Tacrolimus

eMC §4.2 (Adoport 0.5 mg Hard Capsules, emc product 585): 'Dosage recommendations - Kidney transplantation. Prophylaxis of transplant rejection - adults. Oral tacrolimus therapy should commence at 0.20-0.30 mg/kg/day administered as two divided doses (e.g. morning and evening).' PER-DAY, NOT PER-DOSE: the figure above is a daily total that is then split in two — do not read it as the size of each administration. THE RECOMMENDED INITIAL DOSAGES ARE A GUIDELINE ONLY: dosing should primarily be based on clinical assessments of rejection and tolerability in each individual patient, aided by whole-blood trough level monitoring, and doses are usually reduced in the post-transplant period. TARGET WHOLE BLOOD TROUGH LEVELS: blood trough levels should be drawn approximately 12 hours post-dosing, just prior to the next dose, monitored approximately twice weekly in the early post-transplant period and then periodically during maintenance, and after any dose or regimen change or co-administration of interacting substances. Clinical study analysis suggests most patients can be successfully managed if trough levels are kept below 20 ng/ml; in practice levels have generally been 10-20 ng/ml in kidney and heart transplant patients in the early post-transplant period and 5-15 ng/ml during maintenance (5-20 ng/ml early and 5-15 ng/ml maintenance in liver recipients). FORMULATION SWITCHING (§4.2/§4.4): inadvertent, unintentional or unsupervised switching between immediate- and prolonged-release tacrolimus formulations is unsafe and has led to graft rejection or serious adverse events; patients must be maintained on a single formulation with its corresponding daily dosing regimen, any change made only under close transplant-specialist supervision, with therapeutic drug monitoring and dose adjustment after any conversion. OTHER INDICATIONS IN THE SAME SPC (adults, initial oral doses, for reference only — this page is the renal page): liver transplantation 0.10-0.20 mg/kg/day in two divided doses starting about 12 hours after surgery (IV alternative 0.01-0.05 mg/kg/day); heart transplantation following antibody induction 0.075 mg/kg/day in two divided doses starting within 5 days of surgery (IV alternative 0.01-0.02 mg/kg/day), or an alternative published strategy of 2 to 4 mg per day orally within 12 hours post-transplant in patients without organ dysfunction; lung transplantation 0.10-0.15 mg/kg/day; pancreas 0.2 mg/kg/day; intestinal transplantation 0.3 mg/kg/day. Rejection therapy in adults converted to tacrolimus: initial oral dose 0.15 mg/kg/day in two divided doses. CONVERSION FROM CICLOSPORIN: initiate only after considering ciclosporin blood concentrations and the clinical condition; delay dosing if ciclosporin levels are elevated — in practice tacrolimus has been started 12-24 hours after discontinuation of ciclosporin, with continued monitoring of ciclosporin levels afterwards. HEPATIC IMPAIRMENT: dose reduction may be necessary in severe liver impairment to keep trough levels in range. ELDERLY: no evidence currently available to indicate that dosing should be adjusted. DURATION: to suppress graft rejection, immunosuppression must be maintained, so no limit to the duration of oral therapy can be given. PRESCRIBER RESTRICTION: tacrolimus should only be prescribed, and changes in immunosuppressive therapy initiated, by physicians experienced in immunosuppressive therapy and the management of transplant patients. PAEDIATRIC — HELD OUT OF THE STRUCTURED FIELD ON PURPOSE (see below): §4.2 states for kidney transplantation 'Prophylaxis of transplant rejection - children: An initial oral dose of 0.30 mg/kg/day should be administered in two divided doses (e.g. morning and evening). If the clinical condition of the patient prevents oral dosing, an initial intravenous dose of 0.075-0.100 mg/kg/day should be administered as a continuous 24-hour infusion.' §4.2 adds that in general paediatric patients require doses 1½ to 2 times higher than adult doses to achieve similar blood levels. Verify all paediatric use against a children's formulary. SOURCE CAVEATS: the fetched §4.4 and §4.8 were cut off at the source-fetch limit, and §4.5 was not captured — review the full SPC. SUPERSEDES EARLIER HOLD: a previous draft was held because it stored the per-DAY figure 0.30 mg/kg/day in the structured per-administration field paedDose.dosePerKg, which the drug page renderer and DrugDoseCalculator treat as the size of each dose — a 20 kg child would have been shown 6 mg as each of two daily doses, i.e. twice the SPC initial daily dose of a narrow-therapeutic-index immunosuppressant, with no cap applied. paedDose is therefore deliberately null here and the paediatric regimen is stated in full above as a daily total.