BNF for Children 2011-2012

508 10.1.3 Drugs that suppress the rheumatic disease process BNFC 2011–201210 Musculoskeletal and joint diseasestoxicity, hair depigmentation, hair loss, and discolorationof skin, nails, and mucous membranes. Side-effectsthat occur rarely include blood disorders (includingthrombocytopenia, agranulocytosis, and aplastic anaemia),mental changes (including emotional disturbancesand psychosis), myopathy (including cardiomyopathyand neuromyopathy), acute generalised exanthematouspustulosis, exfoliative dermatitis, Stevens-Johnsonsyndrome, photosensitivity, and hepatic damage; angioedemaand bronchospasm have also been reported.Important: very toxic in overdosage—immediateadvice from poisons centres essential (see also p. 29).HYDROXYCHLOROQUINE SULPHATECautions see notes aboveHepatic impairment use with caution in moderate tosevere impairmentRenal impairment manufacturer advises caution andmonitoring of plasma-hydroxychloroquine concentrationin severe impairmentPregnancy see notes aboveBreast-feeding see notes aboveSide-effects see notes aboveIndication and doseJuvenile idiopathic arthritis, systemic anddiscoid lupus erythematosus, dermatologicalconditions caused or aggravated by sunlight. By mouthChild 1 month–18 years based on ideal bodyweight,5–6.5 mg/kg (max. 400 mg) once dailyHydroxychloroquine (Non-proprietary) ATablets, hydroxychloroquine sulphate 200 mg, netprice 60-tab pack = £5.10. Label: 21, counselling,antacids (see below)Brands include Quinoric cCounselling Avoid antacids for at least 4 hours before orafter hydroxychloroquine to reduce possible interferencewith hydroxychloroquine absorptionPlaquenil c (Sanofi-Aventis) ATablets, f/c, hydroxychloroquine sulphate 200 mg,net price 60-tab pack = £5.25. Label: 21, counselling,antacids (see below)Counselling Avoid antacids for at least 4 hours before orafter hydroxychloroquine to reduce possible interferencewith hydroxychloroquine absorptionExtemporaneous formulations available seeExtemporaneous Preparations, p. 6Drugs affecting the immune responseMethotrexate, given as a once weekly dose, is thedisease-modifying antirheumatic drug of choice in thetreatment of juvenile idiopathic arthritis and also has arole in juvenile dermatomyositis, vasculitis, uveitis, systemiclupus erythematosus, localised scleroderma, andsarcoidosis; for these indications it is given by thesubcutaneous, oral, or rarely, the intramuscular route.Absorption from intramuscular or subcutaneous routesmay be more predictable than from the oral route; if theoral route is ineffective subcutaneous administration isgenerally preferred. Regular full blood counts (includingdifferential white cell count and platelet count), renaland liver function tests are required. Folic acid mayreduce mucosal or gastro-intestinal side-effects ofmethotrexate. The dosage regimen for folic acid hasnot been established—in children over 2 years a dose of5 mg weekly [unlicensed indication], may be given on adifferent day from the methotrexate.Azathioprine may be used in children for vasculitiswhich has failed to respond to other treatments, for themanagement of severe cases of systemic lupus erythematosusand other connective tissue disorders, in conjunctionwith corticosteroids for patients with severe orprogressive renal disease, and in cases of polymyositiswhich are resistant to corticosteroids. Azathioprine hasa corticosteroid-sparing effect in patients whosecorticosteroid requirements are excessive.Ciclosporin is rarely used in juvenile idiopathic arthritis,connective tissue diseases, vasculitis, and uveitis; it maybe considered if the condition has failed to respond toother treatments.AZATHIOPRINECautions section 8.2.1Contra-indications section 8.2.1Hepatic impairment section 8.2.1Renal impairment section 8.2.1Pregnancy section 8.2.1Breast-feeding section 8.2.1Side-effects section 8.2.1Indication and doseSystemic lupus erythematosus, vasculitis,auto-immune conditions usually when corticosteroidtherapy alone has proved inadequatesee also notes above. By mouthChild 1 month–18 years initially 1 mg/kg daily,adjusted according to response to max. 3 mg/kgdaily (consider withdrawal if no improvementwithin 3 months)Inflammatory bowel disease section 1.5.3Transplantation rejection section 8.2.1PreparationsSection 8.2.1METHOTREXATECautions section 8.1.3; see advice below (blood count,gastro-intestinal, liver, and pulmonary toxicity);extreme caution in blood disorders (avoid if severe);risk of accumulation in pleural effusion or ascites—drain before treatment; full blood count and liverfunction tests before starting treatment repeatedfortnightly for at least the first 4 weeks and at thisfrequency after any change in dose until therapystabilised, thereafter monthly; renal function testsbefore starting treatment and then regularly duringtreatment; children or their carers should report allsymptoms and signs suggestive of infection, especiallysore throat; treatment with folinic acid (as calciumfolinate, section 8.1) may be required in acutetoxicity; check immunity to varicella-zoster and considervaccination (section 14.4) before initiating therapy;acute porphyria (section 9.8.2); interactions: seebelow and Appendix 1 (methotrexate)Blood count Bone marrow suppression can occur abruptly;factors likely to increase toxicity include renal impairmentand concomitant use with another anti-folate drug. A clini-