To determine the concentration of sirolimus, an anti-organ transplant rejection drug, in the blood in order to establish a dosing strategy, maintain therapeutic levels, and detect toxic levels
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
A blood sample taken from a vein in your arm
Have the sample collected immediately prior to the next dose, or as directed by your doctor
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 proliferation, 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 (the time it takes for the concentration of the drug to fall by half). 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, for example sensitivity to sunlight, 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 once the operation wound has healed (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 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 ciclosporin (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. Creatinine, a test measured to asses kidney function should be monitored regularly when sirolimus and ciclosporin or tacrolimus are being given together.
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, 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
- High blood pressure
- Sleeplessness (insomnia)
- 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 dangerous 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 should be avoided while taking sirolimus as they can affect the drug concentration.
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.
How long will I need to be on sirolimus?
Who requests sirolimus tests?
Where are sirolimus tests performed?
Sirolimus tests may be performed in a local hospital laboratory, but may also be sent to a reference laboratory. Because different laboratories use different methods, each laboratory may have different target ranges. Your doctor will usually send your tests consistently to one laboratory for testing so that trends in your results can be monitored over time by the same testing method.
Should I tell my other health care providers that I am taking sirolimus?
Yes, this is important information for them, partially because of drug interactions and partially because of the immunosuppressive action of sirolimus. Sirolimus can affect your ability to heal or to receive vaccinations, and may increase the risk of developing certain cancers (such as skin cancers and lymphoma).