Sirolimus (Whole Blood)

Specimen Required

3cc EDTA BLOOD (CBC VIAL)

Fasting Required

Purpose of the Test

To determine the concentration of sirolimus in the blood in order to establish a dosing strategy, maintain therapeutic levels, and detect toxic levels

When this test is required

Sirolimus is requested frequently at the start of therapy. Because of the long time it takes to clear the drug from the body (long half-life), sirolimus concentrations may take some time to reach a steady concentration in the blood. Once dosages have been established and the drug has been shown to be well tolerated, then the frequency of sirolimus testing may decrease.The test may be performed whenever there is a change in dose or formulation (oral solution to tablets or vice versa), a change in other medications if liver function is impaired or whenever patients have symptoms that suggest side effects, toxicity, or organ rejection.Even when taking sirolimus properly, some patients may have side effects and experience complications such as infections and slow healing. Side effects that may warrant testing to check the drug level include: Abdominal pain Constipation Diarrhoea Fever Headache High blood pressure Sleeplessness (insomnia) Nausea Sensitivity to sunlight Weight gainIf any of the above persist or become severe, the doctor should be notified.In addition, some of the more dangerous signs and symptoms of sirolimus toxicity include: Cough/shortness of breath Chest pain Fast heart rate Pale skin Easy bruising or excessive bleedingMonitoring is necessary as long as the patient is taking sirolimus.

What the Test Detects

This test measures the amount of sirolimus in the blood. Sirolimus is a newer immunosuppressive drug that is given to patients who have had an organ transplant. Normally, the immune system recognises a transplanted organ as ‘foreign’ and begins to attack it, leading to rejection. Sirolimus limits this response and helps prevent organ rejection by inhibiting immune cell activation and prliferation, and antibody production.Siroliums is typically taken by mouth (orally) and, after ingestion, is absorbed from the digestive tract. The concentration peaks in the blood within a couple of hours and then gradually declines. Only a small percentage of the dose taken is present in a form that the body can use. Sirolimus has a half-life of about 60 hours. It is metabolised by the liver into several new compounds, and is removed from the body in the stool (more than 90%) and urine (less than 2%). Sirolimus is currently approved for use in adults who have kidney transplants. It appears to be less toxic to the kidneys than other drugs and can be given in conjunction with the other immunosuppressive drugs ciclosporin and tacrolimus. Studies to evaluate its use in other age groups and types of organ transplantation, such as lung, are in progress. Like other immunosuppressive agents, sirolimus may cause side effects and adverse reactions, and is associated with an increased risk of infection and the development of lymphoma.Sirolimus levels in the blood must be maintained within a narrow concentration range. If the concentration is too low, organ rejection may occur; if it is too high, then the patient may have symptoms associated with toxicity. The sirolimus blood level is usually measured as ‘trough’ level, with blood collection just prior to the next dose – when the drug concentration in the blood is at its lowest. Typically, sirolimus is initially given with ciclosporin and corticosteroids (siroliumus given 4 hours after ciclosporin).Dosages must be tailored to the individual, and sirolimus and ciclosporin must both be monitored.Often, patients will begin with a high dose of sirolimus at the beginning of treatment which is then tapered down to a lower dose. Ciclosporin is normally withdrawn after 2-3 months.Sirolimus is usually taken once a day at set intervals. Food may affect absorption, and the drug should be taken at the same time each day with respect to food. How is the sample collected for testing?A blood sample is obtained by inserting a needle into a vein in the arm.Is any test preparation needed to ensure the quality of the sample?Have the sample collected immediately prior to the next dose, or as directed by your doctor

Preparation for the Test

Have the sample collected immediately prior to the next dose, or as directed by your doctor

Sample Requirements

A blood sample taken from a vein in your arm

Additional Notes

Drugs that slow down or accelerate the metabolism of sirolimus may affect blood levels. Drugs that can increase sirolimus blood levels include antifungal medication (itraconazole, ketoconazole and voriconazole), clarithromycin, telithromycin, erythromycin, isoniazid, diltiazem, protease inhibitors, and quinidine. Those that can decrease sirolimus levels include carbamazepine, phenobarbital, phenytoin and rifampicin. Grapefruit juice and herbal supplements such as St. John’s Wort must be avoided while taking sirolimus.Patients should not alter their dose or the time that they take their dose without consulting their doctor. Sirolimus should be taken consistently with respect to meals. Women should not become pregnant while taking sirolimus. Those considering pregnancy should talk to their doctor about associated risks.To help reduce the chances of developing skin cancer it is important to protect the skin from the effects of ultra-violet light while taking Rapamune. Patients should try reducing the time skin is exposed to sunlight or ultraviolet light by using a high protection sun screen and by wearing appropriate clothing.Patients taking sirolimus should also talk to their doctor before getting any vaccines.

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