Cyclosporine

Tests for cyclosporine are used to measure the amount of this drug in the blood to determine whether cyclosporine concentrations have reached therapeutic levels and are not in a toxic range. Cyclosporine is a drug that diminishes the body’s immune response. It is prescribed for organ transplant recipients to prevent organ rejection and for some people with autoimmune conditions, such as rheumatoid arthritis or psoriasis, to alleviate symptoms.

It is important to monitor levels of the drug for several reasons:

• There is not a good correlation, as with some other medications, between the dose of cyclosporine given and level of drug in the blood.
• Absorption and metabolism of oral doses of cyclosporine can vary greatly between people and even in the same person depending on the time of dose and what food is eaten.
• There can be variation in blood levels due to the brand or preparation of cyclosporine prescribed.
• In transplant patients, it is particularly important for graft survival to ensure that cyclosporine levels are high enough immediately following surgery to prevent rejection of the transplanted organ.
• In the case of rheumatoid arthritis or psoriasis, blood levels of cyclosporine must be high enough to give relief of symptoms.
• In the case of kidney transplantation, blood levels may help to distinguish between kidney rejection and kidney damage due to high levels of cyclosporine.
• Cyclosporine is associated with several toxic side effects that can be avoided if blood levels are monitored. The dose may be adjusted if the detected level is too high.

By monitoring cyclosporine blood levels, healthcare practitioners can better ensure that each individual is receiving the right amount and formulation of drug needed to treat his or her particular case, to maximize the therapeutic effects while minimizing the drug toxicity.

Cyclosporine testing is ordered frequently at the start of therapy, often on a daily basis when trying to establish a dosing regimen. Once an appropriate dose has been determined, the level can be tested less frequently and may eventually be tested monthly, once every two months, or at longer intervals. However, testing may be done more often when a person becomes ill or begins taking additional medications that may affect the metabolism of cyclosporine. A change in a person’s metabolic status may also prompt more frequent testing.

Often in transplantation, people will begin with higher doses of cyclosporine at the start of therapy and then decrease the dose over the course of long-term therapy. In the cases of rheumatoid arthritis or psoriasis, if a person appears to tolerate the drug well, the dose may be increased to further improve symptoms.

With each change in dose, blood levels need to be measured. In addition, the frequency of testing depends on a number of factors, including the medical reason for taking cyclosporine. In organ transplantation, the type of organ transplanted and the recipient’s age and general health status will inform dosing. For example, a person with a transplanted liver may need to be monitored more often since cyclosporine is metabolized mainly by the liver and impaired function can slow clearance of cyclosporine from the blood.

When organ rejection or kidney toxicity is suspected, tests may also be ordered more often. Some signs and symptoms of cyclosporine toxicity are:

• Kidney damage (nephrotoxicity)
• High blood pressure
• Tremors
• Bleeding, swelling, overgrowth of gums (gingival hyperplasia)
• Excess hair on the body and face (hirsutism)
• High lipid levels in the blood (hyperlipidemia)
• Infections
• Abnormal blood test results on a complete blood count (CBC)
• Low blood magnesium level
• High blood potassium level
• Liver damage (hepatotoxicity) that may cause jaundice, including yellow eyes, dark urine and/or pale stools
• Diarrhea
• Nausea

The therapeutic range for cyclosporine depends on the method used to measure the drug, the type of transplant, and the length of time since the transplant. Results obtained from different types of samples and different methods are not interchangeable. Healthcare practitioners will be guided by the laboratory as to the appropriate therapeutic range to apply to a specific person’s test result.

If trough levels fall below the desired range, there is a risk of transplant rejection or symptom recurrence. If levels detected are above the range, there is a risk of toxic side effects.

Peak concentrations of cyclosporine in samples collected 2 hours post-dose are sometimes tested in transplant cases. High levels of cyclosporine in peak samples are correlated with reduced rejection rates, especially in the first year after transplant surgery.

A majority of laboratories use whole blood samples for cyclosporine testing instead of serum or plasma and will collect samples 12 hours after the last dose or just before the next dose (trough levels).

Some laboratory methods are more specific for the cyclosporine parent drug, while others measure the parent drug plus the metabolites, so their respective ranges will differ. Because cyclosporine therapeutic ranges can vary with type of assay performed by the laboratory, it is recommended that blood samples be tested by the same institution over the course of therapy. Results will be more consistent and will correlate better with the reported therapeutic range.

For conditions other than transplants, cyclosporine may be prescribed with other medications, such as non-steroidal anti-inflammatory drugs (NSAIDs). In transplant cases, other anti-rejection drugs may be used along with cyclosporine. These drugs will work in conjunction to treat a person’s condition. In addition, cyclosporine blood levels can be affected (either increased or decreased) by other medications a person may be taking. It is important for health practitioners to be are aware of what medications and supplements their patients are taking and to be notified of changes in diet or health status that may affect cyclosporine concentrations.

Several prescription drugs can interact dangerously with cyclosporine and should not be taken at the same time. Tell your health care provider about all the medications you are taking.

Cyclosporine may cause high blood pressure and kidney damage. Tell your health care provider if you have or have ever had high blood pressure or kidney disease. Healthcare practitioners may order additional laboratory tests to detect high lipid levels or to monitor kidney and liver function.

Avoid grapefruit juice. It slows the body’s normal breakdown of cyclosporine, allowing it to build up to potentially excessive levels in the blood, and can maintain this effect in the body for three days or more following the last glass of juice.

Magnesium clearance is enhanced by cyclosporine, possibly leading to symptoms related to low blood magnesium. A healthcare practitioner may monitor magnesium levels and treat with supplements as required. High blood potassium sometimes occurs. A healthcare practitioner may monitor potassium levels and will use caution with potassium-sparing diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, potassium-containing drugs, and potassium-rich diets.

If you are a transplant recipient, you generally will stay on cyclosporine as long as that is the treatment of choice for you. If there are signs of rejection, even with blood levels in the therapeutic range, you may be switched to a different immunosuppressant drug. Also, there is a greater chance of toxic side effects the longer you are on cyclosporine, so a healthcare practitioner may choose to alter drug therapy when you have been on cyclosporine for more than 2-3 years.

If you have an autoimmune disorder such as rheumatoid arthritis, Crohn disease, or psoriasis, you will be treated with cyclosporine only when your symptoms are acute and if other treatments have not been effective. It is not advised that your stay on cyclosporine for more than a year due to an increase in the likelihood of toxic symptoms the longer you are on the medication. Short-term or intermittent courses of 12 weeks at a time are more advisable.

Cyclosporine will usually be monitored by healthcare practitioners who have specific knowledge of the condition or disease for which the drug is prescribed. They tend to be very familiar with cyclosporine and its use in therapy, and they understand the importance of monitoring the drug. They may include your surgeon or doctor treating you for your arthritis or psoriasis.