Anyone on Kalydeco seen changes in LFT's?

[dasjsmum]

I know there were a couple of people who were taken out of the trial due to increase LFT. They seem to think that those people may have had predisposition to liver illness.

My son's LFT's improved during the trial and remain normal. He's now been on K for 2.5 years (?) must be around that long I think.

 

[dasjsmum]

I know there were a couple of people who were taken out of the trial due to increase LFT. They seem to think that those people may have had predisposition to liver illness.

My son's LFT's improved during the trial and remain normal. He's now been on K for 2.5 years (?) must be around that long I think.

 

[knobby]

From the prescription information (http://pi.lilly.com/us/cymbalta-pi.pdf), it looks like Kalydeco had a very similar LFT profile when compared to the those on the placebo. Based on the info below, it would appear the compound is extremely safe and has a very low risk of having an impact on your LFTs.

Laboratory Abnormalities
Transaminase Elevations: During 48-week, placebo-controlled clinical studies, the incidence of maximum transaminase (ALT or AST) >8, >5 or >3 x ULN
was 2%, 3% and 6% in KALYDECO-treated patients and 2%, 2% and 8% in placebo-treated patients, respectively. Two patients (2%) on placebo and 1
patient (0.5 %) on KALYDECO permanently discontinued treatment for elevated transaminases, all >8x ULN. Two patients treated with KALYDECO were
reported to have serious adverse reactions of elevated liver transaminases compared to none on placebo [see Warnings and Precautions (5.1)].

Reference: http://pi.lilly.com/us/cymbalta-pi.pdf

 

[Havoc]

In a relatively short term study, yes it would seem to infer that. Unfortunately, people will be on Kalydeco for the rest of their lives (given that something better doesn't come along) and we have no data on long term side effects.

 

[saveferris2009]

<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>Havoc</b></i> In a relatively short term study, yes it would seem to infer that. Unfortunately, people will be on Kalydeco for the rest of their lives (given that something better doesn't come along) and we have no data on long term side effects.</end quote>

This is true. Rarely do you see clinical trials in CF that last longer than 1 year - so with each medication we take, this is the case.... we don't know long term consequences.
Even more so with CF, we use medications off label that haven't been studied at all or in large populations or in our population at all. Or we take higher doses that haven't been studied over long periods of time.
Even non-CF drugs often aren't studied over multiple years. That's the nature of clinical trials - they are costly and when you are dealing with a deadly disease like CF, the goal is to get a promising med to patients as soon as possible.

 

[saveferris2009]

<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>knobby</b></i> From the prescription information (http://pi.lilly.com/us/cymbalta-pi.pdf), it looks like Kalydeco had a very similar LFT profile when compared to the those on the placebo. Based on the info below, it would appear the compound is extremely safe and has a very low risk of having an impact on your LFTs. Laboratory Abnormalities Transaminase Elevations: During 48-week, placebo-controlled clinical studies, the incidence of maximum transaminase (ALT or AST) >8, >5 or >3 x ULN was 2%, 3% and 6% in KALYDECO-treated patients and 2%, 2% and 8% in placebo-treated patients, respectively. Two patients (2%) on placebo and 1 patient (0.5 %) on KALYDECO permanently discontinued treatment for elevated transaminases, all >8x ULN. Two patients treated with KALYDECO were reported to have serious adverse reactions of elevated liver transaminases compared to none on placebo [see Warnings and Precautions (5.1)]. Reference: http://pi.lilly.com/us/cymbalta-pi.pdf</end quote>

Cymbalta?!

 

[dasjsmum]

Well, as I said, my son is one of the few people in the world who actually has been on Kaly for nearly three years. His LFT improved on Kaly and he has had NO side effects at all, major or minor.

There's another young girl we know of (in our Aus FB Kaly group) who has been on Kaly for the same length of time as my son Donovan (both were on the real drug, not placebo during Ph3), and she has also had no adverse effects on her liver or other wise. The open label trial is the best indicator we have of long term side effects, and so far there have been none.

There were a couple of people who expereinced some adverse liver events during the trial, but there is NO EVIDENCE that Kaly is toxic to the liver or to any other organs, in fact the opposite is true, it has improved the function of Donovan's liver, lungs and pancreas/digestive system.

