578 Antifun als
Ecomi; Econitet; Ecosonet; Ecozol; Heads Shampoot; Hung. : and at least 14 days after resolution of symptoms for Gyno-Pevaryl; Pevaryl; India: Ecanol; Irl.: Ecostatint; Gyno AdverseEffects and Precautions oesophageal infections; doses of up to 400 mg daily may be Pevaryl; Israel: Gyno-Pevaryl; Pevarylt; Ita!. : Dermazolt; Eco Burning and itching have been reported after the used for oesophageal candidiasis if necessary. dergin; Ecomesol; Ecomi; Ecorex; Ecosteril; Ganazolo; Ifenec; application of fenticonazole nitrate. Fluconazole 150 mg as a single oral dose may be used for Micos; Pevaryl; Polinazolo; Malaysia: Gyno-Pevaryl; Mex.: Are Intravaginal preparations of fenticonazole may damage genital candidiasis (vaginal candidiasis or candida! colex; Micostyl; Pevaryl; Neth.: Pevaryl; Norw.: Pevaryl; NZ: latex contraceptives and additional contraceptive measures balanitis). Ecremet; Pevaryl; Philipp.: Pevaryl; Pol.: Gyno-Pevaryl; are therefore necessary during local application. Dermatophytosis, pityriasis versicolor, and Candida Pevaryl; Pevazol; Port.: Gyno-Pevaryl; Pevaryl; Rus.: Ecalin For a discussion of the caution needed when using azole infections of the skin may be treated with fluconazole (3KliJ1HH)t; Ecodax (3KOAa.Kc); Gyno-Pevaryl (fmm-IleBapHJI); antifungals during pregnancy, see under Pregnancy in lienee (HijleHex); S.Afr.: Ecodermt; Econal-Ct; Gyno-Pevaryl; 50 mg orally once daily for up to 6 weeks. Precautions of Fluconazole, p. 579.3. Pevaryl; Singapore: Gyno-Pevaryl; Pevaryl; Spain: Ecotam; Systemic candidiasis, cryptococcal meningitis, and Micoespect; Swed.: Pevaryl; Switz.: Gyno-Pevaryl; Pevaryl; other cryptococcal infections may be treated with Thai.: Econ; UK: Ecostatint; Gyno-Pevaryl; Pevaryl; Ukr.: Eco· Antimicrobial Action fluconazole orally or by intravenous infusion; the initial dax (EKOAa.Kc); USA: Ecoza; Spectazole; Venez.: Gyno-Pevaryl; dose is 400 mg followed by a maintenance dose of 200 to Fenticonazole is an imidazole antifungal active against a Miconax; Pevaryl. 400 mg once daily. Duration of therapy is based on clinical range of organisms including dermatophyte pathogens, and mycological response, but is usually at least 6 to 8 weeks Malassezia furfur, Candida a/bicans. Multi-ingredient Preparations. Arg.: Diflunazol; Filoderma Plus; and in cryptococcal meningitis; in the USA, treatment for I 0 to Griseocrem; Griseoplus; Austria: Pevisone; Belg.: Pevisonet; 12 weeks after the CSF cultures become negative is (t\:!"''T); (erffi�); China: Fu Yan Ning Ji Bai Fu Pevisone r i recommended. Fluconazole may also be used in daily doses YiFuQing Zhaohuile Pevison; P.r.�P.?. ?_! ()_n,�...... Denm.: (l!iR of I 00 to 200 mg orally or intravenously to prevent relapse Pevisonet; Fin.: Pevisone; Fr. : Pevisone; Ger.: Epipevisone; PraprielaryPreparations (details ate given in Volume B) .fil!¥tf); (:fitmil\\' ); (li!l111i'Jf); after a primary course of antifungal treatment for acute Gr.: Pevison; Hong Kong: Ecocort; Pevisone; Triamecon; Trico Single-ingredient Preparations. Austria: Lomexin; Belg.: Gynox cryptococcal meningitis in patients with AIDS. nazole; India: Bestopic; Cobederm-Ht; Ecodax-G; Halog-E; in; Braz. : Fentizol; Lomexin; Cz. : Lomexin; Fr. : Lomexin; Ter In immunocompromisedpatients at risk of fungal infections, Mediron; Israel: Pevisonet; Ital.: Pevisone; Malaysia: Aecoras; lomexin; Ger.: Fenizolan; Lomexint; Gr.: Lomexin; Hung.: fluconazole may be given prophylactically in a dose of 50 Ecocort; Econazine; Endix; Kifugan; Norw.: Pevisone; Philipp. : Gynoxin; Lomexin; Irl.: Gynoxin; Lomexin; Ital.: Falvin; to 400 mg daily orally or by intravenous infusion, although Nizolex; Pevaryl HPt; Pevisone; Pol. : Pevisone; Port.: Pevisone; Lomexin; Lore nil; Mex.: Lomexin; Neth.: Gynoxin; Pol.: S.Afr.: Pevisone; Singapore: Ecocort; Econazine; Epiderm; Pevi Gynoxin; Port.: Lomexin; Rus.: Lomexin (JloMeKCHH); S.Afr.: long-term prophylaxis has been associated with the sone; Swed.: Pevisone; Switz.: Pevisone; Thai.: Ecocort; Eco Lomexin; Spain: Laurimic; Lomexin; Turk.: Gyno-Lomexin; emergence of resistant organisms (see under Intermittent derm; Econazine; Tricozole; UK: Econacortt. (JloMeKcHH); Doses, below). UK: Gynoxin; Ukr.: Lomexin Venez.: Mycofentin. For details of doses used in children and in those with Pharmacopoeial Preparatians renal impairment, see p. 579.!. BP 2014: Econazole Cream; Econazole Pessaries. Fluconazole raAN, usAN. riNN! Reviews. 1. Grant SM, Clissold SP. Fluconazole: a review of its pharmacodynamic and pharmacok:inetic properties, and therapeutic potential in superficial and systemic mycoses. Drugs 1990; 39: 877-916. Correction. ibid. 40: 862. 2. Kowalsky SF, Dixon DM. Fluconazole: a new antifungal agent. Clin Pharm 1991; 10: 179-94. 3. Goa KL, Barradell LB . Fluconazole: an update of its pharmacodynamic and pharmacokinetic properties and therapeutic use in major superficial and systemic mycoses in immunocompromised patients. Drugs 1995; 50: 658-90. 4. Charlier C, et al. Fluconazole for the management of invasive candidiasis: where do we stand after 15 years? J Antimicrob Chemother 2006; 57: 384-410. Pharmacopoeias. In Chin., Bur. (see p. vii), and US. Pharmacopooias. In Bur. (see p. vii) for veterinary use only. Administration. HIGH DOSES. Doses higher than those in Ph. Eur. 8: (Enilconazole for Veterinary Use; Enilconazole Ph. Eur. 8: (Fluconazole). A white or almost white, licensed product information for fluconazole have been BP(Vet) 2014). A clear, yellowish, oily liquid or solid mass. hygroscopic, crystalline powder. It exhibits polymorphism. tried, and in some cases are routinely recommended, for Very slightly soluble in water; freely soluble in alcohol, in Slightly soluble in water; freely soluble in methyl alcohol; patients with some life-threatening fungal infections. For methyl alcohol, and in toluene. Store in airtight containers. soluble in acetone. Store in airtight containers. cryptococcal meningitis in HIV-infected patients, oral flu Protect from light. USP 36: (Fluconazole). A white or almost white, crystalline conazole doses of 800 mg to 2 g daily have been used in powder. Slightly soluble in water; soluble in alcohol and in some second-line induction regimens. In the USA. some acetone; sparingly soluble in chloroform and in isopropyl experts1 have suggested: Profile alcohol; freely soluble in methyl alcohol; very slightly • 800 mg daily when used with amphotericin B soluble in toluene. Store in airtight containers at a Enilconazole is an imidazole antifungal used topically in • at least 