIDS, in whom results have been promising; its efficacy against other fungal infections encountered in immunocompromised patients; whether the drug influences mortality, as has been suggested by one placebo-controlled trial in patients undergoing bone marrow transplant; and the appropriateness of its potential for use as primary prophylaxis against cryptococcal meningitis in patients with AIDS, where it shows efficacy but there is concern over increasing risk of development of secondary resistance.

Notwithstanding these undefined aspects of its clinical profile, fluconazole is now confirmed as an important antifungal drug in the management of fungal infections in patients with immune deficiencies. In patients with AIDS it is the present drug of choice as maintenance therapy against cryptococcal meningitis and is a preferred agent for secondary prophylaxis against candidat infections; it is also a favoured agent for primary prophylaxis in patients at risk because of neutropenia associated with chemotherapy or bone marrow transplantation.

Pharmacodynamic Properties

Fluconazole is fungistatic and acts by obstructing the conversion of fungal lanosterol to ergosterol, thereby inhibiting membrane sterol synthesis and preventing fungal cell replication. Fluconazole is much more selective than ketoconazole for cytochrome P450 enzymes in fungi than in mammalian cells: most evidence argues against a detrimental effect of fluconazole on mammalian steroid hormone production.

While of unproven predictive value clinically, recently improved in vitro susceptibility testing methods for antifungal drugs indicate that fluconazole is active against several of the most common yeasts encountered in immunocompromised patients. Most Candida spp., with the notable exception of C. krusei, are susceptible, as is Cryptococcus neoformans. C. (Torulopsis) glabrata and Histoplasma capsulatum show variable susceptibility. Aspergillus spp. are resistant to fluconazole. In vivo animal models of immunocompromised hosts parallel these findings. In vitro and limited in vivo data suggest that fluconazole lacks deleterious effects on the immune system.

Secondary resistance of Candida spp. to fluconazole appears to be emerging, as evidenced both microbiologically and clinically, but is presently uncommon. It has become most apparent in patients with advanced AIDS in whom C. albicans is the most prevalent progressively resistant strain. Resistance is less well-documented in other immunocompromised patients.

Pharmacokinetic Properties

Pharmacokinetic parameters of fluconazole do not differ substantially between immunocompromised and healthy individuals and are similar for oral and intravenous formulations. Absorption of oral fluconazole formulations is almost complete in patients with AIDS without gastroenteritis. It is unaffected by the presence of hypochlorhydria provoked, for example, by AIDS or by vomiting in patients with malignancies undergoing chemotherapy.

Fluconazole is poorly bound to plasma proteins (12%) and is widely distributed to body tissues and fluids, including CSF. The volume of distribution (50 to 60L) approximates the volume of body water. In contrast to other available azoles, fluconazole is excreted primarily by renal rather than hepatic mechanisms. Its long elimination half-life (t½β) of about 35 hours permits once-daily dosage regimens. Children with immunodeficiencies have a shorter t½β of about 16 to 20 hours and a larger volume of distribution. Conversely, in neonates the t½β is prolonged to up to 88 hours.

Therapeutic Use

Patients with AIDS or HIV infection. About 80 to 100% of patients with oropharyngeal/oesophageal candidiasis (candidosis) and approximately 35 to 60% of those with cryptococcal meningitis respond clinically to treatment with fluconazole in dosages up to 400 mg/day for ≤8 weeks, as evidenced in comparative trials. In patients with oropharyngeal candidiasis, fluconazole produced similar rates of clinical success as itraconazole, was at least as effective as clotrimazole troches and was superior to nystatin mouthwash. In patients with oesophageal candidiasis, the largest comparison with ketoconazole demonstrated superior clinical efficacy for fluconazole. However, previous use of ketoconazole may have influenced the results: several other studies indicate clinical response is similar for both drugs. Fluconazole also displayed equivalent clinical efficacy to amphotericin B plus flucytosine in this indication, although the latter trial was small. Patients with cryptococcal meningitis have responded similarly to fluconazole and amphotericin B in 1 trial, but fluconazole appears to eradicate C. neoformans twice as slowly as the polyene and other results have shown fluconazole to be less effective than amphotericin B.

Fluconazole has an established position as secondary prophylaxis against severe and recurrent candidiasis: for example, only 7% of 99 patients relapsed after 6 months’ therapy. In cryptococcal meningitis fluconazole has a preferred role as maintenance therapy following the discontinuation of several large trials favouring fluconazole over the comparator agent. Recrudescence rates were 10-fold less for fluconazole (1.8%) than for amphotericin B (18%) and 6-fold less when compared with itraconazole 200mg/day (3.8 vs 23.6%). The drug has also shown efficacy when used as primary prevention against invasive and superficial fungal infections, perhaps excluding histoplasmosis, and is superior to clotrimazole troches; however, the important issue of possible secondary resistance is of widespread concern and is likely to preclude the routine adoption of this strategy.

Limited investigations indicate that fluconazole achieves clinical cure in about 90% of children with oropharyngeal candidiasis. Results of trials examining the efficacy of fluconazole against histoplasmosis in adults are equivocal.

Pharmacoeconomic analyses based on results of clinical trials suggest improved cost effectiveness for fluconazole, assuming greater efficacy than ketoconazole in the treatment or maintenance therapy of candidiasis, but when equivalent efficacy is assumed ketoconazole appears slightly more cost effective. A similar assumption of equivalent efficacy but superior tolerability compared with amphotericin B has also implied cost advantages for fluconazole in patients with cryptococcal meningitis. Whether these assumptions are valid is a matter of some dispute.

Patients with cancer. As treatment for oropharyngeal/oesophageal candidiasis, fluconazole produces clinical cure rates of about 75 to 80% and mycological eradication rates in the region of 50 to 60%. Fluconazole appeared to be as effective as ketoconazole or as amphotericin B plus flucytosine. About 20% of patients relapse following fluconazole treatment.

As primary prophylaxis in adult patients becoming neutropenic after chemotherapy or bone marrow transplant, fluconazole reduces the incidence of fungal colonisations and superficial candidal infections and lengthens time to amphotericin B therapy, compared with placebo. Systemic infections have decreased in patients undergoing bone marrow transplant but not in those undergoing chemotherapy. The finding that the probability of death decreased in fluconazole compared with placebo recipients in 1 large study in patients undergoing bone marrow transplant is encouraging but requires further corroboration.

Fluconazole is at least as effective as oral polyenes (amphotericin B or nystatin) in preventing infection, although questions remain over study design, but appears superior to clotrimazole troches. Aspergillus infection during fluconazole prophylaxis is infrequent but persistent. Paediatric patients receiving fluconazole as treatment or prophylaxis have shown a similar response to that seen in adults.


Immunocompromised patients tolerate fluconazole therapy well: the clinical profile of types of adverse reactions resembles that seen in immunocompetent patients. There is some evidence of increased incidence of adverse effects in patients with AIDS, with the manufacturer reporting a frequency of 21% compared with 13% in HIV-negative individuals. Variable figures recorded among clinical trials may not give a true picture because of patient and concomitant disease factors.

Gastrointestinal complaints (nausea and vomiting, abdominal pain, diarrhoea), headache and skin rash are experienced most often. Infrequently, gastrointestinal and dermatological events may be severe enough to halt therapy. Exfoliative skin reactions, while rare, require immediate treatment cessation. Hepatic enzyme levels are estimated to rise in <5% of the general population receiving fluconazole and in isolated instances have been associated with clinical symptoms of hepatotoxicity. Patients with cancer and paediatric patients have also tolerated fluconazole well. As shown in comparative studies the tolerability of fluconazole is better than that of amphotericin B and similar to that of ketoconazole.

