      Document 0242
 DOCN  DRG0242
 UNIQUE IDENTIFIER        DRG-0005
 NAME OF SUBSTANCE        Fluconazole [USAN 1995]
 REGISTRY NUMBER          86386-73-4
 STANDARD CHEMICAL NAME   1H-1,2,4-Triazole-1-ethanol,
                          alpha(2,4-difluorophenyl)-
                          alpha-(1H-1,2,4-triazol-1-ylmethyl)- [USAN
                          1995]
 SYNONYMS                 Diflucan [USAN 1995]
 SYNONYMS                 Triflucan [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 026
 PROTOCOL ID NUMBERS      NIAID ACTG 059
 PROTOCOL ID NUMBERS      FDA 012A
 PROTOCOL ID NUMBERS      FDA 012B
 PROTOCOL ID NUMBERS      FDA 012C
 PROTOCOL ID NUMBERS      FDA 012D
 PROTOCOL ID NUMBERS      FDA 012E
 PROTOCOL ID NUMBERS      FDA 012G
 PROTOCOL ID NUMBERS      FDA 012H
 PROTOCOL ID NUMBERS      FDA 012I
 PROTOCOL ID NUMBERS      FDA 012J
 PROTOCOL ID NUMBERS      FDA 012K
 PROTOCOL ID NUMBERS      FDA 012L
 PROTOCOL ID NUMBERS      FDA 012M
 PROTOCOL ID NUMBERS      FDA 012P
 PROTOCOL ID NUMBERS      NIAID CPCRA 010
 PROTOCOL ID NUMBERS      FDA 012Q
 PROTOCOL ID NUMBERS      FDA 012R
 PROTOCOL ID NUMBERS      FDA 120
 PROTOCOL ID NUMBERS      FDA 213A
 PROTOCOL ID NUMBERS      FDA 226A
 PROTOCOL ID NUMBERS      FDA 236A
 PROTOCOL ID NUMBERS      FDA 012F
 PROTOCOL ID NUMBERS      FDA 012N
 PROTOCOL ID NUMBERS      NIAID ACTG 159
 PROTOCOL ID NUMBERS      NIAID ACTG 174
 PROTOCOL ID NUMBERS      NIAID ACTG 202
 PROTOCOL ID NUMBERS      NIAID ACTG 981
 PROTOCOL ID NUMBERS      NIAID CPCRA 030
 PROTOCOL ID NUMBERS      NIAID 95 CC-102
 PROTOCOL ID NUMBERS      NIAID ACTG 283
 SECONDARY SOURCE ID      UK-49,858 [USAN 1995]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Rapidly absorbed in humans
                          (peak plasma levels occur between 1.0 and 2.0
                          hours, with plasma half-life of 25 hours);
                          well distributed in all tissues; easily
                          crosses blood-cerebrospinal fluid barrier;
                          eliminated largely unchanged in urine (about
                          80 percent); low level of hepatic metabolism;
                          may affect drug-metabolizing enzymes. A
                          highly selective inhibitor of fungal
                          cytochrome P-450 sterol C-14 alpha
                          demethylation. Mammalian cell demethylation
                          is much less sensitive to fluconazole
                          inhibition. The subsequent loss of normal
                          sterols correlates with accumulation of 14
                          alpha methyl sterols in fungi and may be
                          responsible for the fungistatic activity of
                          fluconazole. [PDR 1995]
 DISEASES STUDIED/TREATED FDA approved 1/29/90 for the treatment of
                          cryptococcal meningitis and oropharyngeal and
                          esophageal candidiasis. [PDR 1995]
 CLASSIFICATION CODE      Antifungal [USAN 1995]
 OTHER MAJOR USES         Treatment of serious systemic candidal
                          infections, including urinary tract
                          infection, peritonitis, and pneumonia [PDR
                          1995]
 SUBSTANCE INTERACTIONS   Significantly prolongs Pentobarbitone
                          sleeping time (animal studies). Increased
                          prothrombin time after warfarin
                          administration. Clinically or potentially
                          significant interactions between fluconazole
                          and the following drugs/classes have been
                          reported: oral hypoglycemics, coumarin type
                          anticoagulants, phenytoin, cyclosporine,
                          rifampin and theophyline. Concurrent use with
                          terfenadine should be closely monitored since
                          serious cardiac dysrhythmias have been
                          observed with other azole antifungals. [PDR
                          1995; NIAID ACTG 059]
 ADVERSE EFFECTS          May cause mild to moderate nausea, headache,
                          and abdominal pain; may cause subdued
                          behavior, decreased activity and respiration
                          and ataxia, prostration, blanching,
                          hypothermia, and labored respiration at high
                          doses. Hepatotoxicity, anaphylaxis, seizures,
                          exfoliative skin disorders, leukopenia and
                          thrombocytopenia, hypercholesterolemia,
                          hypertriglyceridemia and hypokelemic adverse
                          events have also occurred. [PDR 1995; NIAID
                          ACTG 059]
 CONTRAINDICATIONS        Should not be used by patients with a history
                          of allergy or intolerance to imidazoles,
                          azoles, or Amphotericin B.  [NIAID ACTG 059]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Broad spectrum bis-triazole
                          antifungal agent [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C13H2F2N6O [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 306.28 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White crystalline solid
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 138-140 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C50.98%, H3.95%,
                          F12.41%, N27.44%, O5.22% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Slightly soluble in water and
                          saline [PDR 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: After reconstitution the
                          suspensions retain their potency for 14 days.