800 mg, and preferably !.2 g daily when used veterinary medicine for the treatment of fungal skin temperature below 30 degrees. with flucytosine infections in cattle, horses, and dogs. It is also used by • 800 mg to 2 g daily, preferably 1.2 g daily or more, when inhalation for the treatment of aspergillosis in ostriches. Incompatibilityand stability.References. fluconazole is used alone l. Lor E, et al. Visual compatibility of fluconazole with commonly used Daily oral doses of up to 800 mg have also been used in injectable drugs during simulated Y-site administration. Am J Hosp Pharm 1991; 48: 744-6. consolidation treatment of non-HIV infected patients with 2. Couch P, et al. Stability of fluconazole and amino adds in parenteral cryptococcal meningitis, 1 and 800 mg daily has been Fenticonazole Nitrate nutrient solutiorn. Am J Hosp Pharm 1992; 49: 1459-62. suggested for CNS blastomycosis.2 For the treatment of (BANM, USAN, rfNNM) 3. Hunt-Fugate AK, et al. Stability of fluconazole in injectable solutions. Am CNS coccidioidomycosis, some experts' suggest initial J Hosp Pharm 1993; SO: 1186-7. 4. Ishisaka DY. Visual compatibility of fluconazole with drugs given by oral doses of 800 mg to I g fluconazole daily; for continuous infusion. Am J Hosp Pharm 1994; 51: 22�0 and 2292. disseminated disease, up to 2 g daily has been used. 5. Dotson B, Churchwell MD. Physical compatibility of 4% sodium citrate Intravenous doses of 10 mg/kg daily have been tried in with 23.4% sodium chloride, fluconazole, and micafungin. Am J Health disseminated candidiasis, 4 and US guidelines' suggest up Syst Pharm 201 1; 68: 377-8. to 12 mg/kg daily if fluconazole is to be used for CNS infection. When used for treatment of disseminated Uses and Administration neonatal candidiasis, a dose of 12 mg/kg daily has also Fluconazole is a triazole antifungal used for superficial been suggested.' mucosal (oropharyngeal. oesophageal. or vaginal) candi l. Perfect JR, et al. Clinical practice guidelines for the management of diasis and for fungal skin infections. It is also given for cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2010; 50: 291-322. Also available at: http://www. systemic infections including systemic candidiasis, cocci journals.uchicago.edu/doi/pdf/ 10.1086/649858 (accessed 16/08/10) dioidomycosis, and cryptococcosis, and has been tried in 2. Chapman SW, et al. Clinical practice guidelines for the management of blastomycosis, histoplasmosis, and sporotrichosis. The place blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis 2008; 46: 1801-12. Also available at: http://www. of fluconazole in the treatment of fungal infections is journals.uchicago.edu/doi!pdf/ 10.1086/588300 (accessed 16/08/10) discussed in the various sections under Choice of Pharmacopoeias. In Bur. (see p. vil). 3. Galgiani JN, et al. Infectious Diseases Society of America. Coccidioido Antifungal, p. 563.!. Fluconazole has also been used for mycosis. Clin Infect Dis 2005; 41: 1217-23. Also available at: http://www. Ph. Eur. 8: (Fenticonazole Nitrate). A white or almost the treatment of cutaneous leishmaniasis, for details see joumals.uchicago.edu/doi/pdf/ 10.1086/496991 (accessed 16/08/10) white, crystalline powder. Practically insoluble in water; 4. Graninger W, et al. Treatment of Candida albicans fungaemia with p. 579.2. 26: sparingly soluble in dehydrated alcohol; freely soluble in fluconazole. J Infect 1993; 133-46. Fluconazole is given orally or by intravenous infusion in 5. Pappas PG, et al. Clinical practice guidelines for the management of dimethylformamide and in methyl alcohol. Protect from similar doses. For intravenous infusion it is given as a candidiasis: 2009 update by the Infectious Diseases Society of America. light. solution containing 2mg/mL at a rate of 5 to IOmL/minute Clin Infect Dis 2009; 48: 503-3 5. Also available at: http://www.journals. (300 to 600 mL/hour). In the USA. a maximum infusion uchicago.edu/doi/pdf/1 0.1086/596757 {accessed 16/08/1 0) Uses and Administration rate of 100 mL/hour is recommended. INTERMITTENT DOSES. Concern has been expressed about the For superficial mucosal candidiasis (other than increasingly widespread use of fluconazole1 and, in parti Fenticonazole is an imidazole antifungal used locally as the genital candidiasis), the usual oral dose of fluconazole in the cular, about the impact of continuous fluconazole therapy nitrate in the treatment of vulvovaginal candidiasis UK is 50 mg dally, although 100 mg daily may be given if in immunocompromised patients on the development of (p. 564.1). A 200-mg pessary is inserted into the vagina at necessary. Treatment usually continues for 7 to 14 days in resistance (see under Antimicrobial Action, p. 580.2). bedtime for 3 nights or a 600-mg pessary is inserted once oropharyngeal candidiasis (except in severely immunocom Nevertheless, fluconazole remains popular for primary and only at bedtime. It is also available as a 2% vaginal cream; promised patients), for 14 days in atrophic oral candidiasis secondary prophylaxis. Some investigators have suggested 5 g is inserted into the vagina twice daily for 3 days. associated with dentures, and for 14 to 30 days in other the use of intermittent doses2•3 although this could further Fenticonazole nitrate is also applied topically as a 2% cream mucosal candida! infections including oesophagitis. increase the risk of infections with resistant organisms. or solution for the treatment of fungal skin infections. Higher doses are recommended in the USA where an Once-weekly treatment with. fluconazole has been tried Reviews. initial dose of fluconazole 200 mg is followed by 100 mg in onychomycosis4 and tinea capitis.' In HIV-infected l. Veraldi S, Milani R. Topical fenticonazole in dermatology and once daily and where the minimum treatment period is 14 patients with oropharyngeal candidiasis, a single 750-mg gynaecology: current role in therapy. Drugs 2008; 68: 2183-94. days for oropharyngeal infection, or a minimum of 21 days oral dose of fluconazole has been reported to be as effective
All cross-references refer to entries in Volume A 579
