Bisphosphonates and Omeprazole

I know that a lot of people on Xeloda are prescribed Omerprazole (or similar) for acid reflux. These drugs are called Proton Pump Inhibitors or PPIs. I came across this article which states:-
“… PPIs can cut the effectiveness of bisphosphonates to almost zero, according to a study in the Archives of Internal Medicine last year.”

Bearing in mind that a lot of us are also on bisphosphonates, this is very worrying.

However, I also discovered some research showing that pre-treatment by PPIs can enhance chemo drugs on resistant bc cells:-

I also found this article suggesting that PPIs may replace chemo in the future but, needless to say, the drug companies are not very interested in researching this:-

(I think it comes from an Italian site and the translation is a bit weird but it is worth persevering to the end.)

All of this research makes the decision about whether to continue with bisphosphonates and PPIs rather difficult. Any thoughts, anyone?


I’m un-clear how they think PPI’s could change the acidity of cancer cells. As Scientists they will know that it is impossible to change the blood ph (without killing somebody), because normal cells cannot exist in an alkaline environment and the body maintains a system of checks and balances (called homeostasis). They appear to be saying that they think cancer cells seem to generate an acidic micro environment, but again I do not understand how PPI’s could change that.
Personally I doubt the theory. I’ve been on proton pump inhibitors since 2007, and by 2009 I had developed BC which was then diagnosed as secondary BC a few weeks later - so in my case it hasn’t prevented it or cured it. Also the info is very old, and based on animal models, and cells in petri-dishes). I am rather more concerned that Proton Pump inhibitors could inhibit the absorbtion of Cap, because PPI’s act on the Liver, and also because Cap is absorbed in the stomach.

Yes, I agree it is old information. I just found it interesting.

To be fair, the DM article did say that PPIs can cause serious illnesses such as cancer. My mother was on Losec and later developed breast cancer. I don’t know if there was a connection.

Did I miss where it said that PPIs may inhibit the absorption of Xeloda or did you get that from somewhere else? Wouldn’t the oncs be aware of this if that is the case?

Is anyone on PPIs and have found that Xeloda is working for them?

What do you think about the PPIs potentially inhibiting bisphosphonates?


Anne I suppose the reason that I’m wary of PPI’s is because when I was first prescribed them in 2007 (for another health issue), my GP said that I should take them a good hour before anything else because they could interfere with the absorption of other drugs. Also my Sister in law is a pharmacist, and she said that information was correct. Having said that I would have thought my Oncologist would not prescribe the two together if one counteracted the other - but you never know, so I take them an hour before the Cap just to be on the safe side.
By the way, do you happen to know if the research concerning PPI’s and bisphosphonates, applies to Zometa as well as Bondronat? I can understanding how PPI’s would inhibit oral bisphosphonates but can’t understand how they would inhibit infused.

It appears that it is an oral bisphosphonate (alendronate) that was studied. I tracked down this article:-

I haven’t had time to read it all, though.

I do try to make sure that I don’t take any of my other meds at the same time as Cap. However, I take my thyroxine tablet about 40 mins before the breakfast one. I tried taking it before bed but didn’t sleep well. I take the calcium/D3 at lunchtime as that cannot be taken with thyroxine. It all gets so complicated, doesn’t it?


Thank you Anne, that makes sense.
Do you take Bondronat or do your have bisphosphonates by infusion? I have Zometa by infusion, because the Bondronat didn’t seem to be working very well (makes me wonder if that could be linked to having PPI’s). I also have thyroxine (for an underactive thyroid), and Calcichew (as I also have a touch of osteoporosis), and I sometimes think my whole day revolves around timetabling drugs so that they don’t clash with each other. Sometimes I wonder if it would be better just to stop taking everything, and see if my body can sort itself out (but maybe that would be a bit like playing Russian roulette).

Lemongrove…my instructions written on the outside of my box of capecitabine says “do not take indidestion remedies 2 hours before or after taking this medicine” Not sure about any interactions with IV zometa tho. Pamx

Just to say went up to Charing Cross Hospital today, and the pharmacy confirmed that PPI’s such as Omeprazole must be taken at least two hours before or two hours after Cap. Have just looked on the Roche site, and it says the same thing. Am a bit worried about this, because I’ve been taking Omeprazole just an hour before the Cap.

Lemongrove - I am on IV Pamidronate. Yes, it is difficult to timetable all the meds. I read that Thyroxine should not be taken within four hours of calcium, so I have thyroxine when I get up and Adcal-D3 at lunchtime.

I have just looked through the Xeloda leaflet and I cannot see anything about interaction with these drugs. Did I miss it?

Pam - My capecitabine label does not mention indigestion remedies. I do wish there was some consistency among the medical profession. We seem to have to pick up information by hearsay.

Duplicate of post I put on Xeloda tips thread, cos one day these 2 threads will drift apart and I think it’s important info for future ‘victims’ of our current regime!!

