BNF for Children 2011-2012

BNFC 2011–2012 8.1.3 Antimetabolites 423Epirubicin hydrochloride (Non-proprietary) AInjection, epirubicin hydrochloride 2 mg/mL, netprice 5-mL vial = £18.31, 25-mL vial = £92.13, 50-mLvial = £95.54, 100-mL vial = £306.20Injection, powder for reconstitution, epirubicinhydrochloride, net price 50-mg vial = £91.54Pharmorubicin c Solution for Injection (Pharmacia)AInjection, epirubicin hydrochloride 2 mg/mL, netprice 5-mL vial = £19.31, 25-mL vial = £96.54, 100-mLvial = £386.16MITOXANTRONE(Mitozantrone)Cautions see section 8.1 and notes aboveHepatic impairment use with caution—consult localtreatment protocolPregnancy avoid; effective contraception during andfor at least 6 months after treatment in men orwomen; see also Pregnancy and Reproductive Function,p. 416Breast-feeding discontinue breast-feedingSide-effects see section 8.1 and notes above; transientblue-green discoloration of urine; less commonlygastro-intestinal bleeding, anorexia, allergic reactions,dyspnoea, fatigue, fever, amenorrhoea, and transientblue discoloration of skin and nailsLicensed use not licensed for use in childrenIndication and doseAcute myeloid leukaemia, recurrent acutelymphoblastic leukaemia. By intravenous infusionConsult local treatment protocol for detailsMitoxantrone (Non-proprietary) AConcentrate for intravenous infusion, mitoxantrone(as hydrochloride) 2 mg/mL, net price 10-mL vial =£100.00Onkotrone c (Baxter) AConcentrate for intravenous infusion, mitoxantrone(as hydrochloride) 2 mg/mL, net price 10-mL vial =£121.85, 12.5-mL vial = £152.33, 15-mL vial = £203.048.1.3 AntimetabolitesAntimetabolites are incorporated into new nuclearmaterial or they combine irreversibly with cellularenzymes and prevent normal cellular division.Cytarabine, fludarabine, mercaptopurine, methotrexate,and tioguanine are commonly used in paediatricchemotherapy.Methotrexate inhibits the enzyme dihydrofolate reductase,essential for the synthesis of purines and pyrimidines.It is given by mouth, intravenously, intramuscularly,or intrathecally. Methotrexate causesmyelosuppression, mucositis, and rarely pneumonitis.It is contra-indicated in significant renal impairmentbecause it is excreted primarily by the kidney. It is alsocontra-indicated in patients with severe hepatic impairment.It should also be avoided in the presence ofsignificant pleural effusion or ascites because it canaccumulate in these fluids, and its subsequent returnto the circulation may cause myelosuppression. Systemictoxicity may follow intrathecal administrationand blood counts should be carefully monitored. Folinicacid (section 8.1) following methotrexate administrationhelps to prevent methotrexate-induced mucositis andmyelosuppression.Cytarabine acts by interfering with pyrimidine synthesis.It is given subcutaneously, intravenously, orintrathecally. It is a potent myelosuppressant andrequires careful haematological monitoring. A liposomalformulation of cytarabine for intrathecal use is availablefor lymphomatous meningitis.Fludarabine is generally well tolerated but does causemyelosuppression, which may be cumulative.Fludarabine has a potent and prolonged immunosuppressiveeffect. Children treated with fludarabineare more prone to serious bacterial, opportunisticfungal, and viral infections, and prophylactic therapyis recommended in children at risk. To preventpotentially fatal transfusion-related graft-versushostreaction, only irradiated blood products shouldbe administered. Prescribers should consult specialistliterature when using highly immunosuppressivedrugs.Clofarabine is licensed for the treatment of acutelymphoblastic leukaemia in children who have relapsedor are refractory after receiving at least two previousregimens. It is given by intravenous infusion.Nelarabine is licensed for the treatment of T-cell acutelymphoblastic leukaemia and T-cell lymphoblasticlymphoma in children who have relapsed or who arerefractory after receiving at least two previous regimens.It is given by intravenous infusion. Neurotoxicityis common with nelarabine, and close monitoring forneurological events is strongly recommended—discontinuetreatment if neurotoxicity occurs.Mercaptopurine is used as maintenance therapy foracute lymphoblastic leukaemia and in the managementof ulcerative colitis and Crohn’s disease (section 1.5).Azathioprine, which is metabolised to mercaptopurine,is generally used as an immunosuppressant (section8.2.1 and section 10.1.3). The dose of both drugs shouldbe reduced if the child is receiving allopurinol since itinterferes with their metabolism. For the role of thiopurinemethyltransferase (TPMT) in the metabolism ofazathioprine see section 8.2.1.Tioguanine (thioguanine) is given by mouth for thetreatment of acute lymphoblastic leukaemia; it is givenat various stages of treatment in short-term cycles.Tioguanine has a lower incidence of gastro-intestinalside-effects than mercaptopurine. Long-term therapywith tioguanine is no longer recommended because ofthe high risk of liver toxicity.CLOFARABINECautions see section 8.1; cardiac diseaseHepatic impairment manufacturer advises caution inmild to moderate impairment; avoid in severeimpairmentRenal impairment manufacturer advises caution inmild to moderate impairment; avoid in severeimpairmentPregnancy manufacturer advises avoid (teratogenic inanimal studies); see also Pregnancy and ReproductiveFunction, p. 416Breast-feeding discontinue breast-feeding8 Malignant disease and immunosuppression