and well tolerated as a standard, 2 week course of • patients on regular haemodialysis: 100% of the standard In one such patient, hepatotoxicity was concluded to be fluconazole 150 mg orally once daily. 6 recommended dose after each dialysis session dose-dependent -' 1. Mangino JE, et a!. When to use fluconazole. Lancet 1995; 345: 6-7. No dosage adjustment is needed in patients with renal 1. Wells C, Lever AML. Dose-dependent fluconazole hepatotoxicity proven 2. Singh N, et al. Low-dose fluconazole as primary prophylaxis for impairment given single-dose therapy. on biopsy and rechallenge. J Infect 1992; 24: 111-12. cryptocucca! infection in AIDS patients with CD4 cell counts of 2. Jacobson .MA et al. Fatal acute hepatic necrosis due to fluconazole. Am J � A review1 of antimicrobial dosing in renal replacement , J OO/mm3; demonstration of efficacy in a prospective, multicenter trial. .Med 1994; 96: 188-90. Clin Infect Dis 1996; 23: 1282-6. therapy has recommended that critically ill patients 3. Holmes J, Clements D. Jaundice in HIV positive haemophi!iac. Lancet 3. Schuman P, et al. Weekly fluconazole for the prevention of mucosal undergoing intermittent haemodialysis should receive a 1989; i: 1027. candidiasis in women with HIV infection; a randomized, double-blind, dose of 200 to 400 mg every 48 to 72 hours, or 100 to 200 mg 4. Franklin IM, et al. Fluconazole-induced jaundice. Lancet 1990; 336: 565. 126: placebo-controlled trial. Ann InternMed 1997; 689-96. every 24 hours (after dialysis on dialysis days). The authors 5. Bronstein J-A, et al. due to dose-dependent 4. Scher RK, et a!. Once-weekly fluconazole (150mg, 300 mg, or450 mg) in 1997; 25: 1266-7. the treatment of distal subungual onychomycosis of the toenail. JAm also recommend that those undergoing continuous renal Acad Dermatol 1998; 38: S77-S86. replacement therapy (CRRT) receive a loading dose of 400 Hypersensitivity. Desensitisation has been successfully car 5. Gupta AK et a!. Once weekly fluconazole is effective in children in the to 800 mg, with the following maintenance doses depending ried out in a patient with AIDS who had hypersensitivity treatment of tinea capitis: a prospective, multicentre study. Br J Dermatol on the type of CRRT: 2000; 142: 965-8. to both fluconazole and itraconazole.1 Gradually increas continuous venovenous haemofiltration (CVVH): 200 to 6. Hamza OJ, et al. Single-dose fluconazole versus standard 2-week therapy • ing oral doses of fluconazole (starting at 5 mg daily) were for oropharyngeal candidiasis in HIV-infected patients: a randomized, 400 mg every 24 hours given over 7 days; thereafter dosage was maintained at double-blind, double-dummy triaL Clin Infect Dis 2008; 47: 1270-6. continuous venovenous haemodialysis (CVVHD): 400 to • 400 mg daily. No adverse reactions were seen during 800 mg every 24 hours desensitisation or in the 3 months up to the publication of Administration in children. Fluconazole may be used in continuous venovenous haemodiafiltration (CVVHDF): • the report. neonates and children for the treatment of candidiasis and 800 mg every 24 hours 1. Takaha�hi T, et al. Desensitization to fluconazole in an AIDS patient. Ann cryp1ococcal infections (including meningitis), as well as l. Heintz BH, et al. Antimicrobial and recommendations Pharmacother 2001; 35: 642-3. for prevention of fungal infection in those who are immu renal replacement nocompromised; in children, it may also be used for the Ph,,m,,mthm•py 2009; 29: 562- treatment of fungal skin infections. Fluconazole may be i Precautions given orally, or by intravenous infusion at a rate not Leishmaniasis. Fluconazole has been tried in the treat Fluconazole should be used with caution in patients with exceeding 5 to 10 mL/min. impaired hepatic or renal function. Abnormalities in ment of cutaneous leishmaniasis (p. 922.1) caused by j For children from 4 weeks of age, the following licensed J,eishmania major. In a randomised, double-blind, placebo haematological, hepatic, and renal-function tests have been doses have been recommended, to a maximum of 400 mg 1 controlled study, 1 80 patients received a six-week course noted in patients with serious underlying diseases such as daily; the duration of treatment is generally as for adults (see of oral fluconazole 200mg daily, of whom 63 had com AIDS or malignancy. Cases of torsade de pointes and QT Uses and Administration, p. 578.2): plete healing of lesions after 3 months, compared with 22 prolongation have been reported rarely and caution is mucosal candidiasis: 3 to 6 mg/kg initially, followed by • of 65 patients who received placebo. However, others2 advised when giving fluconazole to patients with 3 mg/kg once daily have reported a response rate not significantly different proarrhythmic conditions. systemic candidiasis and cryptococcal infections: 6 • from placebo. High-dose oral fluconazole has also been Teratogenicity has occurred in animals given high doses to 12 mg/kg once daily tried for the treatment of cutaneous leishmaniasis due to of fluconazole and its use is not recommended in pregnancy prevention of fungal infections if immunocompro- • L. braziliensis. A small study3 of 28 patients reported a cure (see Pregnancy, below). mised: 3 to 12 mg/kg once daily rate of 75% for those patients who took a daily dose of Neonates may be given tbe same doses as older children, but 5 mg/kg for 4 to 12 weeks (mean 7.6 weeks) and a cure Breast feeding. Fluconazole is distributed into breast milk, the dosing interval must be extended due to slower rate of 100% for those who took a daily dose of 8 mg/kg achieving concentrations similar to those found in mater excretion of fluconazole. For neonates less than 2 weeks of for 4 to 5 weeks (mean 4.2 weeks). nal plasma, 1 and its use in women who are breast feeding age, UK licensed product information suggests doses should is not recommended by licensed product information. AA, et a!. Fluconazole for the treatment of cutaneous be given every 72 hours, for those between 2 and 4 weeks of caused by Leishmania major. N Eng! J Med 2002; 346: In one report/ no untoward effects, other than a slight age doses should be given every 48 hours. 891-5. increase in lactase dehydrogenase level, were seen in an Additionally, the BNFC makes the following unlicensed 2. Morizot G, et al. Healing of Old World cutaneous leishmaniasis in 1 infant who was exposed to fluconazole in breast milk for 6 recommendations for children from l month of age: travelers treated with l!uconazok: drug effect or weeks. evolution? Am J Trap Med Hyg 2007; 76: 48-52. Correction. treatment of tinea corporis, cruris, and pedis • 3. Sousa AQ, et al. High-dose oral fluconazole therapy elfective for The American Academy of Pediatrics considers that the infections, pityriasis versicolor, and dermal candi cutaneous leishmaniasis due to Leishmania (Vianna) braziliensis. Clin use of fluconazole is usually compatible with breast diasis: 3 mg/kg orally (maximum 50 mg) once daily for Infect Dis 201 1; 53: 693-5. feeding 3 up to 6 weeks Force RW. Fluconazole concentrations in breast milk. Pediatr Infect Di.1 J L • treatment of tinea capitis infection: 6 mg/kg orally Adverse Effects 1995; 14: 2 35-6. 