cyclosporine toxicity

[Roxy]

I posted a while ago about my cyclosporine not stabilizing post transplant and hoping it would soon. Now, I am 10mths post transplant and still no luck! The worst part is that the past month my cyclosporine level rose up to about 300(which is very toxic) and as a result of it not stabilizing and switching between 100 - 300, my creatinine went up to 2.8. Just as we were about to do a biopsy ( in case of rejection) , the creatinine finally started coming down and is now at about 2.1. My baseline is 1.8, so hopefully in the next week I will get back to that. The doctors are thinking it is cyclosporine toxicity and since this has been an on and off thing for the past several months, I have to fly to Seattle this week to see my transplant team and they are going to switch me to Prograf or Rappamune. Is it common to have this much difficulty getting a medication to stabilize?? It makes me worried that when they switch the meds, I'm just going to have the same problem. I don't really know what to think of this other than to just keep going through it and waiting to see what happens.  Blah, just so frustrated I guess 

[Chris]

Sorry to hear about your problem. It does happen to some people that they have a problem taking a certain drug. In my transplant center I have seen some people can't take Prograf while others can't take Rappamune. At my center, cyclosporine, prednisone are a last resort to go to. Hopefully you won't have trouble with your new medication, but be prepared to do some frequent blood test if you haven't been doing that already due to the cyclosporing problem.

[okarol]

That's sounds scary and frustrating. I hope you get a solution soon. The following is from "Lab Tests Online"
You may have already read this info but here's what I found:

Cyclosporine

Also known as: Often referred to by brand name
Formal name: Cyclosporine
Related tests: Therapeutic drug monitoring, BUN, Creatinine, Lipid profile, Liver panel
   
   
The Test
     
How is it used?
When is it ordered?
What does the test result mean?
Is there anything else I should know?

How is it used?
The test for cyclosporine 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 cyclosporine 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 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 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.
# 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 cyclosporine.
# Cyclosporine 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 cyclosporine blood levels, doctors can better ensure that each individual is receiving the right amount and formulation of drug needed to treat their particular case.

When is it ordered?

Cyclosporine 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 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 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 cyclosporine is metabolized mainly by the liver, and impaired function can slow clearance of cyclosporine from the blood. Tests may also be ordered more often when organ rejection or kidney toxicity is suspected.


What does the test result mean?

The therapeutic range for cyclosporine 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 cyclosporine 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 cyclosporine toxicity are:
# kidney damage
# high blood pressure
# tremors
# bleeding, swelling, overgrowth of gums
# hirsutism
# hyperlipidemia

Peak concentrations of 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.


Is there anything else I should know?

Because cyclosporine 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, 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 your condition. In addition, cyclosporine blood levels can be affected by other medications you may be taking. You should notify the doctor who is monitoring your cyclosporine levels of any additional drugs you are taking.

Cyclosporine 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 cyclosporine therapy as well. Your doctor may order additional laboratory tests to detect high lipid levels or to see if your liver has been affected.

Ask the Lab
     
If you still have a question about your test or need help interpreting the results of your test, you can visit the ASCLS web site to complete a lab testing information request form, and a certified clinical laboratory scientist will gladly help you! Your communication will be kept confidential.Go to http://www.ascls.org/labtesting/disclaimer.asp

More about Lab Tests Online http://www.labtestsonline.org/site/index.html

[Sluff]

Sorry to hear about your trouble with the meds Roxy, I was on cyclosporine for 18 months to slow down the protein loss caused by FSGS, obviously I am predialysis. I started having problems also so we removed the cyclosporine and I was somewhat stabilized but lately I've noticed more foamy urine again ( a sign of protein loss) so my assumption is my Neph will put me back on the cyclosporine. I refused the steroid treatment.

Good luck. 

[Rerun]

They need to switch you to Prograf.  It will work beautifully.  Don't worry.  Just get to Seattle ASAP and get on the right medication. 

[willieandwinnie]

Roxy, it's good to hear from you. Sorry your having trouble getting her medications straightened out, Len is 6 months post tx and he is also having trouble with some medications. He's lab numbers were out to lunch and doctor lowered his prograf because of toxicity. I now understand why they say that the first year is the hardest, so many changes. Hang in there Roxy and please keep us posted. 

[stauffenberg]

Many dialysis patients are diabetics with gastroparesis, which delays passage of cyclosporine from the stomach to the intestines and from there to the bloodstream, and this can create extreme irregularities with the cyclosporine levels in the blood.

[willieandwinnie]

stauffenberg, you should be IHD resident doctor. 

[KT0930]

I've had similar problems with prograf. My levels have not become toxic, but they are not very stable, either. It had been between 9.0 and 12.5, but then dropped to 7.4, so now they've upped my dose, and I have to go back this week for labs. My point is, yes, this happens with other meds as well, and really just depends on how your body absorbs or reacts to a med, like Stauff said.

Either way, I'd much rather deal with the uncertainty of prograf than the side effects I had with cyclosporine with my last transplant!

[Sluff]

stauffenberg, you should be IHD resident doctor.

I assumed he already was.   

[Roxy]

Thank you guys for your kind words and information. I leave tomorrow morning for seattle, so hopefully after this weekend things will be looking up. I think my biggest worry is that I've already lost some kidney function on a kidney that wasn't working 100% to begin with. Oh well, guess I'll just have to wait and see a little longer to see if things get better.