BNF for Children 2011-2012

BNFC 2011–2012 8.2.2 Corticosteroids and other immunosuppressants 433Prophylaxis of acute rejection in hepatictransplantation in combination with a corticosteroidand ciclosporin or tacrolimus. By mouthConsult local treatment protocol for detailsChild 1 month–18 years 10 mg/kg twice daily,increased to 20 mg/kg twice daily (max. 2 g daily)Note Tablets and capsules not appropriate for dose titrationin children with body surface area less than 1.25 m 2Mycophenolate Mofetil (Non-proprietary) ACapsules, mycophenolate mofetil 250 mg, net price100-cap pack = £35.00Tablets, mycophenolate mofetil 500 mg, net price 50-tab pack = £31.50Brands include Arzip cCellCept c (Roche) ACapsules, blue/brown, mycophenolate mofetil250 mg, net price 100-cap pack = £82.26Tablets, lavender, mycophenolate mofetil 500 mg, netprice 50-tab pack = £82.26Oral suspension, mycophenolate mofetil 1 g/5 mLwhen reconstituted with water, net price 175 mL =£115.16Excipients include aspartame (section 9.4.1)8.2.2 Corticosteroids and otherimmunosuppressantsThe corticosteroids prednisolone and dexamethasoneare widely used in paediatric oncology; they have amarked antitumour effect. Dexamethasone is preferredfor acute lymphoblastic leukaemia whilst prednisolonemay be used for Hodgkin’s disease, non-Hodgkin’slymphoma, and B-cell lymphoma and leukaemia.Dexamethasone is the corticosteroid of choice in paediatricsupportive and palliative care. For children whoare not receiving a corticosteroid as a component oftheir chemotherapy, dexamethasone may be used toreduce raised intracranial pressure (see p. 19), or tohelp control emesis when combined with an appropriateanti-emetic (see p. 19). For more information on glucocorticoidtherapy, including the disadvantages of treatment,see section 6.3.2.The corticosteroids are also powerful immunosuppressants.They are used to prevent organ transplant rejection,and in high dose to treat rejection episodes.Ciclosporin (cyclosporin), a calcineurin inhibitor, is apotent immunosuppressant which is virtually non-myelotoxicbut markedly nephrotoxic. It may be used inorgan and tissue transplantation, for prevention of graftrejection following bone marrow, kidney, liver, pancreas,heart, lung, and heart-lung transplantation, and forprophylaxis and treatment of graft-versus-host disease.Ciclosporin also has a role in steroid-sensitive and steroid-resistantnephrotic syndrome; in corticosteroid-sensitivenephrotic syndrome it may be given with prednisolone(section 6.3).Tacrolimus is also a calcineurin inhibitor. Although notchemically related to ciclosporin it has a similar mode ofaction and side-effects.Sirolimus is a non-calcineurin inhibiting immunosuppressant.Basiliximab is a monoclonal antibody that prevents T-lymphocyte proliferation; it is used for prophylaxis ofacute rejection in allogeneic renal transplantation. It isgiven with ciclosporin and corticosteroid immunosuppressionregimens; its use should be confined to specialistcentres.Antithymocyte immunoglobulin (rabbit) is used forthe prophylaxis of organ rejection in renal and heartallograft recipients and for the treatment of corticosteroid-resistantallograft rejection in renal transplantation.Tolerability is increased by pretreatment with anintravenous corticosteroid and antihistamine; an antipyreticdrug such as paracetamol may also be beneficial.NICE guidanceImmunosuppressive therapy for renaltransplantation in children and adolescents(April 2006)NICE has recommended that for induction therapyin the prophylaxis of organ rejection, either basiliximabor daclizumab [discontinued] are options forcombining with a calcineurin inhibitor. For eachindividual, ciclosporin or tacrolimus is chosen asthe calcineurin inhibitor on the basis of side-effects.Mycophenolate mofetil is recommended as part ofan immunosuppressive regimen only if:. the calcineurin inhibitor is not tolerated, particularlyif nephrotoxicity endangers the transplantedkidney; or. there is very high risk of nephrotoxicity from thecalcineurin inhibitor, requiring a reduction in thedose of the calcineurin inhibitor or its avoidance.Mycophenolic acid is not recommended as part ofan immunosuppressive regimen for renal transplantationin children or adolescents.Sirolimus [not licensed for use in children] is recommendedas a component of immunosuppressiveregimen only if intolerance necessitates the withdrawalof a calcineurin inhibitor.These recommendations may not be consistent withthe marketing authorisation of some of the products.ANTITHYMOCYTEIMMUNOGLOBULIN (RABBIT)Cautions see notes above; monitor blood countContra-indications infectionPregnancy manufacturer advises use only if potentialbenefit outweighs risk—no information availableBreast-feeding manufacturer advises avoid—noinformation availableSide-effects nausea, vomiting, dysphagia, diarrhoea;hypotension; infusion-related reactions (includingcytokine release syndrome and anaphylaxis, see notesabove), serum sickness; fever, shivering, increasedsusceptibility to infection; increased susceptibility tomalignancy; lymphopenia, neutropenia, thrombocytopenia;myalgia; pruritus, rash8 Malignant disease and immunosuppression