2. Bodley V, Powers D. Long-term treatment of a breastfeeding mother (maximum 300 mg) once daily for 2 to 4 weeks Adverse effects reported with fluconazole most commonly prevention of relapse of cryptococcal meningitis in with fluconazole-resolved nipple pain caused by yeast: a ca�e study. J • affect the gastrointestinal tract and include abdominal pain, Hum J,act 13: 307-ll. AIDS patients after completion of primary therapy: diarrhoea, flatulence, nausea and vomiting, and taste 3. American of Pediatrics. The transfer of drugs and other 108: 6 mg/kg (maximum 200 mg) orally or intravenously disturbance. Other adverse effects include headache, chemicals into human milk. 776-89. [Retired May once daily 2010] Correction. ibid.; 1029. Also at: http://aappolicy. dizziness, leucopenia, thrombocytopenia, hyperlipidaemias, The use of fluconazole for prophylaxis in neonatal intensive aappublications.org/cgi/content/full/pediatrics%3b108/3/776 (accessed and raised liver enzyme values. Serious hepatotoxicity has 21/06/05) care has been reviewed.1-7 There is some evidence to suggest been reported in patients with severe underlying disease that prophylactic systemic fluconazole, generally for the such as AIDS or malignancy. Anaphylaxis and angioedema Porphyria. The Drug Database for Acute Porphyria, com first 4 to 6 weeks of life, may reduce the risk of invasive have been reported rarely. piled by the Norwegian Porphyria Centre (NAPOS) and fungal infections in very low birth-weight (less than Skin reactions are rare but exfoliative cutaneous the Porphyria Centre Sweden, classifies fluconazole as 1500 g) neonates.8 Doses that have been tried in some reactions such as toxic epidermal necrolysis and Stevens probably porphyrinogenic; it should be prescribed only for studies are: Johnson syndrome have occurred, more commonly in compelling reasons and precautions should be considered 3 mg/kg every third day for the first two weeks, then • patients with AIDS. in all patients. 1 every second day during the third and fourth weeks, The Drug Database for Acute Porphyria. Available at: http://www. then daily during the fifth and sixth weeks L Alopecia. Alopecia has occasionally been reported in drugs-porphyria.org (accessed 14110/11) • 3 or 6 mg/kg every second day until 30 days after birth or patients receiving fluconazole, especially during prolonged until 45 days in infants of birth-weight less than 1000 g use.L2 Pregnancy. High (toxic) doses of fluconazole, itraconazole, 6 mg/kg every third day for the first week, then every day • 1. Weinroth SE, Tuazon CU. Alopecia associated with fluconazole and ketoconazole have been reported to be teratogenic in until 4 weeks treatment. Ann InternMed 1993; 119: 637. rodents. Although there is little information about the use 2. Pappas et al. Alopecia associated with fluconazole therapy. Ann • 3 mg/kg twice weekly for six weeks of these drugs in human pregnancy, there is a report of a 1995; 123: 354-7. l. Isaacs D. Fungal prophylaxis in very low birth weight neonates: nystatin, woman who took fluconazole 400 mg daily throughout fluconazole or nothing? Curr Opin Infect Dis 2008; 21: 246-50. pregnancy and who gave birth to an infant with severe 2. Kaufman DA. Fluconazole prophylaxis: can we eliminate invasive Effect on electrolyte balance. Hypokalaemia was asso Candida intcction:. in the neonatal ICU? Curr Opin Pediatr 2008; 20: 332- ciated with fluconazole in 3 patients with acute myeloid craniofacial and limb abnormalities.1 The abnormalities 40. leukaemia. 1 resembled those associated with the Antley-Bixler 3. Healy CM, Baker CJ. Fluconazole prophylaxis in the neonatal intensive syndrome, a genetic disorder, but a teratogenic effect Kidd D, et a/. Hypokalaemia in patients with acute myeloid leukaemia care unit. Pediatr Infect Dis J 2009; 28: 49-52. L after treatment with fluconazole. Lancet 1989; 1017. could not be excluded. Although prescription-event-moni 4. Manzoni P, et al. The use of fluconazole in neonatal intensive care units. i: Arch Dis Child 2009; 94: 983-7. toring studies of fluconazole did not reveal adverse effects 5. McGuire W, Clerihew L. The effect of fluconazole prophylaxis in very Effects on the heart. Prolonged QT interval and torsade de on the fetus, 2·5 congenital abnormalities have occurred in low binhweight infants is overestimated by before-after studies. Arch Dis pointes have been reported rarely in patients receiving flu infants whose mothers were given high doses of flu con Child Fetal Neonatal Ed 2010; 95: F182-FJ87. conazole.1-5 azole for 3 months or more. In August 2011 the FDA 6. Reed BN, et a!. Fluconazole prophylaxis in high-risk neonates. Ann ! Pharmacother 2010; 44: 178-84. 1. issued a drug safety communication to draw attention to 7. Kaufman DA. Epidemiology and prevention of neonatal candidiasis: receiving fluconazole. the fact that use of long-term, high-dose fluconazole (400 fluconazole for all neonates? Adv Exp Med Biol 2010; 659: 99-119. 2. Tholakanahalli VN, et al. Fluconazole-induced torsade de pointes. Ann to 800 mg daily) during most or all of the first trimester of 8. Clerihew L, et at. Prophylactic systemic antifungal agents to prevent Pharmacother 2001; 35: 432-4. pregnancy may be associated with a rare and distinct set mortality and morbidity in very low birth weight infants. Available in 3. Kha1an M, Mathis AS. Probable case of torsades de pointes induced by The Cochrane Database of Systematic Reviews; Issue 4. Chichester: John fluconazole. 2002; 22: 1612-7. of birth defects in infants. These features include brachy Wiley; 2007 (accessed 18/01112). 4. Pham CP, et al. Long and torsade de pointes caused by cephaly, abnormal facial features and calvarial develop 40: fluconazole. Ann Pharmacother 2006; 1456-6 1. ment. cleft palate, femoral bowing, thin ribs and long 5. Administration in renal impairment. Patients with renal bones, muscle weaknesses, joint deformities, and congeni impairment may require dosage reduction. Normal loading 619-23. tal heart disease. 6 However, they also stated that a single or initial doses of oral and parenteral formulations of flu dose of fluconazole (150mg) used to treat vaginal candi conazole should be given on the first day of treatment and Effects on the liver. Although severe hepatic reactions to diasis during pregnancy does not appear to be associated subsequent doses should be adjusted according to creat fluconazole are rare they have been reported, especially in with the birth defects 6 Data collected by the manufac inine clearance (CC): patients with severe underlying diseases or hepatic dys� turer, 7 relating to 198 women exposed to itraconazole dur • CC more than 50 rnL/minute: 100% of the standard function.L2 Elevated liver enzymes are commonly found ing the first trimester of pregnancy, indicated that the mal recommended dose and there have been reports of jaundice. ?.A Hepatic necro formation rate for both exposed women and matched • CC less than 50 mL/minute and not receiving dialysis: sis has been seen rarely post mortem in patients with controls was within the expected baseline risk for the gen 50% of the standard recommended dose severe underlying disease who had received fluconazole. eral population; a prospective cohort study8 involving 206
