Ciclosporin

How is it used?
When is the test requested?
How is the test result interpreted?
Is there anything else I should know?

How is it used?
Testing ciclosporin helps ensure that its concentration is high enough to be effective but not so high as to be toxic. There are many reasons to measure ciclosporin concentrations:

• There is poor correlation between the dose given and the concentration found in the blood.
• Absorption and metabolism of oral ciclosporin vary from person to person, and in the same person depending on the timing of doses and food eaten.
• Blood concentrations vary depending on the manufacturer and formulation of the medicine.
• In transplant patients it is important that the ciclosporin concentration is high immediately after the operation to prevent rejection.
• In rheumatoid arthritis or psoriasis, the blood concentration of the medicine must be high enough to start having a beneficial effect on symptoms.
• After a kidney transplant, it helps distinguish kidney rejection from drug-induced kidney damage.
• Ciclosporin is associated with serious side effects that can be avoided by monitoring its concentration

Monitoring with this test therefore helps ensure that the patient receives the right dose of the medicine.

When is the test requested?
At the start of treatment it is done daily to find the right dose, then once every two or three months. It is done more often when the patient falls ill or starts taking medicines that interact with ciclosporin metabolism. Any change in the patient’s metabolism is followed by more frequent monitoring.
In transplant patients the ciclosporin dose is often high immediately after the operation and is then reduced for long-term treatment. In rheumatoid arthritis or psoriasis, if the patient tolerates the medicine the dose may be increased until symptoms improve. Ciclosporin in the blood must be measured after every change of dose. How often the test is done also depends on many factors, including the type of organ transplanted and the patient’s age and general condition. For example, a patient who has had a liver transplant must be monitored more often, because ciclosporin is metabolised by the liver itself. The test is done more often when rejection or kidney toxicity is suspected.
Some symptoms of ciclosporin toxicity are:

• Kidney damage
• High blood pressure
• Tremors
• Bleeding and swollen gums
• Hirsutism
• Hyperlipidaemia

How is the test result interpreted?
The therapeutic range of ciclosporin depends on the method used to measure it, the type of transplant and how long ago the transplant took place. Doctors generally prescribe high doses of the medicine immediately after the transplant and then reduce them over time so that the patient remains stable. Results obtained from different samples and with different methods are not comparable, so the laboratory must guide the doctor in choosing the dose to give.
If ciclosporin levels in the blood are below the therapeutic range, the patient is at risk of rejecting the transplanted organ or of symptoms returning; if they are above it, there is a risk of side effects or toxicity.
Peak blood concentration occurs two hours after a dose. High peak ciclosporin levels are linked to a lower risk of rejection, particularly during the first year after the transplant.

Is there anything else I should know?
Most laboratories test whole blood collected twelve hours after the last dose or just before the next. Some laboratories specialise in measuring molecules similar to ciclosporin, while others measure the metabolites of the medicine, so reference values may differ. Since ciclosporin measurements vary with the method used, it is important always to have the test at the same centre during treatment.
In conditions other than transplants, ciclosporin may be prescribed together with other medicines, such as non-steroidal anti-inflammatory drugs (NSAIDs). In transplants, ciclosporin is given together with other medicines that also prevent rejection. In addition, ciclosporin blood levels can be changed by other medicines, so it is important that the doctor knows about the patient’s medicines and any changes in diet or health.
Ciclosporin can cause kidney damage, especially at high doses and during long periods of treatment. It can also raise blood fats and cause liver damage, which must be monitored with laboratory tests requested by the doctor

How long is ciclosporin given for?
It depends on the condition being treated and the treatment chosen; if there are signs of organ rejection or toxicity, or two or three years have passed since treatment began, the treatment is usually changed.

Patients with autoimmune diseases (rheumatoid arthritis, Crohn’s disease, psoriasis and others) are treated with ciclosporin only when symptoms are acute or when other medicines have had no effect. It is not advisable to give ciclosporin for more than a year because of its toxic effects; the medicine should instead be given for short periods or intermittently (usually for periods of twelve weeks)

Who requests the test?
Ciclosporin is normally monitored by the specialist who has extensive knowledge of the conditions for which the medicine is prescribed and is familiar with it. These specialists include surgeons and doctors who treat autoimmune diseases (arthritis, psoriasis and others).