To determine the concentration of mycophenolic acid (MPA) in the blood in order to monitor levels, and prevent toxicity
As soon as mycophenolate therapy begins and whenever the dose is changed. May be requested frequently at first, then at regular intervals. Whenever excess or deficient levels of MPA are suspected.
A blood sample taken from a vein in your arm
This test measures the amount of mycophenolic acid in the blood. Mycophenolic acid is the active metabolite of mycophenolate, a drug that is usually given to patients who have had a heart, kidney, or liver transplant to help prevent rejection. Normally, the immune system defends the body against infections, and can distinguish between “self”, the body’s own constituents, and “nonself” or“foreign” materials. The immune system recognises a transplanted organ as foreign and begins to attack it. In the case of autoimmune disorders, the immune system mistakenly targets the body’s own cells and tissues, causing damage and inflammation. Mycophenolic acid belongs to a group of immunosuppressant drugs and helps to prevent organ rejection, tissue inflammation, and damage. It acts by reducing the formation of an enzyme that is necessary for increasing the number of lymphocytes (immune cells). This action causes a reduction in immune system function and antibody production, reducing the body’s immune response to transplanted organs or to its own tissues and cells.
Mycophenolate is given to organ transplant patients in conjunction with other immunosuppressant drugs, such as ciclosporin and tacrolimus. In the treatment of autoimmune disorders, mycophenolate may be used as a single agent (although the patient may also be taking other medications). There are two formulations of the drug available, mycophenolate mofetil and mycophenolate sodium. The mycophenolate sodium formulation is now not recommended in the UK as an initial treatment to prevent organ rejection in adults receiving a kidney transplant. Mycophenolate mofetil is broken down in the liver to form first the active drug mycophenolic acid (MPA), and then the inactive compound mycophenolic acid glucuronide (MPAG). Cells in the body turn some of the MPAG back into MPA.
Concentrations of MPA in the blood rise when MPA is first formed and then again when some of it is re-formed. Most MPAG, and small amounts of MPA, are removed from the body in the urine.
Doctors typically give a standard dose of mycophenolate and then monitor its effect by checking the patient’s medical condition. Most immunosuppressants must be maintained within a narrow therapeutic range. If the concentration is too low, organ rejection may occur; if it is too high, then the patient may develop toxicity. However, the therapeutic range for MPA has not yet been definitively established and doctors can manage most patients without the need to measure the concentration of the drug. When the doctor chooses to monitor MPA levels, the MPA blood test is usually measured as a “trough” level and correlated to clinical side effects. The ‘trough’ level is collected just before the next dose when the drug is at its lowest concentration in the blood.
How is it used?
The mycophenolic acid (MPA) test is requested to measure the amount of drug in the blood. Unlike other immunosuppressant drugs, the therapeutic range for MPA has not yet been definitively established, and the doctor may request levels to monitor drug interactions with other immunosuppressants in combination therapy or to correlate with clinical symptoms and side effects.
Since MPA can lower white blood cell counts and cause anaemia, an FBC (full blood count) will frequently be requested with the MPA test to evaluate the body’s blood cell status. Other tests may also be requested at intervals to check organ function as MPA concentrations can be affected by changes in kidney and liver function. For additional information on how measurement of drug concentrations is used, see Therapeutic Drug Monitoring.
When is it requested?
Mycophenolic acid (MPA) tests may be requested frequently at the start of treatment and then at intervals for as long as the patient is taking mycophenolate. The MPA test may be performed whenever there is a change in dose, a change in other medications that the patient is taking, or whenever a patient has symptoms that suggest side effects, toxicity, or organ rejection. FBC will also be requested weekly for the first four weeks, then twice a month for two months and monthly thereafter for the first year.
Some side effects and symptoms of toxicity may include:
- Anaemia and other blood disorders
- Alopecia (hair loss)
- Nausea, vomiting
- Infections, such as urinary tract and upper respiratory
- Sleeplessness (insomnia)
- Weakness, fatigue
- Muscle pain
- Stomach pain or swelling
- Black or tarry stools, blood in the stools
- Swelling of the hands and/or feet
If any of the above become severe or persistent, the doctor should be notified and he/she may wish to check the level of the drug.
What does the test result mean?
A mycophenolic acid level that is too high may cause toxicity. A level that is too low may lead to rejection of the transplanted organ. Since the therapeutic range is not yet fully established, doctors will often rely on the patient’s clinical signs and their own expertise in addition to drug levels to help guide treatment and adjust dosage if necessary.
Monitoring blood levels can help establish the range in which mycophenolic acid works best for an individual person (i.e. individualise therapy). The level at which the person has minimal side effects while not rejecting the organ is the target level for that individual. If other immunosuppressant and/or other drugs are added, or illnesses occur, the doctor can adjust the dose of mycophenolic acid if necessary until the level is right for a particular individual.
Is there anything else I should know?
Mycophenolic acid (MPA) concentrations can be affected by other medications. Drugs that reduce MPA concentrations include antacids. Drugs that can increase MPA include ganciclovir, probenecid, and aciclovir. Herbal supplements such as Echinacea, and St. John’s wort should be avoided while taking mycophenolate.
MPA can decrease the effectiveness of oral contraceptives, and has been linked with first trimester miscarriages and congenital birth defects. Women should not become pregnant while taking mycophenolate and should not breastfeed. Two forms of birth control are recommended, as is a pregnancy test prior to the start of the medication. Patients who become pregnant should talk to their doctor about the associated risks. Available clinical evidence does not indicate an increased risk of malformations or miscarriage in pregnancies where the father was taking mycophenolate medicines, however mycophenolate mofetil and mycophenolic acid are genotoxic and a risk cannot be fully excluded (British National Formulary, 2018).
Patients taking mycophenolate may be more sensitive to the harmful effects of sunlight, and as a result be at a higher risk of skin cancer. Sun cream protection (SPF 15 or greater) is recommended.
Those who are taking mycophenolate should talk to their doctor before getting any vaccines as they may increase the risk of generalised infection.
Patients may have side effects and experience complications such as infections and slow healing even when taking mycophenolate properly. Like other immunosuppressant agents, MPA is associated with an increased risk of infection and of the development of lymphoma.
How long will I need to be on mycophenolate?
Typically, mycophenolate is given for a long period of time but it will depend on your condition and how you respond to the drug. Mycophenolate is one choice in a range of drugs that may be used to help treat your condition. If you are a transplant patient you must take an immunosuppressant (or combination of drugs) throughout your life. If you are a patient with an autoimmune disorder then you will be prescribed medications to help limit damage to your body and to alleviate symptoms. Talk to your doctor about the best choices for your condition. These choices may change over time.
Where are mycophenolic acid tests performed?
Mycophenolic acid tests may be performed in a local hospital laboratory, but will frequently be sent to a reference laboratory. Because different laboratories use different methods your doctor will usually send your tests consistently to one laboratory for testing.
Should I tell my other health care providers that I am taking mycophenolate?
Yes, this is important information for them, partially because of drug interactions and partially because of the immunosuppressant action of mycophenolic acid. It can affect your ability to heal, to receive vaccinations, and may increase the risk of developing certain cancers (such as skin cancers and lymphoma).