Drug Interactions

Several drug interactions are of particular interest in the management of immunocompromised patients. Rifampicin (rifampin), but not rifabutin, accelerates fluconazole elimination which may cause clinical failure of the antifungal drug. On the other hand, fluconazole increases plasma concentrations of rifabutin, zidovudine and cyclosporin. Fluconazole also increases the t½β of warfarin and the plasma concentrations of phenytoin and sulphonylurea drugs, with clinical consequences in some cases (increased bleeding, CNS toxicity and hypoglycaemia, respectively). Patients receiving these medications concomitantly with fluconazole should be monitored carefully for unwanted effects of these agents.

Dosage and Administration

All doses are administered once daily and are interchangeable for oral and intravenous formulations. The manufacturer’s prescribing information recommends dosage adjustment in patients with renal impairment. US guidelines. For patients with oropharyngeal or oesophageal candidiasis, 200mg on day 1 then 100mg daily is given for at least 2 weeks. Patients with oesophageal infection should receive the drug for a minimum of 3 weeks and for 2 weeks following symptom resolution: the maximum dosage is 400 mg/day. A dosage of 400 mg/day has been used for patients with systemic candidiasis in clinical trials.

For patients with cryptococcal meningitis, the dosage is 400mg on day 1 then 200mg daily for 10 to 12 weeks after CSF culture is negative. Patients unresponsive to 200 mg/day may receive 400 mg/day. The recommended maintenance dosage of fluconazole is 200 mg/day.

Recommended dosages have not been established for children.

UK guidelines. For oropharyngeal candidiasis the usual dosage is 50mg daily for 7 to 14 days. Dosage is the same for oesophageal infection but the duration is longer (14 to 30 days). A 100mg dosage may be used in difficult infections. For candidaemia and other invasive candidal infection, the dosage is 400mg on day 1 then 200mg daily.

Patients with cryptococcal infections should receive 400mg on day 1 followed by 200 to 400mg daily for at least 6 to 8 weeks. For maintenance therapy fluconazole 100 to 200 mg/day is given indefinitely.

As prophylaxis in patients at risk of becoming neutropenic due to chemotherapy or radiotherapy, the dosage is 50 to 400mg daily, based on the patient’s risk of developing infection.

Children older than 4 weeks should receive 3 mg/kg/day for mucosal candidiasis, 6 to 12 mg/kg/day for systemic candidiasis and cryptococcal infection and 3 to 12 mg/kg/day for prevention of fungal infections due to neutropenia associated with chemotherapy or radiotherapy. Neonates aged 2 weeks or younger should receive the same dosages but at 72 hour intervals, while in those aged 2 to 4 weeks the interval should be 48 hours.


