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Nilotinib- stomach pain - pantoprazole

Hi Dav,

I didn't want this to get lost in the other threads so have started a new thread which I hope will help you with your question about nilotinib and possible interaction with pantoprazole the drug you take for stomach ulcer.

I am glad you have been able to resume therapy but.... not sure that you should be experiencing such discomfort after eating. I have taken a look at the various sites that list side effect of TKIs as well as contraindicated drugs and found that if you are having such bad stomach pain you really should inform your doctor as soon as possible.
Effects of taking nilotinib with pantoprazole (to control you stomach ulcer) may well be the cause of your pain/nausea. You said in your post to David that you take this drug about 1 hr before taking nilotinib.

I think you really need to push your doctor on this.. and maybe stop taking pantoprazole until you have seen him/her. You might also do well to ask for a referral to a CML specialist centre- I am not sure where you are and which centre would be most appropriate for you, but I am sure that would be possible and given you have a stomach ulcer you should be managed by people who have experience with TKi therapy.

According to rxlist.com Pantoprazol (oral and IV) is on the list of
'Medications known to have serious interactions with nilotinib oral' see link below and click on P to find this on their list of contraindicated drugs:
http://www.rxlist.com/drug-interactions/serious-index/nilotinib-oral.htm
and here:
http://www.rxlist.com/drug-interactions/nilotinib-oral-and-pantoprazole-...

It also says the following:
It (Pantoprazole)is indicated as having a possible 'serious' interaction with nilotinib which means it has the following warning: Serious
Potential for serious interaction; regular monitoring by your doctor required or alternate medication may be needed.

and

nilotinib oral and pantoprazole oral

nilotinib oral will decrease the level or effect of pantoprazole oral by increasing gastric pH. Applies only to oral form of both agents. Nilotinib has a pH-dependent solubility and solubility is decreased at higher pH; separating doses may not eliminate this effect because of PPI extended duration of action

Clinical Drug Interactions Source: Medscape from WebMD
© 1994-2014 WebMD, LLC.

Sandy

I posted a reply in the other thread ... but in case it gets missed, here it is as well!

Hi ...

I'm not having too many problems, and the ones I do have (gas, bloating) are getting better every week. So far, the results of the operation have exceeded my expectations and I am really pleased I did it.

Pantoprazole is a proton pump inhibitor (PPI). This is similar to the medication I was one (omeprazole). With the exception of imatinib, as I understand it, PPIs are really not compatible with TKIs. The guidance from the drugs companies is to use shorter term acting antacids as a means to control acid problems, rather than long acting PPIs. But lots of patients find that this isn't enough to control their symptoms (like me!).

From drugs.com : "Chronic use of proton pump inhibitors or H2 antagonists may significantly decrease the oral bioavailability of nilotinib. The mechanism is decreased solubility of nilotinib due to increased gastric pH. Nilotinib's solubility is pH dependent and it is insoluble at a pH of 4.5 or higher."

Along with Sandy, I really think you need to challenge your doctor on this. It's not totally impossible to take PPIs with TKIs - they are not necessarily dangerous together, but the PPI can significantly reduce the effectiveness of the TKI ... and I know where my priorities lie. The options we considered for me was to (a) have the surgery and take 100mg dasatinib, or (b) keep the PPIs and take 140mg of dasatinib. I prefer not to take more of the TKI than required for various reasons, and I was pleased to come off the PPI too.

I decided to go the surgical route to fix my reflux problems. Before, my PCR results were not terrible, but were stubborn and I am not in MMR and my doctor and I felt that this could be related to the PPI. I am awaiting a PCR result which was from blood taken a month after I came off PPIs - maybe too early to see a difference, but maybe not? Long-term use of PPIs isn't great in any case, especially at my relatively young age where I would need to be on them for a long time. I was told by the surgeon that performed my fundoplication they can cause bone problems later in life.

The particular procedure I had is great for reflux, but I don't believe would do anything for an ulcer as what it does is stop the acid from entering the throat, but of course the acid would still be in the stomach agitating an ulcer. I think it would be worth asking your doctor for a referral to a gastroenterologist to discuss alternative treatments for your ulcer which are more compatible with your TKI.

David.

Many thanks David.

It is good to get some answers from people who have actually had experience with using PPI's and TKIs together. I am slowly picking up the medical lingo!