 

[saveferris2009]

I still don't understand why knobby posted links to Cymbalta

 

[Havoc]

<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>dasjsmum</b></i> Well, as I said, my son is one of the few people in the world who actually has been on Kaly for nearly three years. His LFT improved on Kaly and he has had NO side effects at all, major or minor. There's another young girl we know of (in our Aus FB Kaly group) who has been on Kaly for the same length of time as my son Donovan (both were on the real drug, not placebo during Ph3), and she has also had no adverse effects on her liver or other wise. The open label trial is the best indicator we have of long term side effects, and so far there have been none. There were a couple of people who expereinced some adverse liver events during the trial, but there is NO EVIDENCE that Kaly is toxic to the liver or to any other organs, in fact the opposite is true, it has improved the function of Donovan's liver, lungs and pancreas/digestive system.</end quote>

Well if you look at the MSDS for the active ingredient this is what you find:
<pre>Code letter and hazard designation of product: Hazard-determining components of labeling: EU Risk And Safety phrases: ? S24/25: Avoid contact with skin and eyes ? S26: In case of contact with eyes, rinse immediately with plenty of water and seek medical advice ? S28: After contact with skin, wash immediately with plenty of water ? S36/37/39: Wear protective clothing, gloves and eye/face protection ? R28: Very toxic if swallowed ? R38: Irritating to skin ? R41: Risk of serious damages to eyes ? R48: Toxic; danger of serious damage to health by prolonged exposure ? R62: Possible risk of impaired fertility ? R63: Possible risk of harm to unborn child</pre>
<pre></pre>
<pre>Source: http://www.drugbank.ca/system/msds/DB08820.pdf?1330108464 </pre>

 

[knobby]

Saveferris, sorry about the bad link! I have no idea what Cymbalta even is. The appropriate link is http://pi.vrtx.com/files/uspi_ivacaftor.pdf

Havoc, the MSDS has this for the Kalydeco from the link you sent:
11. TOXICOLOGICAL INFORMATION:
RTECS#:
? Acute toxicity: none known
? Primary irritant effect: not known
? On the skin: none known
? On the eye: not known; may be an irritant

 

[Incomudrox]

<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>knobby</b></i> Saveferris, sorry about the bad link! I have no idea what Cymbalta even is. The appropriate link is http://pi.vrtx.com/files/uspi_ivacaftor.pdf Havoc, the MSDS has this for the Kalydeco from the link you sent: 11. TOXICOLOGICAL INFORMATION: RTECS#: ? Acute toxicity: none known ? Primary irritant effect: not known ? On the skin: none known ? On the eye: not known; may be an irritant</end quote>

Did you miss the part about prolonged exposure causing seriouse health implications or did you just not want to see it?

Just because they don't know the exact mechanism of toxicity, doesn't mean it isn't toxic.

 

[dasjsmum]

All drugs carry risks for some people. You're all aware that the antibiotics used for CF are extremely toxic...Tobramicin causes deafness and can cause kidney failure, as can Cipro and and other drugs you all take all the time. The only indicater we have of potential toxicity over time is via the people in the Open lable trial. Our experience has been completely positive, so hopefully that will be the outcome for the majority of others too. As there are now such a large group of people taking Kaly it will be interesting to see the percentage of people who do experience some adverse affects over time. If Donovan hadnt been on Kaly for the last three (almost I think) years he would definitely be experiencing some pretty adverse effects now from declining lung function! Kaly has given him a normal life and I cant wait for everyone with cf to be able to experience the same level of wellness he now has. He is having a normal life! He is never sick. He's 32, working full time, playing soccer, paintball, doing everything. It's fantastic and I hope all you and my other kids can get onto it or the combined drugs asap.

Sorry Jonathan, what's the MSDS? that does sound pretty bad, but really we can only go off the long term Open Label. So far it's looking really great (in our experience anyhow). I only know one other person whose been on the drug since the beginning of the Ph3 (and things are going great for them too - she's only 9 I think) and Lauren who was on placebo to start with. It would be very interesting to hear others experiences though.

 

[Incomudrox]

MSDS is Material Safety Data Sheet. There is a MSDS for every chemical hazardous or not. Sure Tobramycin/Gentamicin (Aminoglycosides) and Colistin (Polymyxin) cause problems, but uhh they cause problems and we only take them IV for 2-3 weeks maybe 3-4 times a year for the average CFer. If you're on Kalydeco its everyday for the rest of your life....

 

[dasjsmum]

Thanks for that info <img src="i/expressions/face-icon-small-smile.gif" border="0"> You're right with the every day for the rest of your life comment, and we will have to see how it goes long term. I guess you could take it for a year and have six months off etc., (but I cant imagine anyone wanting to do that once they experience the difference it makes).

I've also heard that apparently it isnt considered dangerous to the fetos if pregnant and some people may be considering using Kaly while pregnant.