BNF for Children 2011-2012

436 8.2.2 Corticosteroids and other immunosuppressants BNFC 2011–20128 Malignant disease and immunosuppressionTACROLIMUSCautions monitor blood pressure, ECG (important:see cardiomyopathy below), fasting blood-glucoseconcentration, haematological and neurological(including visual) parameters, electrolytes, hepaticand renal function; monitor whole blood-tacrolimustrough concentration (especially during episodes ofdiarrhoea)—consult local treatment protocol fordetails; QT-interval prolongation; neurotoxicity;increased risk of infections, malignancies, and lymphoproliferativedisorders; avoid excessive exposureto UV light (including sunlight); pregnancy (excludebefore starting); interactions: Appendix 1 (tacrolimus)Skilled tasks May affect performance of skilled tasks (e.g.driving)Contra-indications hypersensitivity to macrolides;avoid concurrent administration with ciclosporin(care if patient has previously received ciclosporin)Hepatic impairment dose reduction may be necessaryin severe impairmentPregnancy avoid unless potential benefit outweighsrisk—risk of premature delivery, intra-uterine growthrestriction, and hyperkalaemia; toxicity in animalstudiesBreast-feeding avoid—present in milkSide-effects nausea, vomiting, diarrhoea, constipation,dyspepsia, flatulence, bloating, weight changes,anorexia, gastro-intestinal inflammation, ulceration,and perforation, hepatic dysfunction, jaundice,cholestasis, ascites, bile-duct abnormalities, oedema,tachycardia, hypertension, haemorrhage, thromboembolicand ischaemic events, dyspnoea, pleuraleffusion, parenchymal lung disorders, sleep disturbances,tremor, headache, peripheral neuropathy,mood changes, depression, confusion, anxiety, psychosis,seizures, paraesthesia, dizziness, renal impairment,renal failure, renal tubular necrosis, urinaryabnormalities, hyperglycaemia, electrolyte disturbances(including hyperkalaemia, hypokalaemia, andhyperuricaemia), blood disorders (including anaemia,leucopenia, pancytopenia, and thrombocytopenia),arthralgia, muscle cramp, visual disturbances, photophobia,tinnitus, impaired hearing, alopecia, sweating,acne; less commonly paralytic ileus, gastro-intestinalreflux disease, peritonitis, pancreatitis, heart failure,arrhythmia, cardiac arrest, cerebrovascular accident,cardiomyopathy (important: see Cardiomyopathybelow), palpitation, respiratory failure, coma, speechdisorder, amnesia, paralysis, influenza-like symptoms,encephalopathy, coagulation disorders, cataract,photosensitivity, hypoglycaemia, dysmenorrhoea,hypertonia, dermatitis; rarely pericardial effusion,respiratory distress syndrome, posterior reversibleencephalopathy syndrome, dehydration, thromboticthrombocytopenic purpura, blindness, toxic epidermalnecrolysis, hirsutism; very rarely myasthenia,haemorrhagic cystitis, Stevens Johnson syndromeCardiomyopathy Cardiomyopathy has been reported inchildren. Children should be monitored by echocardiographyfor hypertrophic changes—consider dose reduction or discontinuationif these occurLicensed use Advagraf c not licensed for use inchildrenIndication and doseSee under preparations and consult local treatmentprotocolsAtopic eczema (topical use) section 13.5.3ImportantAdoport c , Prograf c , Modigraf c , Vivadex c , andAdvagraf c (tacrolimus): serious medication errorsThere are 3 different oral formulations of tacrolimus:. Adoport c , Prograf c , and Vivadex c are immediate-releasecapsules taken twice daily, once in the morning and once inthe evening;. Modigraf c granules are used to prepare an immediatereleaseoral suspension which is taken twice daily, once inthe morning and once in the evening;. Advagraf c is a prolonged-release capsule that is takenonce daily in the morning.Switching between different oral formulations oftacrolimus requires careful therapeutic monitoring.Changes to oral tacrolimus therapy should be madeonly under the close supervision of a transplant specialist.Administration For continuous intravenous infusionover 24 hours, dilute to a concentration of 4–100 micrograms/mL with Glucose 5% or SodiumChloride 0.9%, to a total volume between 20–500 mL.Tacrolimus is incompatible with PVCAdoport c (Sandoz) ACapsules, tacrolimus (as monohydrate) 500 micrograms(white/ivory), net price 50-cap pack = £50.50;1 mg (white/brown), 50-cap pack = £65.52, 100-cappack = £131.02; 5 mg (white/orange), 50-cap pack =£242.05. Label: 23, counselling, skilled tasksDoseProphylaxis of graft rejection following liver transplantation,starting 12 hours after transplantation. By mouthNeonate initially 150 micrograms/kg twice daily,adjusted according to whole-blood concentrationChild 1 month–18 years initially 150 micrograms/kgtwice daily, adjusted according to whole-blood concentrationProphylaxis of graft rejection following kidneytransplantation, starting within 24 hours of transplantation. By mouthNeonate initially 150 micrograms/kg twice daily,adjusted according to whole-blood concentrationChild 1 month–18 years initially 150 micrograms/kgtwice daily, adjusted according to whole-blood concentrationNote A lower initial dose of 100 micrograms/kg twicedaily has been used in adolescents to prevent very high‘trough’ concentrationsProphylaxis of graft rejection following heart transplantationwithout antibody induction, starting within12 hours of transplantation. By mouthNeonate initially 150 micrograms/kg twice daily as soonas clinically possible (8–12 hours after discontinuation ofintravenous infusion), adjusted according to whole-bloodconcentrationChild 1 month–18 years initially 150 micrograms/kgtwice daily as soon as clinically possible (8–12 hours afterdiscontinuation of intravenous infusion), adjustedaccording to whole-blood concentration