BNF for Children 2011-2012

BNFC 2011–2012 8.1 Cytotoxic drugs 417Dexrazoxane, an iron chelator, is licensed in adults forthe prevention of chronic cumulative cardiotoxicitycaused by doxorubicin or epirubicin treatment inadvanced or metastatic cancer patients who have previouslyreceived anthracycline therapy. In practice, dexrazoxaneis used for any patient receiving anthracyclinetherapy with evidence of subclinical cardiotoxicitythought to be secondary to anthracycline therapy, orfor those children at risk of anthracycline-induced cardiotoxicity.Children receiving dexrazoxane should continueto be monitored for cardiac toxicity. The myelosuppresiveeffects of dexrazoxane may be additive tothose of chemotherapy.DEXRAZOXANECautions see notes above; monitor full blood countHepatic impairment monitor liver functionRenal impairment use with caution—risk of accumulation;manufacturer of Cardioxane c advisesreduce dose by 50% if creatinine clearance less than40 mL/minute/1.73 m 2Pregnancy avoid unless essential (toxicity in animalstudies); ensure effective contraception during and for3 months after treatment in men and womenBreast-feeding discontinue breast-feedingSide-effects nausea, vomiting, dyspepsia, abdominalpain, diarrhoea, stomatitis, dry mouth, anorexia;dyspnoea; dizziness, syncope, asthenia, paraesthesia,tremor, fatigue, drowsiness; pyrexia; vaginalhaemorrhage; myalgia; blood disorders (includinganaemia, leucopenia, neutropenia, and thrombocytopenia);alopecia, pruritus; peripheral oedema, injection-sitereactions including phlebitis; also reportedsecondary malignanciesIndication and dosePrevention of anthracycline-induced cardiotoxicity(see notes above). By intravenous infusion, 30 minutes prior toanthracycline administration10–20 times the doxorubicin-equivalent dose(depending on treatment protocol) or 10 times theepirubicin-equivalent doseAdministration for intravenous infusion reconstituteeach vial with 25 mL Water for Injections then dilutecontents of each vial with 25–100 mL CompoundSodium Lactate; give over 15 minutesCardioxane c (Novartis) TAIntravenous infusion, powder for reconstitution,dexrazoxane (as hydrochloride), net price 500-mg vial= £156.57HyperuricaemiaHyperuricaemia, which may be present in high-gradelymphoma and leukaemia, can be markedly worsenedby chemotherapy and is associated with acute renalfailure.Allopurinol is used routinely in children at low tomoderate risk of hyperuricaemia. It should be started24 hours before treatment; patients should be adequatelyhydrated (consideration should be given toomitting phosphate and potassium from hydrationfluids). The dose of mercaptopurine or azathioprineshould be reduced if allopurinol is given concomitantly(see Appendix 1).Rasburicase is a recombinant urate oxidase used inchildren who are at high-risk of developing hyperuricaemia.It rapidly reduces plasma uric acid and may be ofparticular value in preventing complications followingtreatment of leukaemias or bulky lymphomas.ALLOPURINOLCautions ensure adequate fluid intake; for hyperuricaemiaassociated with cancer therapy, allopurinoltreatment should be started before cancer therapy;interactions: Appendix 1 (allopurinol)Hepatic impairment reduce dose, monitor hepaticfunctionRenal impairment manufacturer advises reduce doseor increase dose interval in severe impairment; adjustdose to maintain plasma-oxipurinol concentrationbelow 100 micromol/litrePregnancy toxicity not reported; manufactureradvises use only if no safer alternative and diseasecarries risk for mother or childBreast-feeding present in milk—not known to beharmfulSide-effects rashes (withdraw therapy; if rash mildre-introduce cautiously but discontinue immediatelyif recurrence—hypersensitivity reactions occur rarelyand include exfoliation, fever, lymphadenopathy,arthralgia, and eosinophilia resembling Stevens-Johnson or toxic epidermal necrolysis, vasculitis,hepatitis, renal impairment, and very rarely seizures);gastro-intestinal disorders; rarely malaise, headache,vertigo, drowsiness, visual and taste disturbances,hypertension, alopecia, hepatotoxicity, paraesthesiaand neuropathy, blood disorders (including leucopenia,thrombocytopenia, haemolytic anaemia andaplastic anaemia)Indication and doseProphylaxis of hyperuricaemia associated withcancer chemotherapy, prophylaxis of hyperuricaemicnephropathy, enzyme disorders causingincreased serum urate e.g. Lesch-Nyhansyndrome. By mouthChild 1 month–15 years 10–20 mg/kg daily(max. 400 mg daily), preferably after foodChild 15–18 years initially 100 mg daily,increased according to response; max. 900 mgdaily (doses over 300 mg daily given in divideddoses); preferably after foodAllopurinol (Non-proprietary) ATablets, allopurinol 100 mg, net price 28-tab pack =£1.18; 300 mg, 28-tab pack = £1.32. Label: 8, 21, 27Brands include Caplenal c , Cosuric c , Rimapurinol cZyloric c (Aspen) ATablets, allopurinol 100 mg, net price 100-tab pack =£10.19; 300 mg, 28-tab pack = £7.31. Label: 8, 21, 27Extemporaneous formulations available seeExtemporaneous Preparations, p. 6RASBURICASECautions monitor closely for hypersensitivity; atopicallergies; may interfere with test for uric acid—consultproduct literatureContra-indications G6PD deficiency (section 9.1.5)8 Malignant disease and immunosuppression