Sirolimus
At a Glance
Why Get Tested?
To determine the concentration of sirolimus in the blood in order to establish a dosing strategy, maintain therapeutic levels, and detect toxic levels
When to Get Tested?
As soon as sirolimus therapy begins and whenever dose is changed. Frequently at first, then at regular intervals to monitor concentrations over time. Whenever excess or deficient levels are suspected
Sample Required?
A blood sample taken from a vein in your arm
Test Preparation Needed?
Have the sample collected 12 hours after the last dose and immediately prior to the next dose, or as directed by your doctor
The Test Sample
What is being tested?
This test measures the amount of sirolimus in the blood. Sirolimus is a relatively new 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 ciclosporine 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 siroliums blood level is usually measured as 'through' level, with blood collection just prior to the next dose - when the drug concentration in the blood is at its lowest.
Typically, sirolimus is given with ciclosporin and corticosteroids. 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 reduced or 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. If ciclosporin is also being taken, then the dosages of both drugs should be separated by several (more than 4) hours. The sirolimus blood test is usually measured as a “trough” level with blood collection is just prior to the next dose when the drug is at its lowest concentration in the blood.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
Have the sample collected 12 hours after the last dose and immediately prior to the next dose, or as directed by your doctor
The Test
How is it used?
The sirolimus test is requested to measure the amount of drug in the blood in organ transplant recipients to determine whether concentrations have reached therapeutic levels (sufficient to prevent rejection) and are below toxic levels. Monitoring is necessary because the range in which the drug is effective and not toxic is very narrow. If someone is taking both sirolimus and ciclosporine (or tacrolimus) then both drug concentrations need to be monitored. Other tests may also be requested at intervals to check organ function and the body’s blood cell counts, because sirolimus may decrease the platelet count, increase the blood lipids, and, when taken long-term with other immunosuppressants, affect kidney function.
When is it requested?
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, a change in other medications, 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:
- Constipation
- Diarrhoea
- Fever
- Headache
- High blood pressure
- Sleeplessness (insomnia)
- Nausea
- Sensitivity to sunlight
- Weight gain
If any of the above persist or become severe, the doctor should be notified.
In addition, some of the more dangerouse signs and symptoms of sirolimus toxicity include:
- Cough/shortness of breath
- Chest pain
- Fast heart rate
- Pale skin
- Easy bruising or excessive bleeding
Monitoring is necessary as long as the patient is taking sirolimus.
What does the test result mean?
A level that is higher than the established therapeutic range may cause symptoms associated with toxicity. A level that is too low may lead to rejection of the transplanted organ. Depending on the results, a doctor may adjust the dose of drug.
If a patient is also taking other immunosuppressants or medications, then they should work closely with their doctor and transplant team to ensure that there is no potential interaction between the medications.
Is there anything else I should know?
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 UV light while you are 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.
Common Questions
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Article Sources
NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