The symbol t denotes a preparation no longer actively marketed 580 Antifun als
women with first-trimester exposure to itraconazole also episode of torsade de pointes in a patient on haemodia Pharmacokinetics found no difference in the rate of congenital abnormalities lysis.1 I between exposed and unexposed infants, although a possi l. Gandhi PJ, et al. Fluconazole- and levofloxacin-induced torsades de Fluconazole is well absorbed after oral doses, bioavailability ble increased rate of spontaneous abortion was suggested. pointes in an intensive care unit patient. Am J Health-Syst Pharm 2003; from the oral route being 90% or more of that from the Nevertheless, the manufacturers recommend that flucon 60: 2479-83. intravenous route. Mean peak plasma concentrations of azole, itraconazole, and ketoconazole should be avoided 6. 72 micrograms/mL have occurred in healthy subjects after during pregoancy. Nitrofurans. For a report of puhnonary and hepatic toxi a 400-mg oral dose. Peak concentrations occur within to 2 nitrofurantoin Licensed product information states that doses of city due to a possible interaction between hours of oral doses. Plasma concentrations are proportionalI voriconazole equivalent to those used therapeutically have and fluconazole, see p. 332.3. to the dose over a range of 50 to 400 mg. Multiple dosing been shown to be teratogenic and embryotoxic in rodents.It leads to increases in peak plasma concentrations; steady therefore recommends that voriconazole should be avoided Antimicrobial Action state concentrations are reached in 5 to 10 days but may be during pregnancy and that women of child-bearing attained on day 2 if a loading dose is given. Fluconazole is a triazole antifungal drug that in sensitive potential should use effective contraception during Fluconazole is widely distributed and the apparent fungi inhibits cytochrome P450-dependent enzymes, treatment. Similar recommendations have been made for volume of distribution is close to that of total body water. resulting in impairment of ergosterol synthesis in fungal posaconazole. Concentrations in breast milk, joint fluid, saliva, sputum, cell membranes. It is active against Blastomyces dermatitidis, Other azole antifungals including butqconazole, clotrim vaginal fluids, and peritoneal fluid are similar to those Candida spp., Coccidioides immitis, Cryptococcus neoformans, azole, econazole, miconazole, sulconazole, terconazole, achieved in plasma. Concentrations in the CSF range from Epidermophyton spp., Histoplasma capsulatum, Microsporum and tioconazole are reported to be embryotoxic but not 50 to 90% of plasma concentrations, even in the absence of spp., and Trichophyton spp. teratogenic in rodents given high doses. Many of these meningeal inflanunation. Protein binding is only about Resistance has developed in some Candida spp. following drugs are used topically or intravaginally and the systemic 12%. long-term prophylaxis with fluconazole, and cross absorption from these routes of administration varies. About 80% of a dose is excreted unchanged in the urine resistance with other azoles has been reported. While these drugs may not necessarily be contra-indicated and about 11% as metabolites. The elimination half-life of fluconazole is about 30 hours and is increased in patients in pregoancy, consideration should be given to these Microbiological interactions. A synergistic antifungal with renal impairment. Fluconazole is removed by dialysis. potential risks when choosing antifungal therapy for such effect was seen in vitro with terbinafine and fluconazole patients. against strains of Candida albicans.1 For effects on the Reviews. 1. Lee BE, et al. Congenital malformations in an infant born to a woman antifungal activity of fluconazole when given with l. Debruyne D, Ryckelynek J-P. Clinical pharmacokinetics of fluconazole. treated with fluconazole. Pediatr Infect Dis 1992; II: 1062-4. GUn Pharmacokinet 1993; 24: 10-27. J 2. Rubin PC, et al. Fluconazole and pregnancy: results of a prescription amphotericin B, see p. 572.3. 2. Debruyne D. Clinical pharmacokinetics of fluconazole in superficial and event�monitoring study. Int J Gynecol Obstet 1992; 37 (suppl): 25-7. l. Barchiesi F, et al. In vitro activities of terbinafine in combination with systemic mycoses. Clin Pharmacokinet 1997; 33: 52-77. 3. Inman W, et al. Safety of fluconazole in the treatment of vaginal fluconazole and itraconazole against isolates of Candida albicans with 3. Pittrow L, Penk A. Special pharmacokinetics of fluconazole in septic, candidiasis: a prescription-event monitoring study, with spedal reduced susceptibility to azoles. Antimicrob Agents Chemother 1997; 41: obese and bum patients. Mycoses 1999; 4l (suppl 2): 87-90. reference to the outcome of pregnancy. Bur J Clin Pharmacol l994; 46: 1812-14. 4. Silling G. Fluconazole: optimized antifungal therapy based on 115-18. pharmacokinetics. Mycoses 2002; 45 (suppl 3): 39-41. 4. S"rensen et al. Risk of malformations and other outcomes in children HI', Resistance.The emergence of strains of Candida spp. resis exposed to fluconazole in utero. Br J Clin Pharmacol 1999; 48: 234-8. Bums. The mean half-life of fluconazole was decreased to 5. N0rgaard M, et al. Maternal use of fluconazole and risk of congenital tant to fluconazole has become increasingly important, malformations: a Danish population-based cohort study. J Antimicrob particularly in immunocompromised patients receiving 24.4 hours in 9 patients with bums.1 Fluconazole clear Chmwther 2008; 62: 172-6. long-term prophylaxis with fluconazole.1·2 In addition to ance was 27.5 mL/minute, which was 30% higher than 6. FDA. FDA drug safety communication: use of long-term, high-dose resistance in C. albicans.'