Cyclosporin

The test for cyclosporin is ordered to measure the amount of drug in the blood to determine whether drug concentrations have reached therapeutic levels and are not in a toxic range. It is important to monitor levels of cyclosporin for several reasons:

• There is not a good correlation, as with some other medications, between the dose of cyclosporin given and level of drug in the blood.
• Absorption and metabolism of oral doses of cyclosporin can vary greatly between patients and even in the same patient 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 cyclosporin prescribed.
• In transplant patients, it is particularly important for graft survival to ensure that cyclosporin levels are high enough immediately following surgery to prevent rejection of the transplanted organ.
• Blood levels need to be high enough in the case of rheumatoid arthritis or psoriasis to begin 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 cyclosporin.
• Cyclosporin is associated with several toxic side effects that can be avoided if blood levels are monitored and the dose adjusted if the level detected is too high.

By monitoring cyclosporin blood levels, doctors can better ensure that each individual is receiving the right amount and formulation of drug needed to treat their particular case.

Cyclosporin 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 once every 1-2 months.

Often in transplantation, patients will begin with higher doses of cyclosporin 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 patient 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 type of organ transplanted, age and general health status of the patient. For example, a patient with a transplanted liver may need to be monitored more regularly since cyclosporin is metabolised mainly by the liver, and impaired function can slow clearance of cyclosporin from the blood. Tests may also be ordered more often when organ rejection or kidney toxicity is suspected.

The therapeutic range for cyclosporin depends on both the method used to measure the drug and the type of transplant. Results obtained from different types of samples and different methods are not interchangeable. Your doctor will be guided by the laboratory that does the testing as to the appropriate therapeutic range to apply to your test result.

A majority of institutions use whole blood samples 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 cyclosporin parent drug while others measure the parent drug plus the metabolites so their respective ranges will differ.

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.

Some signs or symptoms of cyclosporin toxicity are:

• kidney damage
• high blood pressure
• tremors
• bleeding, swelling, overgrowth of gums
• hirsutism
• hyperlipidaemia

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

Because cyclosporin therapeutic ranges can vary with type of assay performed by the laboratory, it is advised that your 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, cyclosporin 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 cyclosporin. These drugs will work in conjunction to treat your condition. In addition, cyclosporin blood levels can be affected by other medications you may be taking. You should notify the doctor who is monitoring your cyclosporin levels of any additional drugs you are taking.

Cyclosporin can cause damage to the kidneys, especially with higher blood levels and over a longer period of time. Your doctor may want to monitor kidney function tests. Increases in blood lipid levels have been noted in some cases and liver function may be affected in cyclosporin therapy as well. Your doctor may order additional laboratory tests to detect high lipid levels or to see if your liver has been affected.