Adis International Limited Fluconazole Itraconazole Candidiasis Ketoconazole 
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.
    Grant SM, Clissold SP. Fluconazole: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial and systemic mycoses. Drugs 1990; 39: 877–916PubMedCrossRefGoogle Scholar
  2. 2.
    Perry CM, Whittington R, McTavish D. Fluconazole: an update of its antimicrobial activity, pharmacokinetic properties and therapeutic use in vaginal candidiasis. Drugs 1995; 49(6): 984–1006PubMedCrossRefGoogle Scholar
  3. 3.
    British Society for Antimicrobial Chemotherapy Working Party. Antifungal chemotherapy in patients with acquired immunodeficiency syndrome. Lancet 1992; 340: 648–51Google Scholar
  4. 4.
    Wingard JR. Importance of Candida species other than C. albicans as pathogens in oncology patients. Clin Infect Dis 1995; 20: 115–25PubMedCrossRefGoogle Scholar
  5. 5.
    Winston DJ, Chandrasekar PH, Lazarus HM, et al. Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, doubleblind, multicenter trial. Ann Intern Med 1993; 118: 495–503PubMedGoogle Scholar
  6. 6.
    Milliken ST, Powles RL. Antifungal prophylaxis in bone marrow transplantation. Rev Infect Dis 1990 Mar; 12 Suppl. 3: S374–9PubMedCrossRefGoogle Scholar
  7. 7.
    Stevens DA. Coccidioidmycosis. N Engl J Med 1995; 332(16): 1077–82PubMedCrossRefGoogle Scholar
  8. 8.
    Pfaller MA, Dupont B, Kobayashi GS, et al. Standardized susceptibility testing of fluconazole: an International Collaborative study. Antimicrob Agents Chemother 1992; 36: 1805–9PubMedCrossRefGoogle Scholar
  9. 9.
    Mañez R, Martin M, Raman V, et al. Fluconazole therapy intransplant recipients receiving FK506. Transplantation 1994; 57: 1521–3PubMedGoogle Scholar
  10. 10.
    Pfaller MA, Vu Q, Lancaster M, et al. Multisite reproducibility of colorimetric broth microdilution method for antifungal susceptibility testing of yeast isolates. J Clin Microbiol 1994; 32: 1625–8PubMedGoogle Scholar
  11. 11.
    Pfaller MA, Grant C, Morthland V, et al. Comparative evaluation of alternative methods for broth dilution susceptibility testing of fluconazole against Candida albicans. J Clin Microbiol 1994; 32: 506–9PubMedGoogle Scholar
  12. 12.
    Rex JH, Pfaller MA, Barry AL, et al. Antifungal susceptibility testing of isolates from a randomized, multicenter trial of fluconazole verusus amphotericin B as treatment of nonneutropenic patients with candidemia. Antimicrob Agents Chemother 1995; 39(1): 40–4PubMedCrossRefGoogle Scholar
  13. 13.
    Pfaller MA, Bale M, Buschelman B, et al. Selection of candidate quality control isolates and tentative quality control ranges for in vitro susceptibility testing of yeast isolates by National Committee for Clinical Laboratory Standards proposed standard methods. J Clin Microbiol 1994; 32: 1650–3PubMedGoogle Scholar
  14. 14.
    Rodriguez-Tudela JL, Martinez-Suarez JV. Improved medium for fluconazole susceptibility testing of Candida albicans. Antimicrob Agents Chemother 1994; 38: 45–8PubMedCrossRefGoogle Scholar
  15. 15.
    Espinel-Ingroff A, Steele-Moore L. Comparison of fluconazole minimum inhibitory concentrations in three different formulations of RPMI-1640. Diagn Microbiol Infect Dis 1994; 20: 87–91PubMedCrossRefGoogle Scholar
  16. 16.
    Espinel-Ingroff A, Steele-Moore L, Galgiani JN. Evaluation of 80% inhibition standards for the determination of fluconazole minimum inhibitory concentrations in three laboratories. Diagn Microbiol Infect Dis 1994; 20: 81–6PubMedCrossRefGoogle Scholar
  17. 17.
    Anaissie EF, Karyotakis NC, Hachem R, et al. Correlation between in vitro and in vivo activity of antifungal agents against Candida species. J Infect Dis 1994; 170: 384–9PubMedCrossRefGoogle Scholar
  18. 18.
    Ruhnke M, Eigler A, Tennagen I, et al. Emergence of fluconazole-resistant strains of Candida albicans in patients with recurrent oropharyngeal candidosis and human immunodeficiency virus infection. J Clin Microbiol 1994; 32(9): 2092–8PubMedGoogle Scholar
  19. 19.
    Baily GG, Perry FM, Denning DW, et al. Fluconazole-resistant candidosis in an HIV cohort. AIDS 1994; 8: 787–92PubMedCrossRefGoogle Scholar
  20. 20.
    Troillet N, Durussel C, Bille J, et al. Correlation between in vitro susceptibility of Candida albicans and fluconazole-resistant oropharyngeal candidiasis in HIV-infected patients. Eur J Clin Microbiol Infect Dis 1993; 12(12): 911–5PubMedCrossRefGoogle Scholar
  21. 21.
    Rodríguez-Tudela JL, Martínez-Suárez JV, Dronda F, et al. Correlation of in-vitro susceptibility test results with clinical response: a study of azole therapy in AIDS patients. J Antimicrob Chemother 1995; 35: 793–804PubMedCrossRefGoogle Scholar
  22. 22.
    Cameron ML, Schell WA, Bruch S, et al. Correlation of m vitro fluconazole resistance of Candida isolates in relation to therapy and symptoms of individuals seropositive for human immunodeficiency virus type 1. Antimicrob Agents Chemother 1993; 37: 2449–53PubMedCrossRefGoogle Scholar
  23. 23.
    Dermoumi H. In vitro susceptibility of fungal isolates of clinically important specimens to itraconazole, fluconazole and amphotericin B. Chemotherapy Basel 1994; 40: 92–8CrossRefGoogle Scholar
  24. 24.
    Slavin MA, Osborne B, Adams R, et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation — a prospective, randomized, double-blind study. J Infect Dis 1995; 171: 1545–52PubMedCrossRefGoogle Scholar
  25. 25.
    Wingard JR, Merz WG, Rinaldi MG, et al. Association of Torulopsis glabrata infections with fluconazole prophylaxis in neutropenic bone marrow transplant patients. Antimicrob Agents Chemother 1993; 37: 1847–9PubMedCrossRefGoogle Scholar
  26. 26.
    Ohkawa M, Tokunaga S, Takashima M, et al. In vitro susceptibility testing of Candida isolates from clinical specimens to four antifungal agents. Chemotherapy 1990; 36: 396–402PubMedCrossRefGoogle Scholar
  27. 27.
    Morace G, Manzara S, Dettori G. In vitro susceptibility of 119 yeast isolates to fluconazole, 5-fluorocytosine, amphotericin B and ketoconazole. Chemotherapy Basel 1991; 37: 23–31CrossRefGoogle Scholar
  28. 28.
    Guinet R, Marlier H. Comparative sensitivity of yeasts to ketoconazole, itraconazole and fluconazole with a liquid medium standardized micromethod [in French]. Pathol Biol 1990; 38: 575–8PubMedGoogle Scholar
  29. 29.
    Price MF, LaRocco MT, Gentry LO. Fluconazole susceptibilities of Candida species and distribution of species recovered from blood cultures over a 5-year period. Antimicrob Agents Chemother 1994; 38: 1422–4PubMedCrossRefGoogle Scholar
  30. 30.
    Yamaguchi H, Uchida K. In vitro susceptibility to fluconazole of fungal strains freshly isolated from child patients with deep-seated mycoses [in Japanese]. Jpn J Antibiot 1993; 46: 647–53PubMedCrossRefGoogle Scholar
  31. 31.
    Van Etten EWM, van den Heuvel-de Groot C, Bakker-Woudenberg AJM. Efficacies of amphotericin B-desoxychol-ate (Fungizone), liposomal amphotericin B (AmBisome) and fluconazole in the treatment of systemic candidosis in immunocompetent and leucopenic mice. J Antimicrob Chemother 1993; 32: 723–39PubMedCrossRefGoogle Scholar
