Possible Causes & What You Can Do If You Are Experiencing Kaftrio Side Effects

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Coughy and Creon

5 min readFeb 12, 2021

Adverse reactions associated with Kaftrio/Trikafta have been the hot topic of conversation among the global CF community recently. As more and more patients use the superhuman pills, many are experiencing neurological and mental health side effects that were not listed from the trial data.

I share about my own Kaftrio/Trikafta experiences including a comprehensive list of side effects and, why I need to temporarily stop the drug after 4 months due to adverse reactions, here.

Possible Causes For Kaftrio Side Effects

Hormones

There is a strong possibility Kaftrio/Trikafta interacts with hormones so my team are working closely with the endocrinology department to look at what hormones are doing — everything from estrogen to thyroid function and more.

Why? Well, most of the side effects can easily be hormonally induced and as we know, at my cf centre, almost all patients who have reported the cognitive issues associated to Kaftrio/Trikafta have been female.

Some patients have reported lactating breasts and changes to their menstrual cycles which again can only be attributed to hormonal changes. There have been other instances where patients who did wonderful on Kaftrio/Trikafta whilst pregnant but then developed a flurry of side effects after giving birth.

CFTR-protein in the brain

We know the CFTR protein exists in the brain however we have little evidence of what it will do once activated. As most of the unlisted side effects are cognitive based, there are possibilities it is attributed to Kaftrio/Trikafta activating the CFTR protein in the brain.

Speculation also sits around what other dormant proteins are being switched on by Kaftrio/Trikafta that we are not aware about, in some patients.

Changes to neurotransmitters

A study carried out in 2018 by Schneider, identified that ivacaftor caused changes to brain chemicals such as serotonin and dopamine.

In standard individuals this would usually stimulate the pathways in the brain and increase the supply of happy hormones to overall have a positive effect.

Yet, in some patients it was having an opposite effect causing an onset of depression, anxiety and other mental disorders. Why this happens it is not yet fully understood. Having a predisposition to mental health disorders before starting the drug could be one factor in them developing.

Dosing issues

During the Vertex trails multiple doses were tried and tested. Eventually two doses were thought to be optimal for safety alongside giving superior improvements to the CFTR proteins. The lower of those two doses were chosen for FDA licencing.

Unfortunately, clinical trails rarely mirror what goes on inside the actual clinical room, this is often why many side effects are not initially identified in the trials. Our bodies are all individually unique so some patients may need something as small as a dosing alteration to manage the side effects they are experiencing.

At no point is any of this based of evidential findings unless stated otherwise.

Speaking To Your CF Team About Side Effects

The first port of call is discussing concerns with your cf team, sadly I know many cf patients in the UK have felt their side effects aren’t being acknowledged.

In this instance, I urge to report elsewhere and show your cf team evidence of other cf patients who have reported the same issues.

You can forward evidence of trials that support your concerns — this clinical trial identifies that Trikafta can cause psychological issues in some patients and that all cf teams should take reports of neurological side effects into account.

Lastly, ask your team to liaise with a different cf center who are investigating the issues, for a second opinion.

Other Things To Do If You Are Experiencing Side Effects

You know that old saying: Knowledge is power? It is true.

Reporting our experiences is the only way we can eventually get these side effects listed which will create a gateway for people who are experiencing them to be acknowledged by all medical professionals as well as identify ways to manage the adverse reactions.

Here is what you can do if you are experiencing side effects too:

Report to the Yellow Card scheme (UK)

You can log your side effects to the yellow card scheme here.

The Yellow Card scheme is run by the MHRA and is the UK system for collecting and monitoring information on suspected side effects or adverse incidents involving medicines.

Report to the FDA (US)

You can log your side effects to the FDA here.

The FDA licence all drugs in the US. Voluntary reporting can help FDA identify an unknown risk for approved medical products.

Report directly to Vertex Pharmaceuticals

You can contact Vertex Pharmaceuticals here.

We have a duty to ourselves and others to report any new side effects to the pharmaceutical companies that make the medicine — this can ensure it is logged and investigated correctly.

Mentally Coping With Side Effects

Connect with others in the community to feel less alone

Dealing with the adverse effects of Kaftrio/Trikafta can be tough both physically, mentally and emotionally — if you are suffering, know you are not alone. Reach out.

A non-judgmental, private Facebook support group for people struggling with adverse side effects or for people who have been taken off the modulating drugs can be found here.

Don’t feel guilty, responsible or like your experience isn’t valid

I struggled with all of the above. It isn’t your fault these side effects are happening, you aren’t doing anything wrong. This is not a lack of gratitude. You are not letting yourself or other people down. What you are experiencing is valid and you deserve to be heard and supported.

Avoid giving up all hope

I think what is most daunting is not knowing what the future holds and that feels heightened when dealing with modulating drugs. Speak to your team psychologist if you feel it will help deal with how you are feeling about stopping modulators. Most importantly, don’t give up.

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