Sirolimus

Sirolimus (Rapamune®)

(should not be prescribed as rapamycin)

Indication

As an adjunct to or substitute to a calcineurin phosphatase inhibitor for immunosuppression in patients in whom ciclosporin/tacrolimus have been implicated in allograft pathology. Anchor

Contraindications
  • Hypersensitivity to sirolimus and its derivatives.
  • Pregnancy and breast feeding
  • Presentation – 1mg and 2mg tablet
Dosage and Administration

Sirolimus is not used de-novo and is generally switched for tacrolimus. The following doses can be started and tacrolimus continued at half the current dose until sirolimus levels are therapeutic.

  • Doses should be given on an empty stomach.
  • Day 1 – 6mg daily
  • Day 2 onwards –  2mg daily adjusted according to levels
  • Check sirolimus level at 1 week
Monitoring

Target range 5-15ng/ml depending on whether it is an adjunct to or substitute for a CNI.

Note that target in SYMPHONY study when used in place of a CNI was 4/8 ng/ml and many dropped out due to adverse events despite this lower goal level.

Side Effects

Raised triglycerides and cholesterol         

Thrombocytopeania     Mouth Ulceration  Proteinuria
Anaemia Neutropenia Diarrhoea
Hypokalaemia Arthalgia Epistaxis
Delayed wound healing Lymphocele Rash
Oedema Infections PTLD
Drug Interactions

Compounds which modulate CYP3A4 activity may affect Sirolimus levels.

Drugs which may increase sirolimus levels:

Diltiazem Bromocriptine Prokinetic agents
Azole antifungals Cimetidine Protease inhibitors
Macrolide antibiotics Danazol Grapefruit juice

Drugs which may decrease sirolimus levels:  Rifampicin, anticonvulsants