  32. 32.
    Walsh TJ, Aoki S, Mechinaud F, et al. Effects of preventive, early, and late antifungal chemotherapy with fluconazole in different granulocytopenic models of experimental disseminated candidiasis. J Infect Dis 1990; 161: 755–60PubMedCrossRefGoogle Scholar
  33. 33.
    Cacciapuoti A, Loebenberg D, Parmegiani R, et al. Comparison of SCH 39304, fluconazole, and ketoconazole for treatment of systemic infections in mice. Antimicrob Agents Chemother 1992; 36: 64–7PubMedCrossRefGoogle Scholar
  34. 34.
    Bannatyne RM, Cheng PC, Fong IW. Comparison of the efficacy of cilofungin, fluconazole and amphotericin B in the treatment of systemic Candida albicans infection in the neutropenic mouse. Infection 1992; 20: 168–70PubMedCrossRefGoogle Scholar
  35. 35.
    Özgünes I, Usluer G, Giirer F, et al. Efficacy of prophylactic and early fluconazole treatment on systemic candidiasis in experimentally neutropenic rabbits. Chemotherapy Basel 1993; 39: 189–96Google Scholar
  36. 36.
    Kobayashi GS, Travis SJ, Medoff G. Comparison of fluconazole with amphotericin B in treatment of histoplasmosis in normal and immunosuppressed mice. Rev Infect Dis 1990 Mar; 12 Suppl. 3: S291–3PubMedCrossRefGoogle Scholar
  37. 37.
    Allendoerfer R, Marquis AJ, Rinaldi MG, et al. Combined therapy with fluconazole and flucytosine in murine cryptococcal meningitis. Antimicrob Agents Chemother 1991; 35: 726–9PubMedCrossRefGoogle Scholar
  38. 38.
    Karyotakis NC, Anaissie EJ, Hachem R, et al. Comparison of the efficacy of polyenes and triazoles against hematogenous Candida krusei infection in neutropenic mice. J Infect Dis 1993; 168: 1311–3PubMedCrossRefGoogle Scholar
  39. 39.
    Rex JH, Rinaldi MG, Pfaller MA. Resistance of Candida species to fluconazole. Antimicrob Agents Chemother 1995; 39(1): 1–8PubMedCrossRefGoogle Scholar
  40. 40.
    Dewsnup DH, Stevens DA. Efficacy of oral amphotericin B in AIDS patients with thrush clinically resistant to fluconazole. J Med Vet Mycol 1994; 32: 389–93PubMedCrossRefGoogle Scholar
  41. 41.
    Redding S, Smith J, Farinacci G, et al. Resistance of Candida albicans to fluconazole during treatment of oropharyngeal candidiasis in a patient with AIDS: documentation by in vitro susceptibility testing and DNA subtype analysis. Clin Infect Dis 1994; 18: 240–2PubMedCrossRefGoogle Scholar
  42. 42.
    Boken DJ, Swindells S, Rinaldi MG. Fluconazole-resistant Candida albicans. Clin Infect Dis 1993; 17: 1018–21PubMedCrossRefGoogle Scholar
  43. 43.
    Heinic GS, Stevens DA, Greenspan D, et al. Fluconazole-resistant Candida in AIDS patients. Oral Surg Oral Med Oral Pathol 1993; 76: 711–5PubMedCrossRefGoogle Scholar
  44. 44.
    Fox R, Neal KR, Leen CL, et al. Fluconazole resistant Candida in AIDS [letter; comment]. J Infect 1991; 22: 201–4PubMedCrossRefGoogle Scholar
  45. 45.
    Sanguineti A, Carmichael JK, Campbell K. Fluconazole-resistant Candida albicans after long-term suppressive therapy. Arch Intern Med 1993; 153: 1122–4PubMedCrossRefGoogle Scholar
  46. 46.
    Smith D, Boag F, Midgley J, et al. Fluconazole resistant Candida in AIDS. J Infect 1991; 23: 345–6PubMedCrossRefGoogle Scholar
  47. 47.
    Willocks L, Leen CLS, Brettle RP, et al. Fluconazole resistance in AIDS patients. J Antimicrob Chemother 1991; 28: 937–9PubMedCrossRefGoogle Scholar
  48. 48.
    Newman SL, Flanigan TP, Fisher A, et al. Clinically significant mucosal candidiasis resistant to fluconazole treatment in patients with AIDS. Clin Infect Dis 1994; 19: 684–6PubMedCrossRefGoogle Scholar
  49. 49.
    Diz P, Ocampo A, Miralies C, et al. Oro-esophageal candidiasis resistant to fluconazole in patients with AIDS [in Spanish]. Enferm Infecc Microbiol Clin 1993; 11: 36–9PubMedGoogle Scholar
  50. 50.
    Kitchen VS, Savage M, Harris JR. Candida albicans resistance in AIDS [letter] [see comments]. J Infect 1991; 22: 204–5PubMedCrossRefGoogle Scholar
  51. 51.
    Ruhnke M, Eigler A, Engelmann E, et al. Correlation between antifungal susceptibility testing of Candida isolates from patients with HIV infection and clinical results after treatment with fluconazole. Infection 1994; 22(2): 72/132–6/136Google Scholar
  52. 52.
    Johnson EM, Warnock DW, Luker J, et al. Emergence of azole drug resistance in Candida species from HIV-infected patients receiving prolonged fluconazole therapy for oral candidosis. J Antimicrob Chemother 1995; 35: 103–14PubMedCrossRefGoogle Scholar
  53. 53.
    Bart-Delabesse E, Boiron P, Carlotti A, et al. Candida albicans genotyping in studies with patients with AIDS developing resistance to fluconazole. J Clin Microbiol 1993; 31: 2933–7PubMedGoogle Scholar
  54. 54.
    Lischewski A, Ruhnke M, Tennagen I, et al. Molecular epidemiology of Candida isolates from AIDS patients showing different fluconazole resistance profiles. J Clin Microbiol 1995; 33(3): 769–71PubMedGoogle Scholar
  55. 55.
    Barchiesi F, Hollis RJ, McGough DA, et al. DNA subtypes and fluconazole susceptibilities of Candida albicans isolates from the oral cavities of patients with AIDS. Clin Infect Dis 1995; 20: 634–40PubMedCrossRefGoogle Scholar
  56. 56.
    Paugam A, Dupouy-Camet J, Blanche P, et al. Increased fluconazole resistance of Cryptococcus neoformans isolated from a patient with AIDS and recurrent meningitis. Clin Infect Dis 1994; 19: 975–6PubMedCrossRefGoogle Scholar
  57. 57.
    Peetermans W, Bobbaers H, Verhaegen J, et al. Fluconazole-resistant Cryptococcus neoformans var gattii in an AIDS patient. Acta Clin Belg 1993; 48: 405–9PubMedGoogle Scholar
  58. 58.
    Coker RJ, Harris JRW. Failure of fluconazole treatment in cryptococcal meningitis despite adequate CSF levels. J Infect 1991; 23: 101–3PubMedCrossRefGoogle Scholar
  59. 59.
    Casasnovas R-O, Caillot D, Solary E, et al. Prophylactic fluconazole and Candida krusei infections. N Engl J Med 1992; 326: 891–2PubMedCrossRefGoogle Scholar
  60. 60.
    Hoppe JE, Klingebiel T, Niethammer D. Selection of Candida glabrata in pdiatric bone marrow transplant recipients receiving fluconazole. Pediatr Hematol Oncol 1994; 11: 207–10PubMedCrossRefGoogle Scholar
  61. 61.
    Mcllroy MA. Failure of fluconazole to suppress fungemia in a patient with fever, neutropenia, and typhlitis. J Infect Dis 1991; 163: 420–1CrossRefGoogle Scholar
  62. 62.
    Bignardi GE, Savage MA, Coker R, et al. Fluconazole and Candida krusei infections. J Hosp Infect 1991; 18: 326–7PubMedCrossRefGoogle Scholar
  63. 63.
    Akova M, Akalin HE, Uzun ö, et al. Emergence of Candida krusei infections after therapy of oropharyngeal candidiasis with fluconazole [letter]. Eur J Clin Microbiol Infect Dis 1991; 10: 598–9PubMedCrossRefGoogle Scholar
  64. 64.
    Wingard JR, Merz WG, Rinaldi MG, et al. Increase in Candida krusei infection among patients with bone marrow transplan-tation and neutropenia treated prophylactically with fluconazole. N Engl J Med 1991; 325: 1274–7PubMedCrossRefGoogle Scholar