·' infections caused by C. dubli that reported in healthy subjects. Diflucan (fluconazole) during pregnancy may be associated with birth l. Boucher BA. et al. Fluconazole pharmacokinetics in bum patients. defects in infants (issued 3rd August, 2011). Available at: http:l/www. niensis.' C. glabrata, and krusei, all of which may be less C. Antimicrob Agents Chemother 1998; 42: 930-3. fda.gov/Drugs/DrugSafety/ucrn266030.htm (accessed 17/01112) sensitive to fluconazole than C. albicans, have been noted 7. Bar-Oz B, et al. Pregnancy outcome after in utero exposure to in these patients."· 7 and more recently the non -albicans itraconazole: a prospective cohort study. Am J Obstet Gynecol 2000; 183: species have emerged as a prontirient cause of candidiasis Children and neonates. References. 617-20. l. saxen H, et al. Pharmacokinetics of fluconazole in very low birth weight 8. De Santis M, et al. FirsHrimester itraconazole exposure and pregnancy in immunocomprontised patients. 8 Secondary resistance of infants during the first two weeks of life. Clin PharmtUOl Ther 1993; 54: outcome: a prospective cohort study of women contacting teratology C. glabrata has also been reported during fluconazole ther 269-77. information services in Italy. Drue Safety 2009; 239-44. 2. Nahata MC, Brady MT. Pharmacokinetics of fluconazole after oral 32:: apy.9·10 Resistance to fluconazole has been reported to occur more frequently than resistance to either keto con administration in children with human immunodeficiency virus infection. Bur J Clin Pharmacol 1995; 48: 291-3. Renal impairment. For dose adjustments in renal impair azole or itraconazole and may be related to the widespread use of this drug.4'7 Cross-resistance with other azolesll·12 ment, see Administration in Renal Impairment, under Distribution. Salivary concentrations of fluconazole after and with amphotericin B 13•14 has been reported. Uses and Adntinistration, p. 579.1. oral doses should be adequate for the treatment of oro Fluconazole resistance has also been reported in pharyngeal and oesophageal candidiasis1·2 even in patients Cryptococcus neoformans15 and Histoplasma capsulatum. 16 with AIDS who may have decreased salivation. 3 Treatment Histoplasmosis developed during treatment with flucon Interactions failures are more likely to be due to inadequate dosage or azole in a patient with HIV infection.l1 Fluconazole In general, fewer interactions are considered to occur with resistant organisms than to decreased salivary secretion.' resistant C. neoformans has been isolated from an fluconazole than with either itraconazole or ketoconazole. Pharmacologically active concentrations of fluconazole immunocompetent patient who had not been exposed to Use of rifampicin with fluconazole results in reduced have been detected in scalp hair' and nails5 after oral azole antifungals previously. 18 plasma concentrations of fluconazole. Use of hydrochloro treatment with conventional daily doses and with once 1. Rex JlL et al. Resistance of Candida species to fluconazole. Antimicrob weekly dosage. thiazide and fluconazole has resulted in clinically Agents Chemather 1995; 39: 1-8. insignificant increases in plasma-fluconazole concentra 2. Brion LP, et al. Risk of resistance associated with fluconazole I. Force RW, Nahata MC. Salivary concentrations of ketoconazole and tions. prophylaxis: systematic review. J Infect 2007; 54: 521-9. fluconazole: implications for drug efficacy in oropharyngeal and esophageal candidiasis. Ann Pharmacother 1995; 19: 10-15. Fluconazole may interfere with the metabolism of some 3. Sandven P, et al. Susceptibilities of Norwegian Candida albicans strains to fluconazole: emergence of resistance. Antimicrob Agents Chemother 2. Koks CHW, et al. Pharmacokinetics of fluconazole in saliva and plasma other drugs, mainly through inhibition of the cytochrome 1993; 37: 2443-8. after administration of an oral suspension and capsules. Antimicrob P450 isoenzymes CYP3A4 and CYP2C9. This may account 4. Johnson EM.. et al. Emergence of azole drug resistance in Candida species Agents Chemother 1996; 40: 1935-7. for the reported increases in plasma concentrations of b:om mv-infected patients receiving prolonged fluconazole therapy for 3. Garda-Hennoso D, et al. Fluconazole concentrations in saliva from AIDS oral candidosis. J Antimicrob Chemother 1995; 35: 103-14. patients with oropharyngeal candidosis refractory to treatment with bosentan, ciclosporin, midazolam, nevirapine, amitripty 39: 5. Ruhnke M, etal. Development of simultaneous resistance to fluconazole fluconazole. Antimicrob Agents Chemother 1995; 656-60. line, nortriptyline, phenytoin, rifabutin, sulfonylurea in Candida albicans and Candida dubliniensis in a patient with AIDS. J 4. Yeates R.. et al. Accumulation of fluconazole in scalp hair. J Clin hypoglycaentics and nateglinide, selective cyclo-oxyge Antimicrob Chemother 2000; 46: 291-5. Pharmaco/ 1998; 38: 138-43. nase-2-inhibitors such as celecoxib and parecoxib, 6. Price et al. Fluconazole susceptibilities of Candida species and 5. Faergemann J. Pharmacokinetics of fluconazole in skin and nails. JAm MF, Acad Dennatol 1999; (suppl): S14-S20. tacrolimus, triazolam, warfarin, and zidovudine; flucon distribution of species recovered from blood cultures over a 5-year 40 period. Antimicrob Agents Chemother 1994; 38: 1422-4. azole may inhibit the formation of a toxic metabolite of 7. Odds FC. Resistance of yeasts to azole-derivative antifungals. J HIV·infected patients. Plasma clearance of fluconazole sulfamethoxazole. Antimicrob Chemother 1993; 31: 463-71. may be lower in patients with HIV infection than in Increases in terfenadine concentrations after high doses 8. Kanafani ZA, Perfect JR. Resistance to antifungal agents: mechanisms immunocompetent patients, and the half-life may be pro of fluconazole have been associated with ECG abnormal and clinical impact. Clin Infect Dis 2008; 46: 120-8. 9. Hitchcock CA, et al. Fluconazole resistance in Candida glabrata. longed.1·2 ities. A similar effect may be anticipated with astemizole. Antimicrob Agents Chemother 1993; 37: 1962-5. 1 . Tett S, et al. Pharmacokinetics and bioavailability of fluconazole in two Use of fluconazole with cisapride could result in increased 10. Miyazaki H, et al. Fluconazole resistance associated with drug efflux and groups of males with human immunodeficiency virus infection cisapride concentrations and associated toxicity. The use of increased transcription of a drug transporter gene, PDH1, in Candida (IllY) compared with those in a group of males without mv infection. fluconazole with astemizole, cisapride, or terfenadine glabrata. Antimicrob Agents Chemother 1998; 42: 1695-1701. Antimicrob Agents Chemother 1995; 39: 1835-41. 