Reduction of Kalydeco®

Question

Dear Expert Advisory Team,
I would appreciate your opinion on the following matter: based on several sweat tests conducted while I was taking Kaftrio/Kalydeco®—which consistently yielded results between 10 and 18 mmol/L (a very low value)—my CF clinic is now considering whether, in my case, "less might actually be more." The conclusion reached was that I should take one tablet of Kaftrio® in the morning and one in the evening, while omitting the Kalydeco® entirely. I should mention that I experience absolutely no side effects at my current standard dosage, which I have now been taking for five and a half years.
Given that I suffer no side effects and the medication works so effectively for me, I feel quite apprehensive about this little "experiment." I did attempt to reduce the dosage on a trial basis recently, but I immediately developed "cold-like symptoms" shortly thereafter. Of course, it has not been conclusively determined whether these symptoms were causally linked to the dosage reduction. My current plan—which has also been discussed with the clinic physicians—is as follows: to attempt another dosage reduction shortly before my next scheduled clinic visit. I was told that reducing the dosage (specifically, discontinuing the Kalydeco®) one week prior to the appointment would be sufficient to obtain a valid sweat test result.
Now, here is my question to you: Is this approach—or the rationale behind it—considered standard practice? Is there any existing clinical experience regarding this specific scenario? What arguments would support such a reduction, and what arguments would weigh against it?
Many thanks, UE (CF, female, 54 years old, FEV1 68)

Answer

Dear inquirer,
You would like to know whether it is possible to reduce your dosage of Kaftrio® and Kalydeco® without compromising the efficacy of the medications. You report that you tolerate the full dosage well and that, while undergoing this therapy, your sweat test results fall within the normal range. You have noted a temporal correlation between a brief period of dosage reduction and the onset of cold symptoms.
As a general rule, a medication's dosage can—and indeed should—be individually adjusted based on its therapeutic effect and any potential side effects. However, this process should always be undertaken in close consultation with your treating physician and under medical supervision. We do not recommend independently altering the prescribed dosage.
Before considering a dosage reduction for Kaftrio® and Kalydeco®, it is advisable to conduct a thorough assessment of the therapy's current efficacy. This assessment should address, for example:
• To what extent have your sweat test results improved?
• How has your lung function evolved?
• Has your susceptibility to infections changed?
Ideally, these parameters should be re-evaluated shortly before any planned dosage adjustment. Additionally, it may be helpful to measure the concentration of the medication in your bloodstream. Such blood level testing can be arranged, for instance, through the Munich Cystic Fibrosis Center (Department of Pneumology), LMU University Hospital / City Center Campus, Ziemssenstraße 1, 80336 Munich.
As a next step, a reduced dosage can be trialed for a specific period (e.g., 4 to 8 weeks). At the conclusion of this phase, the same diagnostic assessments should be repeated—ideally, once again including a measurement of blood medication levels. This approach enables your physician to evaluate how the dosage adjustment affects your condition and to determine whether the therapy remains sufficiently effective.
Regarding your final question: A change in dosage implemented shortly before a follow-up sweat test can indeed influence the results. In fact, even an adjustment made just one day prior to the test can produce measurable differences.
Sincerely,
Dr. med. Christina Smaczny

17.05.2026