  65. 65.
    Goodman JL, Winston DJ, Greenfield RA, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 1992; 326: 845–51PubMedCrossRefGoogle Scholar
  66. 66.
    Sugar AM, Tija J. Effect of fluconazole on the interactions between human neutrophils and Candida albicans. Int J Antimicrob Agents 1993; 3: 171–3PubMedCrossRefGoogle Scholar
  67. 67.
    Odds FC, Webster CE. Effects of azole antifungals in vitro on host/parasite interactions relevant to Candida infections. J Antimicrob Chemother 1988; 22: 473–81PubMedCrossRefGoogle Scholar
  68. 68.
    Senior DS, Shaw JTP. In vitro effects of fluconazole (UK-49,858) and ketoconazole on mouse lymphocyte proliferation and on Candida blastospore destruction by human polymor-phonuclear leukocytes. Int J Immunopharmacol 1988; 10: 169–73PubMedCrossRefGoogle Scholar
  69. 69.
    Barantsevitch EP, Pastushenkov VL. Immunometabolic monitoring in patients with candidosis treated with fluconazole [abstract]. International J Immunorehabilitation 1994; 48(1) Suppl.: 48Google Scholar
  70. 70.
    Vuddhakul V, Mai GT, McCormack JG, et al. Suppression of neutrophil and lymphoproliferative responses in vitro by itraconazole but not fluconazole. Int J Immunopharmacol 1990; 12(6): 639–45PubMedCrossRefGoogle Scholar
  71. 71.
    Pawelec G, Ehninger G, Rehbein A, et al. Comparison of the immunosuppressive activities of the antimycotic agents itraconazole, fluconazole, ketoconazole and miconazole on human T-cells. Int J Immunopharmacol 1991; 13(2-3): 299–304PubMedCrossRefGoogle Scholar
  72. 72.
    Drummond DC, Wong CW, Whitman LM, et al. The effect of amphotericin B, miconazole and fluconazole on cellular components of the immune system in vivo [abstract]. Aust N Z J Med 1993; 23: 442Google Scholar
  73. 73.
    Como JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. N Engl J Med 1994; 330: 263–72PubMedCrossRefGoogle Scholar
  74. 74.
    Bodey GP. Azole antifungal agents. Clin Infect Dis 1992 Mar; 14 Suppl. 1: S161–9PubMedCrossRefGoogle Scholar
  75. 75.
    Back DJ, Tjia JF, Abel SM. Azoles, allylamines and drug metabolism. Br J Dermatol 1992 Feb; 126 Suppl. 39: 14–8PubMedCrossRefGoogle Scholar
  76. 76.
    Lazar JD, Wilner KD. Drug interactions with fluconazole. Rev Infect Dis 1990 Mar; 12 Suppl. 3: S327–33PubMedCrossRefGoogle Scholar
  77. 77.
    Touchette MA, Chandrasekar PH, Milad MA, et al. Contrasting effects of fluconazole and ketoconazole on phenytoin and testosterone disposition in man. Br J Clin Pharmacol 1992; 34: 75–8PubMedCrossRefGoogle Scholar
  78. 78.
    Gascon MP, Oestreicher-Kondo M, Dayer P. Comparative effects of imidazole antifungals on liver monoxygenases [abstract]. Clin Pharmacol Ther 1991; 49: 158Google Scholar
  79. 79.
    Brammer KW, Farrow PR, Faulkner JK. Pharmacokinetics and tissue penetration of fluconazole in humans. Rev Infect Dis 1990 Mar; 12 Suppl. 3: S318–26PubMedCrossRefGoogle Scholar
  80. 80.
    Debruyne D, Ryckelynck J-P. Clinical pharmacokinetics of fluconazole. Clin Pharmacokinet 1993; 24: 10–27PubMedCrossRefGoogle Scholar
  81. 81.
    DeMuria D, Forrest A, Rich J, et al. Pharmacokinetics and bioavailability of fluconazole in patients with AIDS. Antimicrob Agents Chemother 1993; 37: 2187–92PubMedCrossRefGoogle Scholar
  82. 82.
    Wildfeuer A, Pfaff G, Zimmermann T, et al. Pharmacokinetic profile of fluconazole, a systemic antimycotic drug [in German]. Med Welt 1991; 42: 436–40Google Scholar
  83. 83.
    Yeates RA, Ruhnke M, Pfaff G, et al. The pharmacokinetics of fluconazole after a single intravenous dose in AIDS patients. Br J Clin Pharmacol 1994; 38: 77–9PubMedCrossRefGoogle Scholar
  84. 84.
    Lazo DLVS, Volkow P, Yeates RA, et al. Administration of the antimycotic agents fluconazole and itraconazole to leukaemia patients; a comparative pharmacokinetic study. Drugs Exp Clin Res 1994; 20(2): 69–75Google Scholar
  85. 85.
    Blum RA, D’Andréa DT, Florentino BM, et al. Increased gastric pH and the bioavailability of fluconazole and ketoconazole. Ann Intern Med 1991; 114: 755–7PubMedGoogle Scholar
  86. 86.
    Zimmermann T, Yeates RA, Laufen H, et al. Influence of concomitant food intake on the oral absorption of two triazole antifungal agents, itraconazole and fluconazole. Eur J Clin Pharmacol 1994; 46(2): 147–50PubMedCrossRefGoogle Scholar
  87. 87.
    Thorpe JE, Baker N, Bromet-Petit M. Effect of oral antacid administration on the pharmacokinetics of oral fluconazole. Antimicrob Agents Chemother 1990; 34: 2032–3PubMedCrossRefGoogle Scholar
  88. 88.
    Lim SG, Sawyerr AM, Hudson M, et al. Short report: the absorption of fluconazole and itraconazole under conditions of low intragastric acidity. Aliment Pharmacol Ther 1993; 7: 317–21PubMedCrossRefGoogle Scholar
  89. 89.
    Schäfer-Korting M. Pharmacokinetic optimisation of oral antifungal therapy. Clin Pharmacokinet 1993; 25: 329–41PubMedCrossRefGoogle Scholar
  90. 90.
    Chin T, Fong IW, Vandenbroucke A. Pharmacokinetics of fluconazole in serum and cerebrospinal fluid in a patient with AIDS and cryptococcal meningitis. Pharmacotherapy 1990; 10(4): 305–7PubMedGoogle Scholar
  91. 91.
    van Wout JW, De Graeff-Meeder ER, Paul LC, et al. Treatment of two cases of cryptococcal meningitis with fluconazole. Scand J Infect Dis 1988; 20: 193–8CrossRefGoogle Scholar
  92. 92.
    Garcia-Hermoso D, Dromer F, Improvosi L, et al. Fluconazole concentrations in saliva from AIDS patients with oropharyngeal candidosis refractory to treatment with fluconazole. Antimicrob Agents Chemother 1995; 39(3): 656–60PubMedCrossRefGoogle Scholar
  93. 93.
    Oliary J, Tod M, Louchahi K, et al. Influence of local radiotherapy on penetration of fluconazole into human saliva. Antimicrob Agents Chemother 1993; 37(12): 2674–7PubMedCrossRefGoogle Scholar
  94. 94.
    Ruhnke M, Yeates RA, Pfaff G, et al. Single-dose pharmacokinetics of fluconazole in patients with liver cirrhosis. J Antimicrob Chemother 1995; 35: 641–7PubMedCrossRefGoogle Scholar
  95. 95.
    Brammer KW, Coates PE. Pharmacokinetics of fluconazole in pediatrie patients. Eur J Clin Microbiol Infect Dis 1994; 13: 325–9PubMedCrossRefGoogle Scholar
  96. 96.
    Lee JW, Seibel NL, Amantea M, et al. Safety and pharmacokinetics of fluconazole in children with neoplastic diseases. J Pediatr 1992; 120: 987–93PubMedCrossRefGoogle Scholar
  97. 97.
    Seay RE, Larson TA, Toscano JP, et al. Pharmacokinetics of prophylactic fluconazole in pediatric hematology/oncology patients [abstract]. Pharmacotherapy 1992; 12(3): 246Google Scholar
  98. 98.
    Powderly WG. New developments in the treatment of cryptococcal disease in AIDS. AIDS Clin Rev 1993-94: 113-28Google Scholar
  99. 99.
    Barchiesi F, Giacometti A, Arzeni D, et al. Fluconazole and ketoconazole in the treatment of oral and esophageal candidiasis in AIDS patients. J Chemother 1992; 4: 381–6PubMedGoogle Scholar
  100. 100.
    Garber G. Treatment of oral Candida mucositis infections. Drugs 1994; 5: 734–40CrossRefGoogle Scholar
  101. 101.
