BNF for Children 2011-2012

BNFC 2011–2012 9.8.1 Drugs used in metabolic disorders 491Miglustat, an inhibitor of glucosylceramide synthase, islicensed in adults for the treatment of mild to moderatetype I Gaucher’s disease in patients for whom imigluceraseis unsuitable; it is given by mouth.IMIGLUCERASECautions monitor for imiglucerase antibodies; whenstabilised, monitor all parameters and response totreatment at intervals of 6–12 monthsPregnancy manufacturer advises use with caution—limited information availableBreast-feeding no information availableSide-effects hypersensitivity reactions (includingurticaria, angioedema, cyanosis, hypotension, flushing,tachycardia, paraesthesia, backache); less commonlynausea, vomiting, diarrhoea, abdominalcramps, fatigue, headache, dizziness, fever, arthralgia,injection-site reactionsIndication and doseGaucher’s disease type I (specialist use only). By intravenous infusionNeonate initially 60 units/kg once every 2 weeks,adjusted according to response; doses as low as30 units/kg once every 2 weeks may be appropriateChild 1 month–18 years initially 60 units/kgonce every 2 weeks, adjusted according toresponse; doses as low as 30 units/kg once every 2weeks may be appropriateGaucher’s disease type III (specialist use only). By intravenous infusionNeonate 60–120 units/kg once every 2 weeks,adjusted according to responseChild 1 month–18 years 60–120 units/kg onceevery 2 weeks, adjusted according to responseAdministration For intravenous infusion, initiallyreconstitute with Water for Injections (200 units in5.1 mL, 400 units in 10.2 mL) to a concentration of40 units/mL; dilute requisite dose with SodiumChloride 0.9% to a final volume of 100–200 mL; giveinitial dose at a rate not exceeding 0.5 units/kg/minute, subsequent doses to be given at a rate notexceeding 1 unit/kg/minute; administer within 3hours of reconstitutionCerezyme c (Genzyme) AIntravenous infusion, powder for reconstitution,imiglucerase, net price 200-unit vial = £535.65; 400-unit vial = £1071.29Electrolytes Na + 0.62 mmol/200-unit vial, 1.24 mmol/400-unit vialVELAGLUCERASE ALFACautions monitor immunoglobulin G (IgG) antibodyconcentration in severe infusion-related reactions or ifthere is a lack or loss of effect with velaglucerase alfaInfusion-related reactions Infusion-related reactions verycommon; manage by slowing the infusion rate, or interruptingthe infusion, or minimise by pre-treatment with anantihistamine, antipyretic, or corticosteroid—consult productliteraturePregnancy manufacturer advises use with caution—limited information availableBreast-feeding manufacturer advises use with caution—noinformation availableSide-effects nausea, abdominal pain, tachycardia,hypertension, hypotension, flushing, headache, dizziness,malaise, pyrexia, arthralgia, bone pain, backpain, hypersensitivity reactions, rash, urticariaIndication and doseGaucher’s disease type I (specialist use only). By intravenous infusionChild 4–18 years 60 units/kg once every 2weeks; adjusted according to response to 15–60 units/kg once every 2 weeksAdministration for intravenous infusion, reconstituteeach 400-unit vial with 4.3 mL water for injections;dilute requisite dose in 100 mL Sodium Chloride 0.9%and give over 60 minutes through a 0.22 micron filter;start infusion within 24 hours of reconstitutionVPRIV c (Shire HGT) TAIntravenous infusion, powder for reconstitution,velaglucerase alfa, net price 400-unit vial = £1410.20Electrolytes Na + 0.53 mmol/400-unit vialMucopolysaccharidosisLaronidase, an enzyme produced by recombinant DNAtechnology, is licensed for long-term replacement therapyin the treatment of non-neurological manifestationsof mucopolysaccharidosis I, a lysosomal storage disordercaused by deficiency of alpha-L-iduronidase.Idursulfase, an enzyme produced by recombinant DNAtechnology, is licensed for long-term replacement therapyin mucopolysaccharidosis II (Hunter syndrome), alysosomal storage disorder caused by deficiency ofiduronate-2-sulfatase.Galsulfase, a recombinant form of human N-acetylgalactosamine-4-sulfatase,is licensed for long-term replacementtherapy in mucopolysaccharidosis VI (Maroteaux-Lamysyndrome).Infusion-related reactions Infusion-related reactionsoften occur with administration of laronidase,idursulfase, and galsulfase; they can be managed byslowing the infusion rate or interrupting the infusion,and can be minimised by pre-treatment with an antihistamineand an antipyretic. Recurrent infusion-relatedreactions may require pre-treatment with a corticosteroid—consultproduct literature for details.GALSULFASECautions respiratory disease; acute febrile or respiratoryillness (consider delaying treatment)Infusion-related reactions See notes abovePregnancy manufacturer advises avoid unless essentialBreast-feeding manufacturer advises avoid—noinformation availableSide-effects abdominal pain, umbilical hernia, gastroenteritis;chest pain, hypertension; dyspnoea,apnoea, nasal congestion; rigors, malaise, areflexia;pharyngitis; conjunctivitis, corneal opacity; ear pain;facial oedema9 Nutrition and blood