To determine the level of sirolimus in the blood in order to establish a dosing regimen, 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 drawn from a vein
None; the sample is typically collected 12 hours after the last dose and immediately prior to the next dose, or as directed by your healthcare provider
Sirolimus, also called rapamycin, is a drug that is used to suppress the immune system in people who have had kidney transplants. It is given in combination with other drugs to prevent rejection of transplanted kidneys. This test measures the amount of sirolimus in the blood.
Normally, a person's immune system recognizes a transplanted organ as foreign and begins to attack it. Sirolimus limits this response and helps to prevent organ rejection by inhibiting the activation and production of white blood cells called T-lymphocytes. It also inhibits antibody production.
Sirolimus is typically taken by mouth (orally) and, after ingestion, is absorbed from the digestive tract. The drug's concentration peaks in the blood in approximately two hours and then gradually declines. It is metabolized by the liver and in the gut and is eliminated from the body in the stool (more than 90%) and urine (less than 2%).
The U.S. Food and Drug Administration (FDA) has currently approved sirolimus for use in people 13 years of age and older who have kidney transplants to prevent acute rejection. It appears to be less toxic to the kidneys than other options and can be given in conjunction with the other immunosuppressant drugs cyclosporine and tacrolimus. Studies to evaluate its use in other age groups and types of organ transplantation, such as liver or lung, are ongoing, but so far, no data have convinced the FDA that sirolimus is appropriate for children under 13. Like other immunosuppressant agents, sirolimus may cause side effects and adverse reactions and is associated with an increased risk of infection and the development of lymphoma and skin cancer.
The sirolimus level must be monitored over time with laboratory tests because the drug has a narrow therapeutic index, which is the range between minimal effective concentration and minimum toxic concentration. If the drug concentration is too low, organ rejection may occur; if it is too high, symptoms associated with toxicity may develop, such as low platelet, low white blood cell, and high triglyceride levels. The sirolimus blood test is usually measured as a "trough" level, with blood collection just prior to the next dose – at the drug's lowest concentration in the blood.
Typically, sirolimus is given with cyclosporine and corticosteroids. Dosages must be tailored to the individual, and sirolimus and cyclosporine must both be monitored. Often, people will begin with an initial higher dose (loading dose) of sirolimus and then are tapered to a lower dose. In people considered at low risk for complications, cyclosporine may be decreased or stopped after 2-4 months and sirolimus concentrations will be increased.
How is it used?
The sirolimus test is used to monitor the level of the drug over time in kidney transplant recipients who are taking the drug to prevent organ rejection. This test measures the amount of drug in the blood to determine whether the concentration is within the therapeutic range and is below the toxic level. Treatment with sirolimus must be monitored because the range in which the drug is effective but not toxic is very narrow.
When is it ordered?
Sirolimus is ordered frequently at the start of therapy when the drug concentration reaches an equilibrium (stead state) in the blood. Because of the long time that it takes to clear the drug from the body (its long half-life), the sirolimus concentration may take several days to settle at a steady state. Once dosages have been optimized for the individual and are well tolerated, then the frequency of sirolimus testing may be reduced.
The test may be performed whenever there is a change in dose, a change in other medications, or whenever the transplant recipient has symptoms that suggest side effects, toxicity, or organ rejection.
Even when taking sirolimus properly, some people may have side effects and experience complications, such as infections and slow healing. Other side effects include:
- Increased levels of lipids in the blood
- Sleeplessness (insomnia)
- Sensitivity to sunlight
- Weight gain
If any of the above persists or becomes severe, the healthcare provider should be notified.
- Cough, shortness of breath
- Chest pain
- Fast heart rate
- Pale skin
- Unusual bleeding or bruising
- Swollen, red, cracked, scaly skin
- Hives, rash, itching
- Difficulty swallowing
- Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles or lower legs
Monitoring is necessary as long as the transplant recipient takes sirolimus.
What does the test result mean?
A level that is higher than the established therapeutic range may cause symptoms associated with toxicity. An inappropriately low level may lead to rejection of the transplanted organ. Depending on the results, a healthcare practitioner may adjust the dose that the person is given.
If the person is also taking other immunosuppressants or medications, then that person should work closely with their healthcare provider and transplant team to ensure that there is no potential interactions between the medications.
Is there anything else I should know?
Drugs or food that inhibit or accelerate the metabolism of sirolimus may affect blood levels. Be sure to tell your healthcare provider about any drugs or supplements you are taking. Examples of drugs that can increase sirolimus blood levels include antifungal medications, clarithromycin, erythromycin, isoniazid, protease inhibitors, and quinidine. Examples of those that can decrease sirolimus levels include carbamazepine, phenobarbital, phenytoin, rifampin and nafcillin. Grapefruit juice and herbal supplements such as St. John's Wort should be avoided while taking sirolimus.
People taking sirolimus should not alter their dose or the time that they take their dose without consulting their healthcare provider. Sirolimus should be taken consistently with respect to meals. Women should not become pregnant while taking sirolimus. Those considering pregnancy should talk to their health practitioner about associated risks.
Sirolimus should not be used with certain drugs that weaken the immune system and increase risk of infection. These include voriconazole, natalizumab, and rituximab. People taking sirolimus should also talk to their healthcare provider before getting any vaccines.
Besides sirolimus testing, what other tests might be done and why?
How long will I need to be on sirolimus?
Transplant recipients must take immunosuppressants — including sirolimus or other drugs, often in combination — throughout their lives. Talk to your healthcare provider about the best choices for your condition; they may change over time.
Who orders sirolimus tests?
Sirolimus will usually be monitored by the healthcare provider and transplant team that performed your surgery or by a healthcare practitioner who has specific knowledge of transplantation and your condition.
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 will have different reference ranges. Your healthcare provider will usually send your tests consistently to one laboratory for testing so that your levels can trend over time by the same testing method.
Is sirolimus given to patients who receive organs other than kidneys or have other conditions?
Sirolimus also is used sometimes to treat psoriasis. Also, it was approved by the FDA in May 2015 for the treatment of lymphangioleiomyomatosis, a rare, progressive disease that affects the lungs, kidneys and the lymphatic system. This medication should not be given to prevent rejection of liver or lung transplants because it can cause serious and deadly side effects.
Should I tell my other healthcare 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, to get vaccinations, and may increase the risk of developing certain cancers (such as skin cancers and lymphoma).