BNF for Children 2011-2012

BNFC 2011–2012 8.1.1 Alkylating drugs 419LEVOFOLINIC ACIDNote Levofolinic acid is an isomer of folinic acidCautions see Folinic acidSafe PracticeIntrathecal injection contra-indicatedPregnancy see Folinic acidBreast-feeding see Folinic acidSide-effects see Folinic acidIndication and doseReduction of methotrexate-induced toxicity. By intramuscular injection or by intravenousinjection or by intravenous infusionSee notes above. Consult local treatment protocolfor detailsMethotrexate overdose. By intramuscular injection or by intravenousinjection or by intravenous infusionSee notes above. Consult local treatment protocolfor detailsCalcium levofolinate(Calcium levoleucovorin)Calcium Levofolinate (Non-proprietary)Injection, levofolinic acid (as calcium salt) 10 mg/mL,net price 17.5-mL vial = £84.63Isovorin c (Wyeth) AInjection, levofolinic acid (as calcium salt) 10 mg/mL,net price 2.5-mL vial = £11.62, 17.5-mL vial = £81.33Disodium levofolinateLevofolinic Acid (Non-proprietary) AInjection, levofolinic acid (as disodium salt) 50 mg/mL, net price 1-mL vial = £24.70, 4-mL vial = £80.40Urothelial toxicityHaemorrhagic cystitis is a common manifestation ofurothelial toxicity which occurs with the oxazaphosphorines,cyclophosphamide and ifosfamide; it is causedby the metabolite acrolein. Adequate hydration is essentialto reduce the risk of urothelial toxicity. Mesna reactsspecifically with acrolein in the urinary tract, preventingtoxicity. Mesna is given for the same duration as cyclophosphamideor ifosfamide. It is generally given intravenously;the dose of mesna is equal to or greater thanthat of the oxazaphosphorine. For the role of nebulisedmesna as a mucolytic in cystic fibrosis, see section 3.7.MESNAContra-indications hypersensitivity to thiol-containingcompoundsPregnancy not known to be harmfulSide-effects nausea, vomiting, colic, diarrhoea, fatigue,headache, limb and joint pains, depression, irritability,rash, hypotension and tachycardia; rarelyhypersensitivity reactions (more common in patientswith auto-immune disorders)Licensed use not licensed for use in childrenIndication and doseUrothelial toxicity following oxazaphosphorinetherapy. By intravenous injection or by continuousintravenous infusionSee notes above. Consult local treatment protocolfor detailsMucolytic in cystic fibrosis section 3.7Mesna (Non-proprietary) ATablets, f/c, mesna 400 mg, net price 10-tab pack =£42.90; 600 mg, 10-tab pack = £61.10Injection, mesna 100 mg/mL, net price 4-mL amp =£3.95; 10-mL amp = £9.77Note For oral administration contents of ampoule are takenin a flavoured drink such as orange juice or cola which maybe stored in a refrigerator for up to 24 hours in a sealedcontainer8.1.1 Alkylating drugsExtensive experience is available with these drugs,which are among the most widely used in cancerchemotherapy. They act by damaging DNA, thus interferingwith cell replication. In addition to the side-effectscommon to many cytotoxic drugs (section 8.1), problemsassociated specifically with alkylating drugsinclude:. an adverse effect on gametogenesis which may bereversible, particularly in females; amenorrhoeamay also occur, which also may be reversible;. a marked increase in the incidence of secondarytumours and leukaemia, particularly when alkylatingdrugs are combined with extensive irradiation;. fluid retention with oedema and dilutional hyponatraemiain younger children; the risk of this complicationis higher in the first 2 days and also whengiven with concomitant vinca alkaloids;. urothelial toxicity with intravenous use; adequatehydration may reduce this risk; mesna (section 8.1)provides further protection against urotoxic effectsof cyclophosphamide and ifosfamide.BUSULFAN(Busulphan)Cautions see section 8.1 and notes above; monitor fullblood count regularly throughout treatment; monitorliver function; previous mediastinal or pulmonaryradiation therapy; avoid in acute porphyria (but seesection 9.8.2); interactions: Appendix 1 (busulfan)Hepatic impairment manufacturer advises monitorhepatic function—no information availablePregnancy avoid (teratogenic in animals); manufacturersadvise effective contraception during and for 6months after treatment in men or women; see alsoPregnancy and Reproductive Function, p. 416Breast-feeding discontinue breast-feedingSide-effects see section 8.1 and notes above; alsohepatotoxicity (including hepatic veno-occlusive disease,hyperbilirubinaemia, jaundice, and fibrosis);cardiac tamponade in thalassaemia; pneumonia, skinhyperpigmentation; rarely progressive pulmonary8 Malignant disease and immunosuppression