11. Martinez-Suarez JV, Rodriguez-Tudela JL. Patterns of in vitro activity of should therefore be avoided because of the risk of cardiac 2. McLachlan AJ,Tett SE. Pharmacokinetics of fluconazole in people with itraconazole and imidazole antifungal agents against Candida albicans HIV infection: a population analysis. Br J Clin Pharmaco/ 1996; 41: 291-8. arrhythmias. Syncope attributed to increased amitriptyline with decreased susceptibility to fluconazole from Spain. Antimicrob concentrations has occurred when antitriptyline was given Agents Chemother 1995; 39: 1512-16. 12. Goldman M, et al. Does long-term itraronazole prophylaxis result in in with fluconazole. P..r�P.�.��-��� ...... Fluconazole may also reduce the clearance of theo vitro azole resistance in mucosal Candida albicans isolates from persons with advanced human immunodeficiency virus infection? Antimicrob Proprietary Preparations (details are given in Volume B) phylline. The concentration of contraceptive steroids has Agents Chemother 2000; 44: 1585-7. been reported to be both increased and decreased in patients 13. Kelly SL, et al. Resistance to fluconazole and amphotericin in Candida Single-ingredient Preparations. Arg.: Antimicon; Candinticol; receiving fluconazole and the efficacy of oral contraceptives albicans b:om AIDS patients. Lancet 1996; 348: 1523-4. Damicol; Femixol; Flucoginkan; Flucolaf; Fluconovag; Fluzol; 14. Nolte FS, et al. Isolation and characterization of fluconazole- and Fungicil; Fungocina; Fungototal; Honguil Plus; Klonarizol; Klo may be affected. amphotericin B-resistant Candida albicans b:om blood of two patients nazolt; Micolis Novo; Micoral Fluco; Mutum; Naxo C; Nifurtox; For further information on interactions between drugs with leukemia. Antimicrob Agents Chemother 1997; 41: 196-9. Nimic; Niofen; Periplum; Ponaris; Proseda F; Triflucan; Aus metabolised by the cytochrome P450 isoenzyme CYP3A and 15. Venkateswarlu K, et al. Fluconazole tolerance in clinical isolates of tral.: Canesoral; Di-Con One; Diflucan; Dizole; Flufeme; Flu azoles, see under Itraconazole, p. 585.1. Cryptococcus neoform.ans. Antimicrob AgentsChemother 1997; 41: 748- 51. zole; Ozole; Austria: Diflucan; Difluzol; Flucosept; Fungata; 16. Wheat J, et al. Hypothesis on the mechanism of resistance to fluconazole Belg.: Candizole; Diflucan; Fungimed; Braz.: Candixt; Candi Antineoplastics. For the effect of azole antifungals on in Histoplasma capsulatum. Antimicrob Agents Chemother 1997; 41: 410- zol; Floltec; Flucanil; Flucazol; Flucocin; Flucodan; Flucol; Flu cyclophosphamide:metabolism, see p. 773.3. 14. corned; Fluconal; Fluconeo; Fluconid; Flucoton; Flucozen; Flu 17. Pottage JC, Sha BE. Development of histoplasmosis via human san; Fluxilase; Fungnon; Glyflucan; Helmicin; Pantec; immunodeficiency virus infected patient receiving fluconazole. J Infect Riconazol; Triazol; Unizol; Zelix; Zolanixt; Zolmic; Zoltec; Zolt Dis 1991; 164: 622-3. Fluoraquinolones. Both levofloxacin and fluconazole can 18. Omi-Wasserlauf R.. et al. Fluconazole-resistant Cryptococcus neofor ren; Canad.: Diflucan; Chile: Diflucan; Felcar; Felsol; Flucoxan; cause a prolonged QT interval. The simultaneous use of mans isolated from an immunocompetent patient without prior Fluctin; Fungimax; Ibarin; Microvacdn; Plusgin; Tavor; China: intravenous levofloxacin and fluconazole resulted in an exposure to fluconazole. Clin Infect Dis 1999; 29: 1592-3. Bin li (it<}J); Conquer Diflucan Fu Da (fii!;:); (j:J:t!l); (t#Ci!;:); All cross-references refer to entries in Volume A Fu Kang Fupengxing Hao Kang (""}ji); Hong 5-ffuorocytoslRe; headache, sedation, and vertigo, and also allergic reactions, (Jf'Jr); (if±JfJ(); 2(1 Xu Guang(J'I;:J\:); Hu Qi (:liti't!ll.Hua); Shi Xin Jin 4"�mino-5:t1uorooyrlmidin- h)-one, toxic epidermal necrolysis, and cardiotoxicity. Alterations in Zhou Kai Xing Kang Li Yin (}ji:fl:t';l); Ke Da (iJLM:l't); C'ASc.H.FN ,Qb129c.1 liver function tests are generally dose-related and reversible; Kang (Jit)liJ); Lai Kang (i!ill�); Li Xing Luo Rui hepatotoxicity may also occur. Hypokalaemia may occur. Medoflucon Mei Di Ke Qian De 0-.21DOJ1i£J'2!},85-7.2J ; )02/>.XOl. (flf:itmt); (3itm); (i:IJ!l.); (!J¥Jilij); "- There have been a few reports of peripheral neuropathy. QianYi Qu Er Man Duo (i!li!J;§>l't);Ru Ning (ii>:'T); Sai ATG (3\'il!li\mt); (§ii[JXSl); dfl!!l); QDOiAE2J; Bone-marrow depression, especially leucopenia and Ke Lu Ding(\!!:J!'i); (:ti'"Ji!i\T ); Shuai Ke Feng (i�5'/:JX\); Shuang Wei ATC Vet.-:-Df)32B2DTo6 QJ02AXO l: Du Qing Sunvecon Tai Ning Wei UNit -"' thrombocytopenia, is associated with blood concentrations Pharmacopoeias. In Chin., Eur. (see p. vii), Int., Jpn, and US. of flu cytosine greater than 100 micrograms/mL, with Ke Hen (x)()!l(:}!l!Ff);Wen Qing Ctil'i);(::C:i{iU.:li); Xinlizuo ({i'f:f0($T);1l'i'); Yi Li Kang (\k:f0J$t);(iifiTOO);Yi Qi Fu Yi Zhen Shi You Ni Ph. Eur. 8: (Flucytosine). A white or almost white concurrent use of amphotericin B, and with renal An Cz. ; Diflazont;('"lkli!d; Diflucan; Flucot;(Jia Forcan;oll!i!l); Myco crystalline powder. Sparingly soluhle in water; slightly impairment. Fatal agranulocytosis and aplastic anaemia max;(Jt!B't); Mycosyst; Mykohexal; Denm.: Diflucan; Fluconastad; soluble in dehydrated alcohol. Protect from light. have been reported. Generazolet; Lozanoc; Stadanazol; Fin.: Canesoral; Diflucan; USP 36: (Flucytosine). A white to off-white crystalline Fr. : Beagyne; Triflucan; Ger.: Canifug Flucot; Diflucan; Fluco Effects on the blood. Bone marrow toxicity associated powder, odourless or with a slight odour. Sparingly soluble beta; Flucoderm; FlucoLich; Flunazul; Fungata; Gr.: Azoflu; with flucytosine has been attributed to its conversion to in water; slightly soluble in alcohol; practically insoluble in Azzol-S; Dalrich; Diflucan; Falipan; Farviron; Figalol; Flucalit; fluorouracil, possibly by intestinal flora.1 A pilot study2 of chloroform and in ether. Store in airtight containers. Protect Flucanid; Flucocaps; Flucodrug; Flucofin; Fluconapen; Flucor 6 patients given intravenous flucytosine found that the from light. an; Flucovein; Flucozol; Flukatril; Flusenil; Fluzomic; Fumecal; amounts of fluorouracil in serum samples were undetect Funadel; Fungo; Fungram; Fungustatin; Fungusteril; Fuxilidin; able, whereas flucytosine could be detected in