Sirolimus

Treatment should be initiated by and remain under the guidance of an appropriately qualified specialist in transplantation. Initial therapy (2 to 3 months post-transplantation): optimise with a tapering regimen of steroids and ciclosporin microemulsion; suggested ciclosporin trough concentration ranges for the first 2-3 months are 150-400 ng/mL. To minimise variability, take sirolimus at the same time in relation to ciclosporin — 4 hours after the ciclosporin dose. Maintenance therapy: ciclosporin should be progressively discontinued over 4 to 8 weeks and the sirolimus dose adjusted to obtain whole blood trough levels of 12 to 20 ng/mL; sirolimus should be given with corticosteroids. If ciclosporin withdrawal is unsuccessful or cannot be attempted, the combination of ciclosporin and sirolimus should not be maintained for more than 3 months post-transplantation. On average the sirolimus dose will need to be about 4-fold higher after ciclosporin is stopped. Dose adjustments during maintenance can usually be based on simple proportion: new dose = current dose x (target concentration / current concentration). When a considerable increase in trough concentration is needed, a loading dose may be added: loading dose = 3 x (new maintenance dose - current maintenance dose). Monitor trough concentrations at least 3 to 4 days after a loading dose, and base adjustments on more than a single trough level obtained more than 5 days after a previous dosing change. Patients can be switched from oral solution to tablets on a mg per mg basis; check a trough concentration 1 or 2 weeks after switching formulation or tablet strength. SEPARATE INDICATION — sporadic lymphangioleiomyomatosis (S-LAM): initial dose 2 mg/day; measure whole blood trough concentrations in 10 to 20 days and adjust to maintain 5 to 15 ng/mL; continue a new maintenance dose for at least 7 to 14 days before further adjustment; once stable, perform therapeutic drug monitoring at least every 3 months; reassess benefit when used long-term (no controlled data beyond one year). Trough ranges quoted are for chromatographic methods and are not interchangeable with immunoassay values. Hepatic impairment: reduce the maintenance dose by approximately one-half in severe hepatic impairment (the loading dose does not need modification) and monitor trough levels closely — in severe hepatic impairment monitor every 5 to 7 days until 3 consecutive stable trough levels. Black patients: limited information indicates Black renal transplant recipients may require higher doses and trough levels; data are too limited for specific recommendations. Elderly: clinical studies did not include sufficient patients above 65 years. Multiples of 0.5 mg tablets should not be used as a substitute for the 1 mg tablet or for other strengths. Paediatric: the safety and efficacy of sirolimus in children and adolescents less than 18 years of age have not been established and NO recommendation on a posology can be made. Note: eMC section 4.5 (interactions) was not present in the fetched bundle — the interaction entries below are drawn from §4.2/§4.4 only; clinician to source the full §4.5 list.