BNF for Children 2011-2012

306 5.2.4 Echinocandin antifungals BNFC 2011–20125 Infectionscontrol reactions); avoid rapid infusion (risk of arrhythmias);interactions: Appendix 1 (amphotericin)Anaphylaxis Anaphylaxis occurs rarely with any intravenousamphotericin product and a test dose is advisablebefore the first infusion in children over 1 month of age; thepatient should be carefully observed for at least 30 minutesafter the test dose. Prophylactic antipyretics or hydrocortisoneshould only be used in patients who have previouslyexperienced acute adverse reactions (in whom continuedtreatment with amphotericin is essential)Renal impairment use only if no alternative; nephrotoxicitymay be reduced with use of lipid formulationPregnancy not known to be harmful, but manufacturersadvise avoid unless potential benefit outweighsriskBreast-feeding no information availableSide-effects when given parenterally, anorexia,nausea and vomiting, diarrhoea, epigastric pain; febrilereactions, headache, muscle and joint pain;anaemia; disturbances in renal function (includinghypokalaemia and hypomagnesaemia) and renaltoxicity; also cardiovascular toxicity (includingarrhythmias, blood pressure changes), blood disorders,neurological disorders (including hearing loss,diplopia, convulsions, peripheral neuropathy,encephalopathy), abnormal liver function (discontinuetreatment), rash, anaphylactoid reactions (seeAnaphylaxis, above); pain and thrombophlebitis atinjection siteLicensed use intravenous conventional formulationamphotericin (Fungizone c ) is licensed for use inchildren (age range not specified by manufacturer);Ambisome c not licensed for use in children under 1monthIndication and doseSystemic fungal infections. By intravenous infusionSee preparationsNote Different preparations of intravenous amphotericinvary in their pharmacodynamics, pharmacokinetics,dosage, and administration; these preparations shouldnot be considered interchangeable. To avoid confusion,prescribers should specify the brand to be dispensed.Fungizone c (Squibb) AIntravenous infusion, powder for reconstitution,amphotericin (as sodium deoxycholate complex), netprice 50-mg vial = £3.88Electrolytes Na + < 0.5 mmol/vialDoseSystemic fungal infection. By intravenous infusionNeonate 1 mg/kg once daily, increased if necessary to1.5 mg/kg daily; after 7 days, may be reduced to 1–1.5 mg/kg on alternate daysChild 1 month–18 years initial test dose of 100 micrograms/kg(max. 1 mg) included as part of first dose of250 micrograms/kg daily; increased over 2–4 days, iftolerated, to 1 mg/kg daily; in severe infection max.1.5 mg/kg daily or on alternate daysNote prolonged treatment usually necessary; if interruptedfor longer than 7 days, recommence at250 micrograms/kg daily and increase graduallyAdministration For intravenous infusion, reconstitute each vialwith 10 mL Water for Injections and shake immediately to producea 5 mg/mL colloidal solution; dilute further in Glucose 5% toa concentration of 100 micrograms/mL (in fluid-restricted children,up to 400 micrograms/mL given via a central line); pH ofglucose solution must not be below 4.2 (check each container—consult product literature for details of buffer); infuse over 4–6hours, or if tolerated over a minimum of 2 hours (initial test dosegiven over 20–30 minutes); begin infusion immediately afterdilution and protect from light; incompatible with Sodium Chloridesolutions—flush existing intravenous line with Glucose 5% oruse separate line; an in-line filter (pore size no less than 1 micron)may be usedLipid formulationsAbelcet c (Cephalon) AIntravenous infusion, amphotericin 5 mg/mL as lipidcomplex with L-a-dimyristoylphosphatidylcholine andL-a-dimyristoylphosphatidylglycerol, net price 20-mLvial = £77.43 (hosp. only)Electrolytes Na + 3.12 mmol/vialDoseSevere invasive candidiasis; severe systemic fungalinfections in children not responding to conventionalamphotericin or to other antifungal drugs or wheretoxicity or renal impairment precludes conventionalamphotericin, including invasive aspergillosis,cryptococcal meningitis and disseminated cryptococcosisin children with HIV. By intravenous infusionChild 1 month–18 years initial test dose of 100 micrograms/kg(max. 1 mg) then 5 mg/kg once dailyAdministration for intravenous infusion, allow suspension toreach room temperature, shake gently to ensure no yellow settlement,withdraw requisite dose (using 17–19 gauge needle) intoone or more 20-mL syringes; replace needle on syringe with a 5-micron filter needle provided (fresh needle for each syringe) anddilute in Glucose 5% to a concentration of 2 mg/mL; preferablygive via an infusion pump at a rate of 2.5 mg/kg/hour (initial testdose given over 15 minutes); an in-line filter (pore size no less than15 micron) may be used; do not use sodium chloride or otherelectrolyte solutions—flush existing intravenous line with Glucose5% or use separate lineAmBisome c (Gilead) AIntravenous infusion, powder for reconstitution,amphotericin 50 mg encapsulated in liposomes, netprice 50-mg vial = £96.69Electrolytes Na + < 0.5 mmol/vialExcipients include sucrose 900 mg/vialDoseSevere systemic or deep mycoses where toxicity(particularly nephrotoxicity) precludes use of conventionalamphotericin; suspected or proven infectionin febrile neutropenic patients unresponsive tobroad-spectrum antibacterials. By intravenous infusionNeonate 1 mg/kg once daily; increased if necessary to3 mg/kg once daily; max. 5 mg/kg once dailyChild 1 month–18 years initial test dose 100 micrograms/kg(max. 1 mg) then 3 mg/kg once daily; max.5 mg/kg once dailyVisceral leishmaniasis see section 5.4.5 and productliteratureAdministration for intravenous infusion, reconstitute each vialwith 12 mL Water for Injections and shake vigorously to produce apreparation containing 4 mg/mL; withdraw requisite dose fromvial and introduce into Glucose 5% or 10% through the 5-micronfilter provided, to produce a final concentration of 0.2 –2 mg/mL;infuse over 30–60 minutes, or if non-anaphylactic infusion-relatedreactions occur infuse over 2 hours (initial test dose given over 10minutes); an in-line filter (pore size no less than 1 micron) may beused; incompatible with sodium chloride solutions—flush existingintravenous line with Glucose 5% or 10%, or use separate line5.2.4 Echinocandin antifungalsThe echinocandin antifungals include caspofungin andmicafungin. They are only active against Aspergillusspp. and Candida spp; however micafungin is not usedfor the treatment of aspergillosis. Echinocandins are not