Oh joy - it seems even the pharmacists can’t agree! I don’t particularly trust the oncs, GPs et al on the drugs front, but I have always put faith in the pharmacists. On reading Ann’s posts on Omeprazole and bone pills, and given I take calcium and Cap too, I thought I’d ask this morning when I collected my drugs. Scary aside - I walk into pharmacy - assistant smiles says hello and goes off to get my prescription without asking who I am - in there too often me thinks!!
The pharmacist checked twice, once on some kind of internet site then in her book, and said no reactions between Cap and Omprazole. She did recommend taking Omeprazole before food, and Cap definitely after, but that was it. I told her my routine - bone pill (ibandronic acid on wakening, 30 mins later all my other pills (anti depressants, beta blocker, Blood pressure, thyroxene, statin, aspirin, omeprozaloe, B6) then eat, then Cap. Exception being I take my calcium before bed on its own. She said this was exactly right!
I’m going to carry on as I am after that - I’ve had misleading advice from onc on anti depressant and tamoxifen when I was on that, which I got checked out with psychiatric pharmacist and onc was wrong, and I remember a GP telling me once the best person to ask was pharmacist as they know all the interactions.

This is news to me, I take my Omeprazole with Capecitabine and breakfast. Maybe that’s why I have progression in bones despite 15 cycles. Never been told any different, can’t see anything on the insert either. Am going to ask a pharmacy friend of mine then check with hospital pharmacist at next appt. thanks for highlighting it.

Hi Happyfeet…here goes! Only a personal view and you would be wise to check out with your hospital pharmacist…but having read the product specification data sheet…not an easy read even if you have some clue about these things! they talk about the importance of taking capecitabine with or within 1/2 hour of food. The rationale for this seems to be that this slows absorption…presumably important to reduce risks of side effects. they then go on to talk about antacids which contain magnesium or aluminium ie simple antacids and not proton pump inhibitors(PPIs). they comment that they also slow absorption of some parts of the active ingredients…but to a lesser extent than food!..they don’t however list this in their list of potential interactions and so clearly there are many more important interactions. My own hospital pharmacy do put a warning on the box of capecitabine warning against taking “indigestion remedies” 2 hours before or after capecitabine. this is a bit vague but probably relates to simple antacids…which doesn’t explain why Lemongrass was advised as she was. In summary. I think the interaction is probably a fairly minor one so panic not! Also i think it relates to magnesium and aluminium containing simple antacids. Bottom line. check out with your own hospital pharmacist when you get a chance! Pamx

Herbgarden, thanks for that. It’s all very confusing isn’t it? The European Medicines Agency say that antacids and magnesium indigestion remedies are contra-indicated if you’re taking Xeloda - so that begs the question, why are pharmacists saying it’s OK to take them, as long as it’s two hours before or after? Also I thought that PPI’s were a form of antacid (my understanding is that they stop acid production). If that isn’t the case, why are Charing X hospital pharmacy advising me to take them two hours before Cap? I have tried to contact Roche for clarification, but they only speak to health professionals. Maybe on of the BCC nurses could clarify this?

I’ll pass it on to the nursing team and see what they can say.

Posted on behalf of the Breast Cancer Care nursing team

Hello Lemongrove,

As you mention the Electronic Medicines Compendium states that antacids have been investigated when taken with capecitabine. It states that antacids may slightly increase plasma concentrations of capecitabine. You can read this in section 4.5 from the link below, although this information hasn’t been written from a patient information perspective:

However proton pump inhibitors (PPI’s) such as omeprazole aren’t strictly antacids. They work by reducing the amount of acid your stomach makes, as supposed to antacids which do not stop your stomach producing acid; rather they try to neutralize or protect against what is already there. See below for further information:

I have contacted Roche to ask if they know of any interaction with capecitabine (Xeloda) and proton pump inhibitors and they said they were not aware of any and that it was therefore an individual prescribing decision. I’m not sure why your pharmacist was suggesting taking the drugs two hours apart: perhaps just a precaution. I’m sorry I was unable to find the information on the Roche website that you mention.

Kind regards

Nursing team

Thank you for clarifying that BCC. Was worried that the PPI’s might have interfered with Cap. But will not be taking ant-acids or magnesium based indegestion remedies.

Many thanks for that info

Many thanks …good to have the definitive info. Pamx

Thanks to Leah and the Nursing Team.

Nina - Why do you have to take calcium before bed on its own? I thought that it should be taken with food to help absorption. I have mine at lunchtime.

Happyfeet - Is Xeloda helping with mets other than bone? I was just wondering why have you had 15 cycles, if not.

Well thank goodness that has been sorted out. I was taking both pills together for years and started to separate them this week…so back to the old regime which is easier as taking tablets twice a day is so much easier than 3 times as I am inclined to forget.
Thank you Leah for taking our questions further and getting this quesry sorted. But thanks everyone else who posted as it was good to compare notes. Great work. Whew! Val