I have an appointment with my doctor tomorrow and already have a rather long list of questions. We shall see where we get with all of it. Today I have not yet taken any pantoprazole and I managed to eat lunch without any stomach ache coming on (quite relieving). However the food flushed right though me about an hour later. I have had this problem for about 3 weeks which I believe must be a side effect of Tasigna. I can live with that - it was the stomach aches (followed by feeling exhausted) which were harder to manage.

Seeing as though I had no stomach ache today as soon as I had eaten food, I am coming to a part conclusion that taking PPI's and TKI's quite close together can be the cause of this stomach ache. The PPI's lower the acidity of the stomach so the TKI's do not have the chance to dissolve as quickly as they should. Eating food a little later when the TKI has not been absorbed properly (or not at the correct rate) might therefore lead to stomach pains... that's the logic which I can follow.

One doctor said to me I can break the Tasigna capsules and mix them with water, then swallow that. The Tasigna itself is quite acidic, and if the capsules always lie in the same place in the stomach this might cause a small stomach ulcer. Again I am not sure about that but seems to be logical.

So I will see how I fair in the next few weeks. If my stomach problems can improve then I really would be a happy camper.

Thanks again for the support.

Dav

Hi Sandy,

Thanks for the reply.
Yes I am feeling quite sure that the Pantoprazole (in combo with Tasigna) is the cause of the stomach aches. The stomach ache really came on quite quickly, 5-10 minutes after eating. I forgot to say yesterday, but it was followed by feeling extremely drowsy. I could not do much more than lie down and wait for the stomach pain to subside. I will see how I do over the next few days, as I have decided not to take any Pantoprozole for the time being (to test the theory).

My stomach in general still finds it very difficult to hold on to any food (problem I have had for 3 weeks)... This is not to do with the Pantoprazole but I believe just a side effect of Tasigna. Interestingly I did not have this problem when I first used Tasigna, only when I came off it and went on it again. It all started when I picked up a stomach bug from my children, which never seemed to leave me.

Will speak with the doctor tomorrow. I am actually living outside the UK but am going to start looking at where the nearest CML clinics are.

Thank you again. Yes - finally finding my way around this forum. Good job you set it up!

Dav

Hi Dav,

I would just like to underscore what David has already said... the advice from Novartis (the manufacturer) is that you should not break the tablets but if there is difficulty swallowing them then it is possible to crush them and mix them with apple sauce. Apples are in any case great for over acidity and my mother (who has suffered from this kind of condition for a long time) finds that eating apples in any form (but without added sugar) is really helpful. She has also found that a herbal tea called Matula has given her a new lease of life. She had to take 1 cup 2 times a day for 30 days. Since finishing the course she no longer suffers from gastrointestinal problems which for her is a bit of a miracle. She has been treated with anti ulcer meds but did not find that they helped in the longer term.

Please do try to find a CML expert who has experience with TKIs and their side effects. If you do not want to say where you live on this forum then contact me privately on CMLsupportgroup@gmail.com and I will do my best to help you find an expert clinician in your region.

Sandy

Dav,

One thing to note is that PPIs stay active for quite a long time - they lower the stomach acid all the time, not just for a couple of hours after you take it (like an antacid). So, it may take a while for it to "wash out" of your system completely. I'm not sure of the exact, or even an estimate of how long that would take on that drug.

With regard to breaking the nilotinib capsules and mixing them in water, do be careful. In a glass of water much of the drug could be left on as residue on the glass and you could be under-dosing (maybe just a small bit!) by accident. Here's the advice from Novartis:

"Tasigna should be taken twice daily at approximately 12-hour intervals and must be taken on an empty stomach. No food should be consumed for at least 2 hours before the dose is taken and for at least 1 hour after the dose is taken. Advise patients to swallow the capsules whole with water.

For patients who are unable to swallow capsules, the contents of each capsule may be dispersed in 1 teaspoon of applesauce (puréed apple). The mixture should be taken immediately (within 15 minutes) and should not be stored for future use."

If you are having terrible stomach aches, get seen by a gastroenterologist. They can work wonders.

What is your schedule with nilotinib? How long are you leaving it after taking the TKI before eating?

David.

Dear Sandy,

Thank you very much for the links!

