Drug Action
Sirolimus is a non-calcineurin inhibiting immunosuppressant.
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Drug reference
Sirolimus is a non-calcineurin inhibiting immunosuppressant.
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Prophylaxis of organ rejection in kidney allograft recipients ▶BY MOUTH ▶Adult: Initially 6 mg for 1 dose, to be given after surgery once wound has healed, then 2 mg once daily; to be given in combination with ciclosporin and corticosteroid for 2–3 months (sirolimus doses should be given 4 hours after ciclosporin), ciclosporin should then be withdrawn over 4–8 weeks (if not possible, sirolimus should be discontinued and an alternate immunosuppressive regimen used), dose to be adjusted according to whole blood-sirolimus trough concentration DOSE EQUIVALENCE AND CONVERSION ▶The 500 microgram tablet is not bioequivalent to the 1 mg and 2 mg tablets. Multiples of 500 microgram tablets should not be used as a substitute for other tablet strengths.
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Hyperlipidaemia. increased susceptibility to infection (especially urinary-tract infection). increased susceptibility to lymphoma and other malignancies, particularly of the skin (limit exposure to UV light)
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NICE decisions ▶Immunosuppressive therapy for kidney transplant in adults (October 2017) NICE TA481 Sirolimus is not recommended as an initial treatment to prevent organ rejection in adults having a kidney transplant. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/TA481
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→Appendix 1: sirolimus
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▶Common or very common Abdominal pain. anaemia. arthralgia. ascites. constipation. diabetes mellitus. diarrhoea. dyslipidaemia. electrolyte imbalance. embolism and thrombosis. fever. haemolytic uraemic syndrome. haemorrhage. headache. healing impaired. hyperglycaemia. hypertension. increased risk of infection . leucopenia. lymphatic vessel disorders. menstrual cycle irregularities. nausea. neoplasms. neutropenia. oedema. osteonecrosis. ovarian cyst. pain. pancreatitis. pericardial effusion. proteinuria. respiratory disorders. sepsis. skin reactions. stomatitis. tachycardia. thrombocytopenia ▶Uncommon Antibiotic associated colitis. focal segmental glomerulosclerosis. hepatic failure. nephrotic syndrome. pancytopenia. post transplant lymphoproliferative disorder ▶Frequency not known Posterior reversible encephalopathy syndrome (PRES)
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Effective contraception must be used during treatment and for 12 weeks after stopping.
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Avoid unless essential—toxicity in animal Immune system and malignant disease studies.
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Discontinue breast-feeding.
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Manufacturer advises caution (risk of increased exposure). Dose adjustments Manufacturer advises maintenance dose reduction of approx. 50% in severe impairment—monitor whole blood-sirolimus trough concentration every 5–7 days until 3 consecutive measurements have shown stable blood-sirolimus concentration.
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▶Monitor whole blood-sirolimus trough concentration (Afro-Caribbean patients may require higher doses). ▶Manufacturer advises pre-dose (‘trough’) whole blood- sirolimus concentration (using chromatographic assay) when used with ciclosporin should be 4–12 micrograms/litre (local treatment protocols may differ); after withdrawal of ciclosporin pre-dose whole blood-sirolimus concentration should be 12–20 micrograms/litre (local treatment protocols may differ). ▶Close monitoring of whole blood-sirolimus concentration required if concomitant treatment with potent inducers or inhibitors of metabolism and after discontinuing them, or if ciclosporin dose reduced significantly or stopped. ▶When changing between oral solution and tablets, measurement of whole blood ‘trough’ sirolimus concentration after 1–2 weeks is recommended. ▶Therapeutic drug monitoring assays Sirolimus whole-blood concentration is measured using either high performance liquid chromatography (HPLC) or immunoassay. Switching between different immunoassays or between an immunoassay and HPLC can lead to clinically significant differences in results and therefore incorrect dose adjustments. Adjustment to the target therapeutic dose range should be made with knowledge of the assay used and corresponding reference range. ▶Monitor kidney function when given with ciclosporin; monitor lipids; monitor urine proteins.
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Food may affect absorption (take at the same time with respect to food). Sirolimus oral solution should be mixed with at least 60 mL water or orange juice in a glass or plastic container immediately before taking; refill container with at least 120 mL of water or orange juice and drink immediately (to ensure total dose). Do not mix with any other liquids.
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There can be variation in the licensing of different medicines containing the same drug. Oral solution EXCIPIENTS: May contain Ethanol ▶Rapamune (Pfizer Ltd) Sirolimus 1 mg per 1 ml Rapamune 1mg/ml oral solution sugar-free | 60 ml P £162.41 DT = £162.41 Tablet ▶Rapamune (Pfizer Ltd) Immune system and malignant disease Sirolimus 500 microgram Rapamune 0.5mg tablets | 30 tablet P £69.00 DT = £69.00 Sirolimus 1 mg Rapamune 1mg tablets | 30 tablet P £86.49 DT = £86.49 Sirolimus 2 mg Rapamune 2mg tablets | 30 tablet P £172.98 DT = £172.98
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Patient or carers should be given advice on how to administer sirolimus. Patients should be advised to avoid excessive exposure to UV light.
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Initially 6 mg for 1 dose, to be given after
First-line fragment. Read the complete Indications and Dose section above.
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