Sirolimus

• Prophylaxis of organ rejection in renal transplant

• Immunsuppressive agent. An inhibitor of mammalian target of rapamycin (mTOR inhibitor)
• Rapamune®: 0.5 mg, 1 mg and 2mg tablets; and 1 mg/ml oral solution
• 0.5 mg tablets are not fully bioequivalent to higher strengths, so 2 x 0.5 mg is not equivalent to 1 x 1 mg

• Hypersensitivity to sirolimus or any of the excipients
• Oral solution contains soya oil, patients allergic to peanut or soya should not take this medicine

• Monitor trough levels: initially 4-12 ng/ml if taken in combination with ciclosporin and 8-20 ng/ml if taken without ciclosporin
• Take blood levels no more frequently than every 5 days
• Hepatic impairment: in severe hepatic impairment, maintenance dose of sirolimus must be reduced by approximately one half and trough levels monitored
• In black-african patients a higher dose and trough levels may be required to acheive the same efficacy as in non-black patients

• Infection and malignancies (esp lymphoma, skin and cervical cancer)
• Bone marrow suppression, hypertension, hyperlipidaemia, delayed wound healing, lymphocoele, hypokalaemia, delayed recovery of renal function in delayed graft function
• Rarely HUS/TTP and interstitial lung disease

• 6 mg loading dose followed by 2 mg daily titrated according to trough blood levels (4-12ng/ml)
• If used without ciclosporin, a loading dose of 10-15 mg will be required followed by a daily dose of 3-6 mg titrated according to trough levels (8-20ng/ml)
• 0.5 mg tablets are not fully bioequivalent to higher strengths, so 2 x 0.5 mg is not equivalent to 1 x 1 mg
• If changing from tablet to liquid, give the same dose and check levels after 7 days
• Afro-Caribbean patients make require higher doses

• As in normal renal function. Not dialysed

• Levels ↑ by erythromycin, ketoconazole, clarithromycin, diltiazem, grapefruit juice, verapamil
• Levels ↓ by rifampicin
• Ciclosporin increases absorbtion of sirolimus – give sirolimus 4 hours after ciclosporin, St Johns Wort. Concomitant administration of mycophonolate results in increased levels of both sirolimus and mycophenolate

Sirolimus#2 mg#see prescribing section#PO#8

• There is an increased risk of infection and certain cancers (including skin and cervical). Avoid sunbathing, use high factor sun cream and women should attend for yearly cervical smears
• Avoid live vaccines – ask your pharmacist
• Food may affect absorption. So take at the same time in relation to food. Avoid grapefruit juice
• Women of childbearing age must use contraception during sirolimus therapy and for 12 weeks after stopping. Avoid if breastfeeding
• To minimise variability sirolimus should be taken at the same time in relation to ciclosporin, four hours after the ciclosporin dose, and consistently either with or without food