My mother was on Imatinib (Gleevev) for 5 years, and 2 days ago she changed to Linotinib (Tasigna) she takes PPI (Pentropazole),she does not have stomach ache but we are afraid of the decrease of effectiveness of Tasigna due to the insolubility issue with pH higher than 4.5, do you think if she takes the PPi at nigh after two hours of her night dose is OK? Regards, 

Diana 

Hi Diana,

I take Sprycel / dasatinib, which has a similar requirement for stomach acid and thus isn't good to mix with PPIs. PPIs are quite long-lasting so it's not really good to take them at any time with TKIs. 

Having spoken to the drug manufacturer, they advise that you do not take PPIs at all with TKI drugs for CML. The advice I was given was to use a short-acting antacid, such as Gaviscon, around 2-3 hours after your TKI. You want your stomach acid to be at its highest point when you take the TKI.

In the end, I decided to get a surgical solution to my problems which worked out well for me - though I know that's not ideal for everyone.

Do you think your mother could get by using shorter acting antacids?

David.

PPIs a blanket approach-then interactions!

Hi All,

I suspect that the provision of PPIs as a remedy for stomach issues and irritation is a blanket approach from GPs . However a  significant proportion of certain stomach ulcers are a result of the bacteria H.Pylori.This is diagnosed after an endoscopy (camera and biopsy) or apparently by a breath test.-quite costly.So as a first point I would be unhappy to take PPIs on a long term basis in the absence of further investigations especially if on TKIs.

Upon the diagnosis of a H.Pylori bacterial stomach infection the usual therapy offered is the administration of  really high dose antibiotics say for one month of Amoxycillin plus  another supplementary  antibiotic  and also higher dose PPIs- some interaction  of Amoxycillin with TKIs as a risk I suggest?

Referring to the Haoula et al article (indicated  to in a previous thread), where it suggests that PPIs with imatinib lead to Imatinib exposure or greater uptake;to a severe decrease in Dasatinib absorption as a result of PPis (actual studies confirm) then I would avoid them. In the article there is no mention of any interaction with Nillotinib.From  previous comments/ sources on this thread  it appears that there are interactions of Nilotinib and TKIs. It may be because of the specific dosing regimes of Nilotinib i.e.twice per day and fasting,that interactions may be more indicated or as yet not totally identified.

So on the use of antacids such as Gaviscom  used on a short period basis that might alleviate symptoms it may be relevant to consider the make up of this medication and to consider if its ingredients  contraindicate any TKI- e.g.aluminium hydroxide being a long standing ingredient of antacids is not recommended as a therapy for stomach issues alongside TKIs because they interfere with the uptake..

I asked my Boots pharmacist to investigate the make up of Gaviscom versus Boots own Heartburn Relief in relation to interaction with a TKI and the generic came out best especially if taken at times away from the TKI say 6 hours apart.

I go back to my point from previous threads that GPs and even clinicians fail to, address drug interactions with TKIs

The alternatives to PPIs and antacids are more natural remedies such as Mastic Gum, probiotics-live yoghurt , Manuka honey ,cranberry juice, edible herbs and olive oil?Do any of these interact with TKIs -previous thread and Manuka Honey/TKIS perhaps?

Worth a try?

Best wishes

John

 

 

I would add Matula Tea to that list John. My mother suffered badly for years from H.Pylori infection and she found great relief from her symptoms by using this tea. It is expensive but you only need to take it for 30 days or so... re-take if reinfected by someone else. 

Also coconut oil; apple cider vinegar and good pro-biotics are recommended by many.

Sandy

I've posted this before but just for completeness, my original CML consultant suggested omeprazole for the moderate to severe heartburn I was getting with imatinib.  All the other consultants I've seen since ( four) have said it is ok to take these two.  It's my understanding that the problem with other TKIs is that they require an acid environment hence any medication that may reduce that could reduce the effect.  This is not the case with imatinib.  I took imatinib and low dose omeprazole (10mg per day), daily, for about 6 years with no problems, no heartburn and excellent response to imatinib (undetectable within 6 months).  

Now that I have stopped imatinib in the Destiny trial, I am no longer taking omeprazole although I am happy to take it occasionally - my family has a history of acid reflux so I do get it albeit a lot less often now.  I guess it's a matter of personal preference but I was and am happy to take omeprazole at least, and with imatinib.  Both worked well, for me anyway.

 

Richard