the samples. Gynosant; Hadlinol; Medoflucon; Mycazole; Neomycolt; Novo Stability. A solution of flucytosine for intravenous infusion This might be because intravenous dosage did not allow flon; Opumyk; Rifagen; Stabilanol; Tierlite; Varmec; Zidonil; should be stored between 18 degrees and 25 degrees. Pre the conversion of flucytosine to fluorouracil by intestinal Hong Kong: Diflazon; Diflucan; Flucoric; Flucozal; Fludicon; cipitation may occur at lower temperatures and decompo microflora. However, one patient still developed thrombo Forcant; Lucan; Nofung; Stalene; Vick-Flucan; Hung.: Dermyc; sition, with the formation of fluorouracil, at higher tem cytopenia and another leucocytopenia and the authors Diflucan; Flucohexal; Fluconer; Flucorict; Mycosyst; Nofung; peratures. India: Adcon; Adecon; AF; Aglucon; Alfa Tab; Alfucoz; Alicon; hypothesised that toxicity might be due to flucytosine and Alsflu; Antican-0; Aviflu; Cancap; Candicon; Cinflu; Clozole; not the metabolite. Concize; Conflu; Cyflu; E-Flu; Endida; Excan; F-Con; F-Zole; Uses and Administration 1. Pirmohamed M, et al. The role of active metabolites in drug toxicity. Drug 1994; 11: 114-44. Fabizol; Fantizole; Fasicon: FCN; Fiscon; Fixit; Flecon; Flori; Flucytosine is a fluorinated pyrimidine antifungal used in Flozol; Fluact; Flubit; Flue; Flucalup; Flucan; Flucare; Flucoat; 2. A, et al. 5-fluorocytosine-related bone-marrow dcprc5sion and the treatment of systemic fungal infections, the treatments conversion to fluorouracil: a pilot study. Fundam Clin Pharmacal 2002; Flucolab; Flucomet; Flucoric; Flucos; Flucoside; Flucovar; Flu for which are discussed under Choice of Antifungal, 16: 39--47. cozed; Fludia; Flufact; Flufung; Fluka; Flukamep; Plumed; Flu 1 , p. 563.1. It is mainly used with amphotericin B or micon; Flunaz; Flunec; Flunif; Flunova; Fluol; Flusta; Flustate; fluconazole in the treatment of severe systemic candidiasis Flusyst; Flutaur; Flutel; Flutrox; Fluzart; Fluzeet; Fluzide; Flu Precautions zole; Fluzon; Foflu; Forcan; Ful; Fumac; Fumycin; Funcan; and cryptococcal meningitis. It has also been tried in other Flucytosine should be given with great care to patients with Funesta; Fungal-F; Fungard; Fungazol; Fungdor; Fungiban; infections due to susceptible fnngi including chromoblas renal impairment, or with blood disorders or bone marrow Fungicon; Fungid; Fungina; Fungisan-F; Fungo; Funspor; tomycosis. depression. Renal and hepatic function and blood counts Fusys; Futiza; GFlu; Glenflu; Gocan; Gusnil; Hif; Indcon; Kair Flucytosine is given by intravenous infusion as a 1 flu; Kit; Kon; Koni; Kozole; Leecon; Lido; Logican; Lozic; solution over 20 to 40 minutes. The usnal dose is 200 mg/kgI% should be monitored during therapy (at least weekly in Lucoz; M-Fluk; Myconorm-F; Mycorest; Mycosure; Myzole; daily in 4 divided doses; a dose of 00 to 150 mg/kg daily patients with renal impairment or blood disorders). In NBOzole; Neocon; Nipcan; Nuforce; Odicon; One Can; Optican; may be sufficient in some patients.I Dosage should be patients with renal impairment, doses should be reduced Ozus; Syscan; Indon.: Cancidt; Candipar; Candizolt; Cryptal; adjusted to produce trough plasma concentrations of 2 5 to and trough blood concentrations of flucytosine should be Diflucan; Flucesst; Flucoral; Fludis; Funzela; Govazol; Kifluzol; 50 micrograms/rnL.This is particularly important in patients checked regularly from blood samples taken just before an Zemyc; Irl.: ByFluc; CanOral; Diflazole; Di±lucan; Flucandidt; with AIDS who are at increased risk of bone marrow injection of flucytosine (see under Uses, above). Care should Flucol; Israel: Diflucan; Flucanol; Stabilanol; Trican; Triflucan; toxicity. Parenteral treatment is rarely given for more than 7 be taken in patients given radiation therapy or other drugs Ital.: Alozof; Aviflucox; Canazol; Diflucan; Dizolo; Elazor; Flu days, except for cryptococcal meningitis when it is 1 which depress bone marrow. kimex; Flumicon; Flumos; Fluores; Fungus; Klaider; Lefunzol; continued for at least 4 months. For intravenous doses to Flucytosine is teratogenic in rats. Miconix; Riflax; Trirnikos; Winch; Zerfun; Zoloder; Jpn: be used in patients with renal impairment. see below. Diflucan; Malaysia: Avezol; Biozole; Diflucan; Difluvid; Flucess; AIDS. Frequent bone marrow toxicity has been reported Flucon; Fluconol; Flucoric; Flugal; Fukole; Medoflucon; Odaft; Flucytosine is given orally in usual doses of 50 to in patients with AJDS during flucytosine therapy.' How Stalene; Zolstan; Mex. : Afungil; Bioxel; Candizol; Diflucan; 150 mg/kg daily in 4 divided doses. Again, blood ever, in a study in 381 patients, no additional haemato Difusel; Fectrin; Fharder; Fleridux; Flucoxan; Fludisol; Fluhex concentrations should be monitored and dosage adjusted alt; Flukezol; Fluxes; Fluxicap; Fluzort: Fucandyl; Funser; Lan in patients with renal impairment to avoid accumulation of toxicity was reported in patients given amphotericin B fluzol; Menifar; Neofomiral; Ongicil; Oxifungol; Ranflut: Solar the drug. plus flucytosine compared with those given amphotericin isolt; Terplex; Trifuncan; Zilrin; Zoldicam; Neth.: Diflucan; For details of doses in children, see below. B alone.2 The toxicity could be minimised by monitoring Flucodermt; Norw.: Diflucan; NZ: Canesten Fluconazole; Flucytosine has been used topically for azole-refractory serum concentrations3 and the British Society for Antimi Diflucan; Flucasten; Flucazole; Philipp.: Diflucan; Dyzolor; vaginitis caused by Candida spp., but such use may increase crobial Chemotherapy has suggested that these should be Exomax; Flucandia; Flucon; Flucoral; Fluzocan; Fukole; Funze problems of resistance. maintained within 25 to 50micrograms/mL in patients la; Odaft; Reflucan; Syscan; Pol.: Diflucan; Flucofast; Fluco with AIDS 4 Reviews. LEKt; Fluconazin; Flucona; Flumycon; Mycomax; Mycosyst; I. Chuck SL, Sande Infections with neoformans in the I. Viviani Flucytosine-what is its future? J Antimicrob Chemother . Azoflunet; Diflucan; Fludocel; Maxflint; Reforce; Supre . acquired immunodeficiencyMA syndrome. 1989; 321: 794-9. Port.: 1995; 35:MA241-4. 2. van der Horst CM, et a!. Treatment of cryptococcal meningitis associated mase; Rus.: Diflazon (.Umfma3oH); Diflucan ()ln¢moKaH); Fluco 2. Summers KK, et al. Therapeutic drug monitoring of systemic antifungal with the acquired immunodeficiency syndrome. N Eng! J Med 1997; 337: mabol (nyKoMa6on); Flucostat (nroKOCTaT); Flucozan therapy. J Antimicrob Chemother 1997; 40: 753-64. 1' 15-21. (.rry:Ko3aH); Flucozyd (