Rapamune (sirolimus) is an immunosuppressant medicine used to prevent rejection of transplanted kidneys. Unlike tacrolimus and ciclosporin (which are calcineurin inhibitors), sirolimus works by blocking a different pathway (mTOR signalling) that immune cells use to divide and proliferate.

Sirolimus is often used in combination with calcineurin inhibitors or as a substitute for them in long-term maintenance therapy to reduce calcineurin inhibitor-related kidney toxicity.

Take Rapamune once daily, consistently at the same time. It can be taken with or without food, but always take it the same way (either with food or without) to ensure consistent absorption.

Do not eat grapefruit or drink grapefruit juice while taking Rapamune, as it significantly increases sirolimus levels.

For the oral solution, use the provided oral syringe to measure the dose. Mix with water or orange juice (at least 60 mL), stir well, and drink immediately. Do not use grapefruit juice or other juices.

Blood levels are measured regularly and the dose is adjusted to maintain a target trough concentration.

Take the missed dose as soon as you remember. If it is nearly time for the next dose, skip and continue your schedule. Contact your transplant team if you miss multiple doses.

Seek urgent medical attention. Sirolimus toxicity can cause severe immunosuppression, anaemia, and other serious effects.

• Tablets: store below 25°C, keep in original blister pack
• Oral solution: store in a refrigerator between 2°C and 8°C, protected from light. Use within one month of opening the bottle
• Keep out of reach of children

Very common side effects:

• Anaemia (low red blood cells)
• Low platelets (thrombocytopenia)
• Raised cholesterol and triglycerides: lipid-lowering therapy is often required
• High blood pressure

Common side effects:

• Infections: increased susceptibility to bacterial, viral, fungal, and opportunistic infections
• Mouth sores (aphthous ulcers)
• Skin acne-like changes
• Swelling (peripheral oedema)

Serious side effects:

• Interstitial lung disease (pneumonitis): rare but serious. Report new cough or breathlessness
• Impaired wound healing: sirolimus significantly impairs wound healing. It should be stopped before elective surgery and not restarted until wounds are healed
• Increased cancer risk, particularly skin cancers and lymphoma with long-term immunosuppression
  

Regular blood tests for levels, blood count, kidney function, liver function, and lipids are required.

Sirolimus is metabolised by CYP3A4 and is a P-glycoprotein substrate. Key interactions include:

• Grapefruit juice: significantly increases sirolimus levels. Avoid completely
• Ciclosporin: significantly increases sirolimus exposure. If you take both, your transplant team will manage the timing and dose carefully
• Rifampicin, St John's Wort, carbamazepine: reduce sirolimus levels
• Antifungals (ketoconazole, voriconazole, fluconazole): increase sirolimus levels

Tell your transplant team and pharmacist before starting any new medicine.

How does Rapamune differ from tacrolimus and ciclosporin?

Tacrolimus and ciclosporin are calcineurin inhibitors that suppress T-cells by blocking calcineurin. Sirolimus (Rapamune) targets a completely different pathway called mTOR, which controls cell division and proliferation. This different mechanism means it has a different toxicity profile: it does not cause the kidney toxicity associated with calcineurin inhibitors, but it does raise lipid levels and impairs wound healing. It is sometimes used as a calcineurin inhibitor-sparing strategy in patients whose kidneys are suffering from long-term tacrolimus or ciclosporin toxicity.

Why must I stop Rapamune before surgery?

Sirolimus blocks mTOR signalling, which is essential not only for immune cell division but also for wound healing processes. Taking sirolimus around the time of surgery significantly increases the risk of wound complications, including dehiscence (wound opening) and infection. Your transplant surgeon and team will plan when to stop and restart sirolimus around any planned procedures.

Ace provides accurate and independent information medically reviewed on prescription medications. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment.