BNF for Children 2011-2012

490 9.8.1 Drugs used in metabolic disorders BNFC 2011–20129 Nutrition and bloodLicensed use not licensed for use by intravenousinfusion; tablets, chewable tablets, and oral liquid(10%) not licensed in children under 12 years;paediatric oral solution (30%) not licensed in childrenover 12 years; not licensed for use in organicacidaemiasIndication and dosePrimary deficiency and organic acidaemias. By mouthNeonate 50 mg/kg twice daily, higher doses up to200 mg/kg daily occasionally requiredChild 1 month–18 years 50 mg/kg twice daily,higher doses up to 200 mg/kg daily occasionallyrequired; usual max. 3 g daily. By intravenous infusionNeonate initially 100 mg/kg over 30 minutes followedby a continuous infusion of 4 mg/kg/hourChild 1 month–18 years initially 100 mg/kg over30 minutes followed by a continuous infusion of4 mg/kg/hour. By slow intravenous injection over 2–3 minutesNeonate up to 100 mg/kg/daily in 2–4 divideddosesChild 1 month–18 years up to 100 mg/kg/dailyin 2–4 divided dosesSecondary deficiency in dialysis patients. By slow intravenous injection over 2–3 minutesChild 1 month–18 years 20 mg/kg after eachdialysis session, adjusted according to plasmacarnitineconcentration. By mouth(maintenance therapy if benefit gained from firstintravenous course)Child 1 month–18 years 1 g dailyAdministration for intravenous infusion, dilute injectionwith Sodium Chloride 0.9% or Glucose 5% or 10%.Carnitor c (Sigma-Tau) ATablets, L-carnitine 330 mg, net price 90-tab pack =£103.95Chewable tablets, L-carnitine 1 g, net price 10-tabpack = £35.00Oral liquid, L-carnitine 100 mg/mL (10%), net price10 10-mL (1-g) single-dose bottle = £35.00Paediatric oral solution, L-carnitine 300 mg/mL(30%), net price 20 mL = £21.00Injection, L-carnitine 200 mg/mL, net price 5-mLamp = £11.90Fabry’s diseaseAgalsidase alfa and agalsidase beta, enzymes producedby recombinant DNA technology, are licensedfor long-term enzyme replacement therapy in Fabry’sdisease (a lysosomal storage disorder caused by deficiencyof alpha-galactosidase A).AGALSIDASE ALFA and BETACautions interactions: Appendix 1 (agalsidase alfaand beta)Infusion-related reactions Infusion-related reactions verycommon; manage by slowing the infusion rate or interruptingthe infusion, or minimise by pre-treatment with an antihistamine,antipyretic, or corticosteroid—consult productliteraturePregnancy use with cautionBreast-feeding use with caution—no informationavailableSide-effects gastro-intestinal disturbances, taste disturbances;tachycardia, bradycardia, palpitation,hypertension, hypotension, chest pain, oedema,flushing; dyspnoea, cough, rhinorrhoea; headache,fatigue, dizziness, asthenia, paraesthesia, syncope,neuropathic pain, tremor, sleep disturbances; influenza-likesymptoms, nasopharyngitis; muscle spasms,myalgia, arthralgia; eye irritation; tinnitus; hypersensitivityreactions, angioedema, pruritus, urticaria,rash, acne; less commonly cold extremities, parosmia,ear pain and swelling, skin discoloration, and injection-sitereactionsIndication and doseFabry’s disease (specialist use only)see under preparationsFabrazyme c (Genzyme) AIntravenous infusion, powder for reconstitution,agalsidase beta, net price 5-mg vial = £315.08; 35-mgvial = £2196.59DoseFabry’s disease (specialist use only). By intravenous infusionChild 8–18 years 1 mg/kg every 2 weeksAdministration for intravenous infusion, reconstitute initiallywith Water for Injections (5 mg in 1.1 mL, 35 mg in 7.2 mL) toproduce a solution containing 5 mg/mL; dilute with SodiumChloride 0.9% (for doses less than 35 mg dilute with at least50 mL; doses 35–70 mg dilute with at least 100 mL; doses 70–100 mg dilute with at least 250 mL; doses greater than 100 mgdilute with 500 mL) and give through an in-line low proteinbinding0.2 micron filter at an initial rate of no more than 15 mg/hour; for subsequent infusions, infusion rate may be increasedgradually once tolerance has been establishedReplagal c (Shire HGT) AConcentrate for intravenous infusion, agalsidasealfa 1 mg/mL, net price 1-mL vial = £356.85; 3.5-mLvial = £1068.64DoseFabry’s disease (specialist use only). By intravenous infusionChild 7–18 years 200 micrograms/kg every 2 weeksAdministration for intravenous infusion, dilute requisite dosewith 100 mL Sodium Chloride 0.9% and give over 40 minutesusing an in-line filter; use within 3 hours of dilutionGaucher’s diseaseImiglucerase, an enzyme produced by recombinantDNA technology, is administered as enzyme replacementtherapy in Gaucher’s disease, a familial disorderaffecting principally the liver, spleen, bone marrow, andlymph nodes.Velaglucerase alfa, an enzyme produced by recombinantDNA technology, is administered as enzyme replacementtherapy for the treatment of type I Gaucher’sdisease.