BNF for Children 2011-2012

438 8.2.3 Rituximab and alemtuzumab BNFC 2011–2012Prophylaxis of graft rejection following heart transplantationfollowing antibody induction, startingwithin 5 days of transplantation. By mouthNeonate initially 50–150 micrograms/kg twice daily,adjusted according to whole-blood concentrationChild 1 month–18 years initially 50–150 micrograms/kg twice daily, adjusted according to whole-blood concentrationAllograft rejection resistant to conventional immunosuppressivetherapy Consult local treatment protocolModified releaseAdvagraf c is not licensed for use in childrenAdvagraf c (Astellas) ACapsules, m/r, tacrolimus (as monohydrate)500 micrograms (yellow/orange), net price 50-cappack = £35.79; 1 mg (white/orange), 50-cap pack =£71.59, 100-cap pack = £143.17; 3 mg (red/orange),50-cap pack = £214.76; 5 mg (red/orange), 50-cappack = £266.92. Label: 23, 25, counselling, skilledtasksExtemporaneous formulations available seeExtemporaneous Preparations, p. 68 Malignant disease and immunosuppressionVivadex c (Dexcel) ACapsules, tacrolimus 500 micrograms (ivory), netprice 50-cap pack = £46.41; 1 mg (white), 50-cap pack= £60.21, 100-cap pack = £120.41; 5 mg (red), 50-cappack = £222.44. Label: 23, counselling, skilled tasksDoseProphylaxis of graft rejection following liver transplantation,starting 12 hours after transplantation. By mouthNeonate initially 150 micrograms/kg twice daily,adjusted according to whole-blood concentrationChild 1 month–18 years initially 150 micrograms/kgtwice daily, adjusted according to whole-blood concentrationProphylaxis of graft rejection following kidneytransplantation, starting within 24 hours of transplantation. By mouthNeonate initially 150 micrograms/kg twice daily,adjusted according to whole-blood concentrationChild 1 month–18 years initially 150 micrograms/kgtwice daily, adjusted according to whole-blood concentrationNote A lower initial dose of 100 micrograms/kg twicedaily has been used in adolescents to prevent very high‘trough’ concentrationsProphylaxis of graft rejection following heart transplantationwithout antibody induction, starting within12 hours of transplantation. By mouthNeonate initially 150 micrograms/kg twice daily as soonas clinically possible (8–12 hours after discontinuation ofintravenous infusion), adjusted according to whole-bloodconcentrationChild 1 month–18 years initially 150 micrograms/kgtwice daily as soon as clinically possible (8–12 hours afterdiscontinuation of intravenous infusion), adjustedaccording to whole-blood concentrationProphylaxis of graft rejection following heart transplantationfollowing antibody induction, startingwithin 5 days of transplantation. By mouthNeonate initially 50–150 micrograms/kg twice daily,adjusted according to whole-blood concentrationChild 1 month–18 years initially 50–150 micrograms/kg twice daily, adjusted according to whole-blood concentrationAllograft rejection resistant to conventional immunosuppressivetherapy Consult local treatment protocol8.2.3 Rituximab andalemtuzumabRituximab, a monoclonal antibody which causes lysisof B lymphocytes, has been used as a component of thetreatment of post-transplantation lymphoproliferativedisease, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma,and severe cases of resistant immune modulateddisease including idiopathic thrombocytopenia purpura,haemolytic anaemia, and systemic lupus erythematosus.Full resuscitation facilities should be at hand and aswith other cytotoxics, treatment should be undertakenunder the close supervision of a specialist.Rituximab should be used with caution in childrenreceiving cardiotoxic chemotherapy or with a historyof cardiovascular disease; in adults exacerbation ofangina, arrhythmia, and heart failure have beenreported. Transient hypotension occurs frequently duringinfusion and antihypertensives may need to bewithheld for 12 hours before infusion. Progressive multifocalleucoencephalopathy (which is usually fatal orcauses severe disability) has been reported in associationwith rituximab; children treated with rituximabshould be monitored for cognitive, neurological, orpsychiatric signs and symptoms. If progressive multifocalleucoencephalopathy is suspected, suspend treatmentuntil it has been excluded.Infusion-related side-effects (including cytokine releasesyndrome) are reported commonly with rituximab andoccur predominantly during the first infusion; theyinclude fever and chills, nausea and vomiting, allergicreactions (such as rash, pruritus, angioedema, bronchospasmand dyspnoea), flushing and tumour pain. Childrenshould be given paracetamol and an antihistaminebefore each dose of rituximab to reduce these effects.Premedication with a corticosteroid should also beconsidered. The infusion may have to be stopped temporarilyand the infusion-related effects treated—consultproduct literature or local treatment protocol forappropriate management. Evidence of pulmonary infiltrationand features of tumour lysis syndrome should besought if infusion-related effects occur.Fatalities following severe cytokine release syndrome(characterised by severe dyspnoea) and associated withfeatures of tumour lysis syndrome have occurred 1–2hours after infusion of rituximab. Children with a hightumour burden as well as those with pulmonary insufficiencyor infiltration are at increased risk and should bemonitored very closely (and a slower rate of infusionconsidered).