    Harkness J, Marriott D, Fulton W, et al. An open assessment of the safety and efficacy of oral fluconazole in the treatment of oropharyngeal candidiasis in HIV infected patients [abstract]. Aust N Z J Med 1990 Jun; 20 Suppl.: 436Google Scholar
  102. 102.
    Just-Nubling G, Gentschew G, Dohle M, et al. Fluconazole in the treatment of oropharyngeal candidosis in HIV-positive patients. Mycoses 1990; 33: 435–40PubMedGoogle Scholar
  103. 103.
    Plettenberg A, Stoehr A, Höffken G, et al. Fluconazole therapy of oral candidiasis in HIV-infected patients: results of a multicentre study. Infection 1994; 22: 118–23PubMedCrossRefGoogle Scholar
  104. 104.
    Sarnow E, Baranowski E, Bauer G, et al. Oropharyngeal candidiasis in HIV-positive patients. Fluconazole in the treatment in registered practice [in German]. Munch Med Wochenschr 1992; 134: 85–7Google Scholar
  105. 105.
    Hernández-Sampelayo T, Multicentre Study Group, et al. Fluconazole versus ketoconazole in the treatment of oropharyngeal candidiasis in HIV-infected children. Eur J Clin Microbiol Infect Dis 1994; 13: 340–4PubMedCrossRefGoogle Scholar
  106. 106.
    Brockmeyer NH, Hantschke D, Olbricht T, et al. Fluconazole or amphotericin B and flucytosine in the treatment of Candida oesophagitis in HIV-1-infected patients [in German]. Mycoses 1991; 34 Suppl. 1: 83–6PubMedGoogle Scholar
  107. 107.
    Pons V, Greenspan D, Debruin M, et al. Therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, prospective multicenter study of oral fluconazole versus clotrimazole troches. J Acquir Immune Defic Syndr 1993; 6: 1311–6PubMedGoogle Scholar
  108. 108.
    Esposito R, Uberti Foppa C, Cernuschi M. Treatment of HIV+ patients with oropharyngeal and/or oesophageal candidiasis: results of a d.b. study [abstract no. Th.BP348]. 5th International Conference on AIDS, Montreal, Canada, Jun 4-9,1989Google Scholar
  109. 109.
    De Wit S, Goossens H, Weerts D, et al. Comparison of fluconazole and ketoconazole for oropharyngeal candidiasis in AIDS. Lancet 1989; 1: 746–7PubMedCrossRefGoogle Scholar
  110. 110.
    Gritti FM, Raise E, Vannini V, et al. Fluconazole treatment for fungal infections in ARC and AIDS [abstract no. MBP 96]. 5th International Conference on AIDS, Montreal, Canada, June 4-9,1989.Google Scholar
  111. 111.
    Laine L, Dretler RH, Conteas CN, et al. Fluconazole compared with ketoconazole for the treatment of Candida esophagitis in AIDS. Arandomized trial. Ann Intern Med 1992; 117: 655–60PubMedGoogle Scholar
  112. 112.
    Frechette G, De Beule K, Weinke W, et al. Effects of itraconazole in the treatment of oral candidosis in HIV patients. A double-blind, double-dummy, randomized comparison with fluconazole [abstract no. 1219]. Abstracts of the 35th ICAAC, 1995: 244Google Scholar
  113. 113.
    Graybill JR, Vazquez J, Darouiche RO, et al. Itraconazole oral solution (IS) versus fluconazole (F) treatment of oropharyn-geal candidiasis (OC) [abstract no. 1009]. Abstracts of the 35th ICAAC, 1995:244Google Scholar
  114. 114.
    Pons V, Greenspan D, Gallant J, et al. Comparative clinical study of oral suspension fluconazole versus topical liquid oral nystatin in the treatment of oropharyngeal candidiasis in AIDS [abstract no. 1221a]. Abstracts of the 35th ICAAC, 1995 (p 244).Google Scholar
  115. 115.
    Larsen RA, Leal MAE, Chan LS. Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS. A randomized trial. Ann Intern Med 1990; 113: 183–7PubMedGoogle Scholar
  116. 116.
    Saag MS, Powderly WG, Cloud GA. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-asso-ciated crytococcal meningitis. N Engl J Med 1992; 326: 83–9PubMedCrossRefGoogle Scholar
  117. 117.
    Rabeneck L, Laine L. Eosphageal candidiasis in patients infected with the human immunodeficiency virus. A decision analysis to assess cost-effectiveness of alternative management strategies. Arch Intern Med 1994; 154: 2705–10PubMedCrossRefGoogle Scholar
  118. 118.
    Centers for Disease Control and Prevention. USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: a summary. MMWR Morb Mortal Wkly Rep 1995; 44(no. RR-8): 1–34Google Scholar
  119. 119.
    Agresti MG, de Bernardis F, Mondello F, et al. Clinical and mycological evaluation of fluconazole in the secondary prophylaxis of esophageal candidiasis in AIDS patients: an open, multicenter study. Eur J Epidemiol 1994; 10: 17–22PubMedCrossRefGoogle Scholar
  120. 120.
    Just-Nubling G, Gentschew G, Meissner K, et al. Fluconazole prophylaxis of recurrent oral candidiasis in HIV-positive patients. Eur J Clin Microbiol Infect Dis 1991; 10: 917–21PubMedCrossRefGoogle Scholar
  121. 121.
    Powderly WG, Finkelstein DM, Feinberg J, et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. N Engl J Med 1995; 332: 700–5PubMedCrossRefGoogle Scholar
  122. 122.
    Marchisio P, Principi N. Treatment of oropharyngeal candidiasis in HIV-infected children with oral fluconazole. Eur J Clin Microbiol Infect Dis 1994; 13: 338–40PubMedCrossRefGoogle Scholar
  123. 123.
    Powderly WG. Cryptococcal meningitis and AIDS. Clin Infect Dis 1993; 17: 837–42PubMedCrossRefGoogle Scholar
  124. 124.
    Bozzette SA, Larsen RA, Chiu J, et al. Fluconazole treatment of persistent Cryptococus neoformans prostatic infection in AIDS. Ann Intern Med 1991; 115: 285–6PubMedGoogle Scholar
  125. 125.
    Laroche R, DuPont B, Touze JE, et al. Cryptococcal meningitis associated with acquired immunodeficiency syndrome (AIDS) in African patients — treatment with fluconazole. J Med Vet Mycol 1992; 30(1): 71–8PubMedCrossRefGoogle Scholar
  126. 126.
    Haubrich RH, Haghighat D, Bozzette SA, et al. High-dose fluconazole for treatment of cryptococcal disease in patients with human immunodeficiency virus infection. J Infect Dis 1994; 170: 238–42PubMedCrossRefGoogle Scholar
  127. 127.
    Berry AJ, Rinaldi MG, Graybill JR. Use of high-dose fluconazole as salvage therapy for cryptococcal meningitis in patients with AIDS. Antimicrob Agents Chemother 1992; 36: 690–2PubMedCrossRefGoogle Scholar
  128. 128.
    Dismukes WE. Management of cryptococcosis. Clin Infect Dis 1993 Nov; 17 Suppl. 2: 507–12CrossRefGoogle Scholar
  129. 129.
    Bozzette SA, Larsen RA, Chiu J, et al. A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. N Engl J Med 1991; 324: 580–4PubMedCrossRefGoogle Scholar
  130. 130.
    Powderly WG, Saag MS, Cloud GA, et al. A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. N Engl J Med 1992; 326: 793–8PubMedCrossRefGoogle Scholar
  131. 131.
    Saag MS, Cloud GC, Graybill JR, et al. Comparison of fluconazole (FLU) versus itraconazole (ITRA) as maintenance therapy of AIDS-associated cryptococcal meningitis [abstract no. 1218]. Abstracts of the 35th ICAAC, 1995: 244Google Scholar
  132. 132.
    Nightingale SD, Cal SX, Peterson DM, et al. Primary prophylaxis with fluconazole against systemic fungal infections in HIV-positive patients. AIDS 1992; 6: 191–4PubMedCrossRefGoogle Scholar
  133. 133.
