sirolimus: clinical use

Prescribing considerations

• Specialist initiation and continuing oversight are required.
• Review infection risk, immunisation status, total immunosuppressive burden and potential CYP3A4 or P-glycoprotein interactions.
• Assess renal function, proteinuria, hepatic impairment, hyperlipidaemia and wound-healing risk.
• Plan carefully around surgery because wound healing may be impaired.
• Limit ultraviolet exposure and maintain skin-cancer surveillance.
• The selected products are not established as immunosuppressive treatment for liver or lung transplantation.

Contraindications and cautions

• Hypersensitivity to sirolimus or a formulation excipient.
• The oral solution must not be used in people allergic to peanut or soya because it contains soya oil.

Monitoring

• Whole-blood trough sirolimus concentration using a consistent, understood assay method
• Full blood count
• Renal function and quantitative urinary protein
• Liver function
• Lipids and blood glucose
• Blood pressure
• Infection, respiratory symptoms, oedema and wound healing
• Skin and other malignancy surveillance

Clinical pharmacology

Sirolimus forms a complex with FKBP-12 that inhibits mTOR, suppressing lymphocyte activation and cell-cycle progression. It is a CYP3A4 and P-glycoprotein substrate with a long half-life and substantial interpatient pharmacokinetic variability.

Formulation and product differences

• Tablets should be swallowed whole; bioavailability after crushing, chewing or splitting has not been established.
• Multiples of the lowest-strength tablet are not directly interchangeable with higher-strength tablets because exposure differs.
• The oral solution requires dilution only with water or orange juice and contains soya oil, ethanol and propylene glycol.
• The tablets contain lactose and sucrose.

Oral solution

Route: Oral

Strengths: 1 mg/mL

Tablet

Route: Oral

Strengths: 0.5 mg, 1 mg, 2 mg