BNF for Children 2011-2012

BNFC 2011–2012 5.2.1 Triazole antifungals 301conazole (section 5.2.1) is an alternative for Candidaalbicans infection in clinically stable children who havenot received an azole antifungal recently. Amphotericinshould be considered for the initial treatment of CNScandidiasis. Voriconazole (section 5.2.1) can be usedfor infections caused by fluconazole-resistant Candidaspp. when oral therapy is required, or in children intolerantof amphotericin or an echinocandin. In refractorycases, flucytosine (section 5.2.5) can be used withintravenous amphotericin.Cryptococcosis Cryptococcosis is uncommon butinfection in the immunocompromised, especially HIVpositivechildren, can be life-threatening; cryptococcalmeningitis is the most common form of fungal meningitis.The treatment of choice in cryptococcal meningitisis amphotericin (section 5.2.3) by intravenous infusionwith flucytosine (section 5.2.5) by intravenous infusionfor 2 weeks, followed by fluconazole (section 5.2.1) bymouth for 8 weeks or until cultures are negative. Incryptococcosis, fluconazole is sometimes given alone asan alternative in HIV-positive children with mild localisedinfection or in those who cannot tolerate amphotericin.Following successful treatment, fluconazole canbe used for prophylaxis against relapse until immunityrecovers.Histoplasmosis Histoplasmosis is rare in temperateclimates; it can be life-threatening, particularly in HIVinfectedchildren. Itraconazole (section 5.2.1) can beused for the treatment of immunocompetent childrenwith indolent non-meningeal infection, includingchronic pulmonary histoplasmosis. Amphotericin (section5.2.3) by intravenous infusion is preferred in childrenwith fulminant or severe infections. Followingsuccessful treatment, itraconazole can be used forprophylaxis against relapse until immunity recovers.Skin and nail infections Mild localised fungal infectionsof the skin (including tinea corporis, tinea cruris,and tinea pedis) respond to topical therapy (section13.10.2). Systemic therapy is appropriate if topical therapyfails, if many areas are affected, or if the site ofinfection is difficult to treat such as in infections of thenails (onychomycosis) and of the scalp (tinea capitis).Oral imidazole or triazole antifungals (particularly itraconazole)and terbinafine are used more frequentlythan griseofulvin because they have a broader spectrumof activity and require a shorter duration of treatment.Tinea capitis is treated systemically; additional topicalapplication of an antifungal (section 13.10.2) mayreduce transmission. Griseofulvin (section 5.2.5) isused for tinea capitis; it is effective against infectionscaused by Trichophyton tonsurans and Microsporumspp. Terbinafine (section 5.2.5) is used for tinea capitiscaused by T. tonsurans [unlicensed indication]; the roleof terbinafine in the management of Microsporum infectionsis uncertain. Fluconazole (section 5.2.1) or itraconazole(section 5.2.1) are alternatives in the treatmentof tinea capitis caused by T. tonsurans orMicrosporum spp. [both unlicensed indications].Pityriasis versicolor (section 13.10.2) may be treatedwith itraconazole (section 5.2.1) by mouth if topicaltherapy is ineffective; fluconazole (section 5.2.1) bymouth is an alternative. Oral terbinafine is not effectivefor pityriasis versicolor.Antifungal treatment may not be necessary in asymptomaticchildren with tinea infection of the nails. If treatmentis necessary, a systemic antifungal is more effectivethan topical therapy. Terbinafine (section 5.2.5) anditraconazole (section 5.2.1) have largely replacedgriseofulvin for the systemic treatment of onychomycosis,particularly of the toenail; they should beused under specialist advice. Although terbinafine isnot licensed for use in children, it is considered to bethe drug of choice for onychomycosis. Itraconazole canbe administered as intermittent ‘pulse’ therapy. For therole of topical antifungals in the treatment of onychomycosis,see section 13.10.2.Immunocompromised children Immunocompromisedchildren are at particular risk of fungal infectionsand may receive antifungal drugs prophylactically; oraltriazole antifungals are the drugs of choice for prophylaxis.Fluconazole (section 5.2.1) is more reliablyabsorbed than itraconazole (section 5.2.1), but fluconazoleis not effective against Aspergillus spp. Itraconazoleis preferred in patients at risk of invasive aspergillosis.Micafungin (section 5.2.4) can be used forprophylaxis of candidiasis in patients undergoing haematopoieticstem cell transplantation when fluconazoleor itraconazole cannot be used.Amphotericin (section 5.2.3) by intravenous infusion orcaspofungin (section 5.2.4) is used for the empiricaltreatment of serious fungal infections in immunocompromisedchildren; caspofungin is not effective againstfungal infections of the CNS.5.2.1 Triazole antifungalsFor the role of triazole antifungal drugs in the preventionand systemic treatment of fungal infections, see p. 300.Fluconazole is very well absorbed after oral administration.It also achieves good penetration into the cerebrospinalfluid to treat fungal meningitis. Fluconazole isexcreted largely unchanged in the urine and can be usedto treat candiduria.Itraconazole is active against a wide range of dermatophytes.There is limited information available on usein children. Itraconazole capsules require an acid environmentin the stomach for optimal absorption.Itraconazole has been associated with liver damage andshould be avoided or used with caution in children withliver disease; fluconazole is less frequently associatedwith hepatotoxicity.Voriconazole is a broad-spectrum antifungal drugwhich is licensed in adults for the treatment of lifethreateninginfections.FLUCONAZOLECautions concomitant use with hepatotoxic drugs,monitor liver function with high doses or extendedcourses—discontinue if signs or symptoms of hepaticdisease (risk of hepatic necrosis); susceptibility to QTinterval prolongation; interactions: Appendix 1(antifungals, triazole)Contra-indications acute porphyria (section 9.8.2)Hepatic impairment toxicity with related drugsRenal impairment usual initial dose then halve subsequentdoses if estimated glomerular filtration rateless than 50 mL/minute/1.73m 25 Infections