    Buxton MJ, Dubois DJ, Turner RR, et al. Cost implications of alternative treatments for AIDS patients with cryptococcal meningitis. Comparison of fluconazole and amphotericin B-based therapies. J Infect 1991; 23: 17–31PubMedCrossRefGoogle Scholar
  134. 134.
    Denning DW. Cost implications of alternative treatments for AIDS patients with cryptococcal meningitis [letter]. J Infect 1992; 24: 212–3PubMedCrossRefGoogle Scholar
  135. 135.
    Quagliarello VJ, Viscoli C, Horwitz RI. Primary prevention of cryptococcal meningitis by fluconazole in HIV-infected patients. Lancet 1995; 345: 548–52PubMedCrossRefGoogle Scholar
  136. 136.
    Wheat L, Mawhinney S, Hafner R, et al. Fluconazole treatment for histoplasmosis in AIDS: prospective multicenter noncomparative trial [abstract no. 1233]. Abstracts of the 34th ICAAC, 1994Google Scholar
  137. 137.
    Sharkey-Mathis PK, Velez J, Fetchick R, et al. Histoplasmosis in the acquired immunodeficiency syndrome (AIDS): treatment with itraconazole and fluconazole. J Acquir Immune Defic Syndr 1993; 6: 809–19PubMedGoogle Scholar
  138. 138.
    Norris S, Wheat J, McKinsey D, et al. Prevention of relapse of histoplasmosis with fluconazole in patients with the acquired immunodeficiency syndrome. Am J Med 1994; 96: 504–8PubMedCrossRefGoogle Scholar
  139. 139.
    Tolkoff-Rubin NE, Conti DJ, Doran M, et al. Fluconazole in the treatment of invasive candidal and cryptococcal infections in organ transplant recipients. Pharmacotherapy 1990; 10(6): 159S–63SPubMedGoogle Scholar
  140. 140.
    Bren A, Kandus A, Lindic J, et al. Fluconazole in the treatment of fungal infections in kidney-transplanted patients. Transplant Proc 1992; 24: 2765–6PubMedGoogle Scholar
  141. 141.
    Akova M, Akalin HE, Uzun Ö, et al. Efficacy of fluconazole in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer: factors influencing the outcome. Clin Infect Dis 1994; 18: 298–304PubMedCrossRefGoogle Scholar
  142. 142.
    Krcméry Jr V, Koza I, Hornikova M, et al. Fluconazole in the treatment of mycotic oropharyngeal stomatitis and esophagitis in neutropenic cancer patients. Chemotherapy Basel 1991; 37: 343–5Google Scholar
  143. 143.
    Graninger W, Presteril E, Schneeweiss B, et al. Treatment of Candida albicans fungaemia with fluconazole. J Infect 1993; 26: 133–46PubMedCrossRefGoogle Scholar
  144. 144.
    Anaissie E, Bodey GP, Kantarjian H, et al. Fluconazole therapy for chronic disseminated candidiasis in patients with leukemia and prior amphotericin B therapy. Am J Med 1991; 91: 142–50PubMedCrossRefGoogle Scholar
  145. 145.
    Kauffman CA, Bradley SF, Ross SC, et al. Hepatosplenic candidiasis: successful treatment with fluconazole. Am J Med 1991; 91: 137–41PubMedCrossRefGoogle Scholar
  146. 146.
    Meunier F, Aoun M, Gerard M. Therapy for oropharyngeal candidiasis in the immunocompromised host: a randomized double-blind study of fluconazole vs. ketoconazole. Rev Infect Dis 1990 Mar; 12 Suppl. 3: S364–8PubMedCrossRefGoogle Scholar
  147. 147.
    Rex JH, Bennett JE, Sugar AM, et. al. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. N Engl J Med 1994; 331(20): 1325–30PubMedCrossRefGoogle Scholar
  148. 148.
    Anaissie EJ, Darwiche R, Mera J, et al. A prospective randomized multicenter study comparing fluconazole to amphotericin B for nosocomial candidiasis [abstract no. 808]. Abstracts of the 33 rd ICAAC, 1993.Google Scholar
  149. 149.
    Silling-Engelhardt G, Fegeler W, Roos N, et al. Interventional treatment of unexplained fever (FUO) and documented infections in neutropenic patients with hématologic malignancies: fluconazole versus ampho-B/5-FC [abstract]. Onkologie 1991 Oct; 14 Suppl. 2: 155Google Scholar
  150. 150.
    Ellis ME, Halim MA, Spence D, et al. Systemic amphotericin B versus fluconazole in the management of antibiotic resistant neutropenic fever — preliminary observations from a pilot, exploratory study. J Infect 1995; 30: 141–6PubMedCrossRefGoogle Scholar
  151. 151.
    Samonis G, Rolston K, Karl C, et al. Prophylaxis of oropharyngeal candidiasis with fluconazole. Rev Infect Dis 1990 Mar; 12 Suppl. 3: S369–73PubMedCrossRefGoogle Scholar
  152. 152.
    Huijgens PC, van Loenen AC, Simoons-Smit AM, et al. The prophylactic use of fluconazole 50 vs. 100 mg daily in haematological malignancies [letter]. Eur J Cancer 1993; 29A: 926–7PubMedCrossRefGoogle Scholar
  153. 153.
    Bodey GP, Anaissie EJ, Elting LS, et al. Antifungal prophylaxis during remission induction therapy for acute leukemia: fluconazole versus intravenous amphotericin B. Cancer 1994; 73: 2099–106PubMedCrossRefGoogle Scholar
  154. 154.
    Menichetti F, Del Favero A, Martino P, et al. Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B. Ann Intern Med 1994; 120: 913–8PubMedGoogle Scholar
  155. 155.
    Meunier F, Aoun M, Janssens M, et al. Chemoprophylaxis of fungal infections in granulocytopenic patients using fluconazole vs oral amphotericin B. Drug Invest 1991; 3(4): 258–65Google Scholar
  156. 156.
    Philpott-Howard JN, Wade JJ, Mufti GJ, et al. Randomized comparison of oral fluconazole versus oral polyenes for the prevention of fungal infection in patients at risk of neutropenia. J Antimicrob Chemother 1993; 31: 973–84PubMedCrossRefGoogle Scholar
  157. 157.
    Ninane J, Multicentre Study Group, et al. A multicentre study of fluconazole versus oral polyenes in the prevention of fungal infection in children with hematological or oncological malignancies. Eur J Clin Microbiol Infect Dis 1994; 13: 330–7PubMedCrossRefGoogle Scholar
  158. 158.
    Ellis ME, Clink H, Ernst P, et al. Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients. Eur J Clin Microbiol Infect Dis 1994; 13: 3–11PubMedCrossRefGoogle Scholar
  159. 159.
    Kappe R, Osterziel KJ, Rüchel R, et al. Fluconazole in patients at risk from invasive aspergillosis. J Med Vet Mycol 1993; 31: 259–61PubMedCrossRefGoogle Scholar
  160. 160.
    Meis JF, Donnelly JP, Hoogkamp-Korstanje JA, et al. Aspergillus fumigatus pneumonia in neutropenic patients during therapy with fluconazole for infection due to Candida species. Clin Infect Dis 1993; 16: 734–5PubMedCrossRefGoogle Scholar
  161. 161.
    Viscoli C, Castagnola E, Fioredda F, et al. Fluconazole in the treatment of candidiasis in immunocompromised children. Antimicrob Agents Chemother 1991; 35: 365–7PubMedCrossRefGoogle Scholar
  162. 162.
    Fasano C, O’Keeffe J, Gibbs D. Fluconazole treatment of children with severe fungal infections not treatable with conventional agents. Eur J Clin Microbiol Infect Dis 1994; 13: 344–7PubMedCrossRefGoogle Scholar
  163. 163.
    Cesaro S, Rossetti F, Perilongo G, et al. Fluconazole prophylaxis and Candida fungemia in neutropenic children with malignancies. Haematologica 1993; 78: 249–51PubMedGoogle Scholar
  164. 164.
    Cap J, Mojzesova A, Kayserova E, et al. Fluconazole in children: first experience with prophylaxis in chemotherapy-induced neutropenia in pédiatrie patients with cancer. Chemotherapy 1993; 39: 438–42PubMedCrossRefGoogle Scholar
  165. 165.
    Fluconazole prescribing information. Pfizer Limited, USA, 1995.Google Scholar
