7 replies to this topic

[August1]

Hi everyone,

I've seen a lot of information on the interaction between TKI drugs and PPI medications. I've been taking PPIs for many years due to GERD. Also, I was diagnosed with Barrett's Esophagus last year. This puts me at higher risk for developing esophageal cancer.

I was first on Protonix and now Dexilant. Since going on the Dexilant the GERD has been under control and the Barrett's has improved but I'm also having a slower than optimal response to my CML treatment.

I am currently on 100 mg Sprycel. At this point, I've reached CCyR, but my last PCR was still at 0.3% after about 17 months of treatment. I feel that the PPIs are likely contributing to this.

So what do I do? I have been trying to balance the amount of PPI in my system to increase TKI absorption but I feel like I'm stuck between the two extremes. Neither of which presents a good outcome. Is is worth it to lobby for another TKI change to Tasigna or should I just want to see if my trend gets me to MMR and stick with that?

Thanks,

Bill

[Happycat]

Bill,

The PPIs cut down on the production of stomach acid.  The stomach acid helps to solubilize the TKIs.  Gleevec in particular has a lot of basic nitrogens and needs acid to make it soluble and bioavailable.  (Probably why they chose the mesylate salt form, too.)  Talk to your doctor to see if there is a TKI that is more readily absorbed when taking PPIs.  I can't say that the lower acid production is the main driver of the loss of effectiveness of TKIs, but simply as a chemist, it makes a whole lot of sense to me.  I work with a lot of drugs (we sell them to biologist for research) and we are always making salts out of them to improve solubility.

Also, ask your gastroenterologist if you can improve the GERD by taking a non-PPI drug.  Ranitidine (Zantac, I think) works by a different mechanism, so won't lower production of stomach acid.  (It's work on histamine receptors in the stomach, I believe, H2 or H5?  Can't quite remember.)  That's the one my onc has me take.  It occurs to me if you have been taking PPIs for years and still have Barrett's esophagus, then the PPI is not the drug for you.  It clearly isn't working to control the acid reflux.  Thus, changing to a different drug class with a different mechanism would seem in order anyway.

I urge you to get the GERD and Barrett's under control.  My dad died of esophageal cancer, and it was an ugly, painful way to go.  Don't just settle with taking the PPI.  I don't think it is working for you.  And if it isn't working, AND it's affecting the absorption of your TKI, then you have even  more reason to change drugs. 

Best of luck,

Traci

[August1]

Hi Traci,

Thank you very much for the feedback and I am so sorry to hear about your dad. That must have been incredibly difficult. I am definitely concerned about my situation and want to be sure I am doing the right things. I know this is our LLS site but I appreciate your feedback. As I mentioned, I had GERD prior to CML and I was taking a PPI but not really consistently. I remember having many episodes of acid reflux, especially when sleeping. When I started Gleevac I even went off of the PPI to help with Gleevac absorption. I didn't know anything about EAC and actually saw the Gastroenterologist due to GI side effects from Gleevac. Thank God I did. I had an upper endoscopy and the initial diagnosis was hiatal hernia (grandmother also had this), esophagitis and BE with no dysplasia, I also had a couple of small ulcers.

Following that diagnosis I was put on Dexilant 60 mg and we did a repeat endoscopy 60 days later. Overall there was a lot of improvement. The ulcers were gone, the inflammation had improved and the BE looked better. So it seemed like a good response but we are also doing repeat endoscopy every year. My next one will be in a few months. I've also elevated the head of my bed, sleep on a wedge pillow, and try to avoid eating or taking medication closer than two hours before going to bed. I have a follow up office visit in two weeks. So hopefully I can control the GERD but I fear it is coming at the expense of TKI absorption.The Sprycel site specifically mentions that PPI drugs can decrease uptake.  

If there is anything else you might recommend or anything I might bring up with the doctor I'd love to hear it.

Thanks,

Bill

[RayT]

Hi, Bill! Thanks for your post.  It made me add another question to my list for my hem/onc when I see him next week.

I was Dx'd with CML in January, taking Gleevec < 3 months now, just found out about the LLS website andthis discussion board this weekend.  I also have a hiatal hernia and have been taking Protonix for years. Additionally, I had a heart attack in 1985 and CHF, thanks to side effects of chemo for Hodgkin's disease then.

I hadn't heard anything about PPI and TKI interaction until this weekend, and my hem/onc didn't say anything.  I was aware of quite a few interactions among my cardiac meds and Gleevec, but nothing involving Protonix.  Fortunately, a quick internet search found the following article from the journal, Blood, (Am Soc of Hematology) that I found quite useful:

Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib,and nilotinib

http://bloodjournal..../8/e75.full.pdf

Other articles that I read (British Journal of Clinical Pharmacology, Euroean Hematology Assoc) indicate that Gleevec does not have the same issues with PPIs that exist with Tasigna and Sprycel.

I hope this helps...

[August1]

Thanks, Ray,

Wow, you've been through a lot and welcome to this site. I think you'll find a lot of good people and good advice here. I was on Protonix as well. In fact, I remember taking my Gleevac and Protonix at the same time when I was originally in the hospital following diagnosis. So the hospital at least had no objections to the interaction between those two. I did "OK" on Gleevac, no intolerance or resistance, I just wasn't having an optimal response and had some GI issues. That was why I switched to Sprycel. 

Given that I need to control stomach acid, it seems like Tasigna might represent the "best" choice given TKI effectiveness and the various drug interactions. I am just not sure if it's worth it to make the change. Currently my side effects seem to come and go, but at least they're manageable. You never know what to expect when making a drug change. I have an appt. in about a month and will discuss this in depth with my oncologist then. Appreciate the feedback.

Bill

[RayT]

My pleasure to help.  I'm a career paramedic and it stinks to be on the patient side of the stethoscope!    If only the fatigue, fluid retention and chills would subside...

[Happycat]

Bill,

Sorry, I don't have much experience with the BE management. My dad had heartburn problems and stomach problems as my mom puts it, but when he was dx'd and died back in 1984, I don't think the connection between BE and esophageal cancer was well recognized. And to be honest, my dad wouldn't have gone to the doctor for heartburn anyway.

The paper that Ray posted is a good one. It's the same one I came across when I was looking for cross reactions between imitanib and other drugs I take. I recommend you take it to your oncologist and gastroenterologist both. They need to work together on this to get you the care you need. I'm sure the onc has run into this problem before, and may have some good tips for you.

It sounds like you are taking serious steps to get the BE under control, which is good. Hopefully, once things have healed, you can switch to something else with less impact on TKI absorption. My only other advice for you is to lose weight if you are carrying extra around. I notice myself I have more reflux issues when my weight is higher. If I lose a 10 lbs or so, it improves.

Good luck,

Traci

[August1]

Thank you, Traci,

Appreciate your feedback.