                          [USP DI 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets (50, 100, and 200 mg);
                          oral suspension (35 ml bottles containing 10
                          or 40 mg/ml); intravenous solutions, 2
                          mg/ml). [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral; intravenous
                          injection. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store tablets below 30C; store
                          unreconstituted suspension powder below 30C
                          and reconstituted suspension between 30C and
                          5C. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store injections between 25C and 5C
                          (brief exposure up to 40C does not adversely
                          affect drug. [PDR 1995]
 MANUFACTURERS            Pfizer
 REFERENCES               Laine L, Rabeneck L. Prospective study of
                          fluconazole suspension for the treatment of
                          oesophageal candidiasis in patients with
                          AIDS. Aliment Pharmacol Ther. 1995
                          Oct;9(5):553-6.
 REFERENCES               Flynn PM, Cunningham CK, Kerkering T, San
                          Jorge AR, Peters VB, Pitel PA, Harris J,
                          Gilbert G, Castagnaro L, Robinson P.
                          Oropharyngeal candidiasis in
                          immunocompromised children: a randomized,
                          multicenter study of orally administered
                          fluconazole suspension versus nystatin. The
                          Multicenter Fluconazole Study Group. J
                          Pediatr. 1995 Aug;127(2):322-8.
 REFERENCES               Barbaro G, Barbarini G, Di Lorenzo G.
                          Fluconazole vs. flucytosine in the treatment
                          of esophageal candidiasis in AIDS patients; a
                          double-blind, placebo-controlled study.
                          Endoscopy. 1995 Jun;27(5):377-83.
 REFERENCES               Bruzzese VL, Gillum JG, Israel DS, Johnson
                          GL, Kaplowitz LG, Polk RE. Effect of
                          fluconazole on pharmacokinetics of
                          2',3'-dideoxyinosine in persons seropositive
                          for human immunodeficiency virus. Antimicrob
                          Agents Chemother. 1995 May;39(5):1050-3.
 REFERENCES               Barbaro G, Di Lorenzo G. Comparison of
                          therapeutic activity of fluconazole and
                          itraconazole in the treatment of oesophageal
                          candidiasis in AIDS patients: a double-blind,
                          randomized, controlled clinical study. Ital J
                          Gastroenterol. 1995 May;27(4):175-80.
 REFERENCES               Garcia-Hermoso D, Dromer F, Improvisi L,
                          Provost F, Dupont B. Fluconazole
                          concentrations in saliva from AIDS patients
                          with oropharyngeal candidosis refractory to
                          treatment with fluconazole. Antimicrob Agents
                          Chemother. 1995 Mar;39(3):656-60.
 REFERENCES               Powderly WG, Finkelstein D, Feinberg J, Frame
                          P, He W, van der Horst C, Koletar SL, Eyster
                          ME, Carey J, Waskin H, et al. A randomized
                          trial comparing fluconazole with clotrimazole
                          troches for the prevention of fungal
                          infections in patients with advanced human
                          immunodeficiency virus infection. NIAID AIDS
                          Clinical Trials Group [see comments]. N Engl
                          J Med. 1995 Mar 16;332(11):700-5.
 REFERENCES               Diz Dios PD, Alvarez Alvarez J, Fernandez
                          Feijoo J, Castro Ferreiro M. Fluconazole
                          response patterns in HIV-infected patients
                          with oropharyngeal candidiasis. Oral Surg
                          Oral Med Oral Pathol Oral Radiol Endod. 1995
                          Feb;79(2):170-4.
 REFERENCES               de Lalla F, Pellizzer G, Vaglia A, Manfrin V,
                          Franzetti M, Fabris P, Stecca C. Amphotericin
                          B as primary therapy for cryptococcosis in
                          patients with AIDS:reliability of relatively
                          high doses administered over a relatively
                          short period. Clin Infect Dis. 1995
                          Feb;20(2):263-6.
 REFERENCES               Johnson EM, Warnock DW, Luker J, Porter SR,
                          Scully C. Emergence of azole drug resistance
                          in Candida species from HIV-infected patients
                          receiving prolonged fluconazole therapy for
                          oral candidosis. J Antimicrob Chemother. 1995
                          Jan;35(1):103-14.
 ENTRY MONTH              8906
 LAST REVISION DATE       960424
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