  166. 166.
    Harb GE, Jacobson MA. Human immunodeficiency virus (HIV) infection. Does it increase susceptibility to adverse drug reactions? Drug Saf 1993; 9: 1–8PubMedCrossRefGoogle Scholar
  167. 167.
    Azón-Masoliver A, Vilaplana J. Fluconazole-induced toxic epidermal necrolysis in a patient with human immunodeficiency virus infection. Dermatology 1993; 187(4): 268–9PubMedCrossRefGoogle Scholar
  168. 168.
    Gussenhoven MJE, Haak A, Peereboom-Wynia JDR, et al. Stevens-Johnson syndrome after fluconazole. Lancet 1991; 338: 120PubMedCrossRefGoogle Scholar
  169. 169.
    Perfect JR, Lindsay MH, Drew RH. Adverse drug reactions to systemic antifungals. Prevention and management. Drug Saf 1992; 7: 323–63PubMedCrossRefGoogle Scholar
  170. 170.
    Munoz P, Moreno S, Berenguer J, et al. Fluconazole-related hepatotoxicity in patients with acquired immunodeficiency syndrome. Arch Intern Med 1991; 151: 1020–1PubMedCrossRefGoogle Scholar
  171. 171.
    Wells C, Lever AML. Dose-dependent fluconazole heptatotoxcity proven on biopsy and rechallenge. J Infect 1992; 24: 111–2PubMedCrossRefGoogle Scholar
  172. 172.
    Jacobson MA, Hanks DK, Ferrell LD. Fatal acute hepatic necrosis due to fluconazole. Am J Med 1994; 96: 188–90PubMedCrossRefGoogle Scholar
  173. 173.
    Gradon JD, Sepkowitz DV. Fluconazole-associated acute adrenal insufficiency. Postgrad Med J 1991; 67: 1084–5PubMedCrossRefGoogle Scholar
  174. 174.
    Apseloff G, Hilligoss DM, Gardner MJ, et al. Induction of fluconazole metabolism by rifampin: in vivo study in humans. J Clin Pharmacol 1991; 31: 358–61PubMedGoogle Scholar
  175. 175.
    Coker RJ, Tomlinson DR, Parkin J, et al. Interaction between fluconazole and rifampicin [letter]. BMJ 1990; 301: 818PubMedCrossRefGoogle Scholar
  176. 176.
    Trapnell CB, Lavelle JP, O’Leary CR, et al. Rifabutin does not alter fluconazole pharmacokinetics [abstract]. Clin Pharmacol Ther 1993; 53: 196Google Scholar
  177. 177.
    Narang PK, Trapnell CB, Schoenfelder JR, et al. Fluconazole and enhanced effect of rifabutin prophylaxis [letter]. N Engl JMed 1994; 330: 1316CrossRefGoogle Scholar
  178. 178.
    Bruzzese VL, Gillum JG, Israel DS, et al. Effect of fluconazole on pharmacokinetics of 2′,3′-dideoxyinosine in persons séropositive for human immunodeficiency virus. Antimicrob Agents Chemother 1995; 39: 1050–3PubMedCrossRefGoogle Scholar
  179. 179.
    Sahai J, Gallicano K, Pakuts A. Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus. J Infect Dis 1994; 169: 1103–7PubMedCrossRefGoogle Scholar
  180. 180.
    Canafax DM, Graves NM, Hilligoss DM, et al. Interaction between cyclosporine and fluconazole in renal allograft recipients. Transplantation 1991; 51: 1014–8PubMedCrossRefGoogle Scholar
  181. 181.
    Muñoz-Sanz A, Cubero J, Caravaca F, et al. Interaction between ciclosporine and fluconazole in a renal transplant [in Spanish]. Rev Esp Quimioter 1992; 5: 352–3Google Scholar
  182. 182.
    López-Gil JA. Fluconazole-cyclosporine interaction: a dosedependent effect? Ann Pharmacother 1993; 27: 427–30PubMedGoogle Scholar
  183. 183.
    Torregrosa V, De la Torre M, Campistol JM, et al. Interaction of fluconazole with ciclosporin A [letter]. Nephron 1992; 60: 125–6PubMedCrossRefGoogle Scholar
  184. 184.
    Black DJ, Gidal BE, Seaton TL, et al. An evaluation of the effect of fluconazole on the stereoselective metabolism of warfarin [abstract]. Clin Pharmacol Ther 1992; 51: 184Google Scholar
  185. 185.
    Gericke KR. Possible interaction between warfarin and fluconazole. Pharmacotherapy 1993; 13: 508–9PubMedGoogle Scholar
  186. 186.
    Crussell-Porter LL, Rindone JP, Ford MA, et al. Low-dose fluconazole therapy potentiates the hypoprothrombinemic response of warfarin sodium. Arch Intern Med 1993; 153: 102–4PubMedCrossRefGoogle Scholar
  187. 187.
    Seaton TL, Celum CL, Black DJ. Possible potentiation of warfarin by fluconazole. DICP 1990; 24: 1177–8PubMedGoogle Scholar
  188. 188.
    Kerr HD. Case report: potentiation of warfarin by fluconazole. Am J Med Sci 1993; 305: 164–5PubMedCrossRefGoogle Scholar
  189. 189.
    Blum RA, Wilton JH, Hilligoss DM, et al. Effect of fluconazole on the disposition of phenytoin. Clin Pharmacol Ther 1991; 49: 420–5PubMedCrossRefGoogle Scholar
  190. 190.
    Howitt KM, Oziemski MA. Phenytoin toxicity induced by fluconazole [letter]. Med J Aust 1989; 151: 603–4PubMedGoogle Scholar
  191. 191.
    Cadle RM, Zenon III GJ, Rodriguez-Barradas MC, et al. Fluconazole-induced symptomatic phenytoin toxicity. Ann Pharmacother 1994; 28: 191–5PubMedGoogle Scholar
  192. 192.
    Fournier JP, Schneider S, Martinez P, et al. Hypoglycaemic coma in a patient treated with glipizide and fluconazole: a potential interaction? [in French]. Therapie 1992; 47: 446–7PubMedGoogle Scholar
  193. 193.
    Gannon RH, Anderson ML. Fluconazole-nortriptyline drug interaction. Ann Pharmacother 1992; 26: 1456–7PubMedGoogle Scholar
  194. 194.
    Konishi H, Morita K, Yamaji A. Effect of fluconazole on theophylline disposition in humans. Eur J Clin Pharmacol 1994; 46(4): 309–12PubMedCrossRefGoogle Scholar
  195. 195.
    Honig PK, Wortham DC, Zamani K, et al. The effect of fluconazole on the steady-state pharmacokinetics and electro-cardiographic pharmacodynamics of terfenadine in humans. Clin Pharmacol Ther 1993; 53: 630–6PubMedCrossRefGoogle Scholar
  196. 196.
    Anaissie E, Kontoyiannas D, Huls C, et al. Efficacy safety and pharmacokinetics of high dose fluconazole (HDFLU) in patients (pts) with fungal infections (FI) [abstract no. 626]. Abstracts of the 32nd ICAAC, 1992.Google Scholar
  197. 197.
    Fluconazole prescribing information. Pfizer Limited, Sandwich, Kent, UK, 1995.Google Scholar
  198. 198.
    Marriott DJE, Jones PD, Hoy JF, et al. Fluconazole once a week as secondary prophylaxis against oropharyngeal candidiasis in HIV-infected patients. Med J Aust 1993; 158: 312–6PubMedGoogle Scholar
  199. 199.
    Mangino JE, Moser SA, Waites K. When to use fluconazole. Lancet 1995; 345: 6–7PubMedCrossRefGoogle Scholar
  200. 200.
    Odds FC. Review: resistance of yeasts to azole-derivative antifungals. J Antimicrob Chemother 1993; 31: 463–71PubMedCrossRefGoogle Scholar
  201. 201.
    Ng TTC, Denning DW. Fluconazole resistance in Candida in patients with AIDS — a therapeutic approach. J Infect 1993; 26: 117–25PubMedCrossRefGoogle Scholar
  202. 202.
    Brown AE. Overview of fungal infections in cancer patients. Semin Oncol 1990; 17(3) Suppl. 6: 2–5Google Scholar
  203. 203.
    Wingard JR. The use of fluconazole prophylaxis in patients with chemotherapy-induced neutropenia. Leuk Lymphoma 1992; 8: 353–9PubMedCrossRefGoogle Scholar
  204. 204.
    Clumeck N. Primary prophylaxis against opportunistic infections in patients with AIDS. N Engl J Med 1995; 332(11): 739–40PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • Karen L. Goa
    • 1
  • Lee B. Barradell
    • 1
  1. 1.Adis International LimitedAuckland 10New Zealand

Personalised recommendations