I realize the Phase 2 CT for Nilotinib has gotten some very positive reviews on this forum, but just be aware of some of the serious downside with this drug.
My first point should be obvious to anyone who has thoroughly read the results of the CT conference presentation or you can scroll down the comments started on that HU thread to see the word "palpitations". I would say the word arrhythmias is the accurate term to use.
#1 This drug (regardless of its name) prolongs the QT interval with the possibility of sudden death, especially those individuals with a long QT syndrome (LQTS) which is a disorder of the heart and its electrical impulses. I would assume it is also problematic for those who do not exhibit LQTS. Very probable.
#2 If you insist on using this drug, avoid use of concomitant drugs known to prolong the QT interval and as well as CYP3A4 inhibitors classified as "strong" (not typical of PD treatment protocols, but you never know).
#3 Regular and consistent EKGs and blood work is advisable to monitor the QT problem that might be created with this drug.
If you do decide to use this drug, please understand the possible consequences.
Sharon
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sharoncrayn
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Sharon's advice is well taken. I believe i've mentioned Tasigna's black box designation, the QT interval and need for monitoring. Check out her academic credentials under her profile in HU and you will realize that she speaks with some authority.
It is a shame that this genre/class of drugs, which can benefit PD patients who have had PD for some time, comes with some serious downside risks, not the least of which is the issue of QT levels. Low blood counts are a very distinct possibility in the older cohorts. Ad in decreased blood flow and pancreatic issues. You are dealing with a serious complexity of multiple issues.
Bottom line?...Powerful class of drugs which should be used only under constant monitoring by a qualified physician who understands the pros and cons. Not many do unless they have prescribed it before and understand what can happen.
As to this Phase 2, once again, I see the need for extending these CTs for a sufficient time period to determine the longer term impact on patients. These short term "placebo" trials simply aren't the answer even if a drug is "repurposed". I realize this approach goes against my call for "fast tracking" these drugs whenever possible, but we already have an extensive set of data on the impact of Tasigna. It is very clear to anyone what the issues are with this drug. Or it should be.
We use this class of drugs as chemotherapeutics in vet medicine (as I believe you do in human med). I've seen some major side effects and sick animals. Yes they are still safer than some of the older cancer drugs but still.
Sharon, does it make a difference that the dose used for the most recent PD study with Nilotinib is 150 mg once daily, versus 600-800 mg daily for its current labeled indication? Might that lower dose serve to mitigate the risk?
If you noticed in the Phase 2 CT, their final analysis indicated that they recommended going with 150 rather than the 300 that was also given to one of the 3 cohorts. So, this decision might imply that they were cognizant that the higher the dose the higher the probability of side effects,, and vice versa. Although they might have also seen equal (or nearly equal) benefits for both the 150 and 300 and sided with caution.
In Tasigna's case, the recommendation is 300x2 per day or 600, or even 800 as you noted. But this dose schedule is for CML (serious blood cancer) patients who can "tolerate" the 600-800 level....assuming no serious liver problems or other disease. Many can't tolerate it.
Furthermore, we don't have stats on what dose level caused QT sudden death and other issues that required cessation. We can assume it was the higher dose levels, but we can't be sure.
So, in some sense, it all depends on how you define "mitigate" and whether or not PD patients ultimately need to escalate their dose over time a la sinement or modopar.
My answer is that the 150 is obviously less harsh than 600-800 assuming the individual has no liver problems, low blood level problems, decreased blood flow, or long QT problems. But what about 2-3 years down the road? Will these issues develop? Will the individual go in for regular EKGs and blood work to make sure everything is OK?
My answer is that is that it is certainly likely in the older cohort, which is mainly PD, that these problems will surface with continued use of this drug because 150 won't suffice over time. Let's be realistic here.
Just my observations coordinating 2 PD support groups for the last 10 years where it is typical for individuals to increase their PD meds; not to decrease them or keep them stable.
I wonder if the dose amounts of Tasigna black box would change if being prescribed for PD instead of Leukemia I understand that dose amounts for leukemia are much higher. Probably have to wait and see.
I am somewhat incredulous that with the thousands of people being treated with Tagsigna and the elapsed time since it was approved by the FDA (2007) of twelve years. . . that we haven't accumulated some good information on the relationship of dosing to serious side effects. You have raised a number of important considerations for those people considering taking this drug, the need for monitoring QT interval, blood tests etc.
You have brought up "black box" and "sudden death" but you have provided no information regarding the likelyhood that these things would or have occurred for many people who are currently taking the drug. As one of the most technically qualified people to comment on this, it would be a great service to us all if you could provide some information in this regard.
The real world is the real world, not an "ideal" world. You are asking for information that doesn't exist anywhere.
Novartis has refused to provide information on adverse events with this drug because the US/FDA has no reliable "adverse event" national database that requires drug companies and physicians to report adverse events. So, I an unable to comment on what is really the problem by dose, age, gender, etc. in terms of adverse events.
Novartis is the drug maker for Tasigna. They have done their best to conceal any adverse events due to this dug because they made about $2 BILLION on this drug each of the last 3-4 years. Most of this revenue coming from the North America.
We know anecdotally Tasigna creates many problems (already outlined by me) including other forms of cancer besides ML, as well as severe atherosclerosis almost "immediately" upon dosing regardless of previous QT problems.
Novartis knew these problems existed with Tasigna as far back as 2011. So these adverse events are nothing new with this drug.
Proceed with extreme caution if you insist on taking this drug or its cousins.
I have been a do-it-yourself Nilotinib users since November 1, 2016.
Novartis is currently defending lawsuits that long-term use causes atherosclerosis.
Fortunately, 1) I am a hypochondriac and 2) get my healthcare at the Minneapolis VA which provides me with blood panels, EKGs, and anything else I want whenever I ask, which is often, and even so, every doctor I see, which is a lot, tells me they strongly disapprove -- which I know is good advice. The same advice I've often given on this forum.
It's clear it has relieved me of constipation and I only take 5 to 10 Sinemet per week which ain't bad considering I am 10 years in which means I am progressing slowly and I believe some of that is attributable to N.
It's a conundrum. A drug that seems to work, but is dangerous.
I think your position is potentially sensible and not reckless, given the current available evidence.
It's very easy for someone that doesn't have PD to advise against taking a drug with known side effects. It's not quite so easy to watch your PD relentlessly progress.
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What PwP need is regular rigorous exercise motivations NOT more levadopa
Improving the Bio-availability of Levodopa
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