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My pcr scare

Since I was diagnosed with CML, on Friday the 13th of December 2013, I have been gathering information about the disease and how to live with it. I am a biologist and love numbers and charts. This forum is extremely useful and welcoming. But before today, I was just a reader. I have a story to tell hoping that it could help others. Here it is.

I was put on Dasatinib, 100 mg, and reacted very well and quickly. It took me a year to get to MR4.5 and another year to reach below MR5. On January 2016, my pcr was 0.00046%IS. I was waiting for "undetectable" and agreed to do the next test in 6 months in July 2016. I was pretty happy and really began to relax and enjoy life. But at the end of January and end of March, I got 2 UTIs (urinary tract infections) and went to the ER for urine test and antibiotics. My doctor suggested to drink cranberry juice that is recommended to prevent UTIs. I decided to take cranberry extract, one softgel every day.

In July, my pcr came at 0.008%IS. I was first disappointed and second worried. I am sure that you all know the feeling. We love our numbers when they are going down and hate them when they dare to go up. My hematologist was not worried and told me that I was already pretty low and probably in the "noise".

My next pcr in October 2016 was 0.024%IS!!!! Three times higher than July and 50 higher than January. I was getting more and more worried and thought immediately about a new mutation that would be resistant to Dasatinib. Now I had 2 consecutive positive pcrs. I negotiated with my hemato to have the next test in December. I had 2 months to wait with my brain going into dark places. I sent my chart to another hematologist and specialist of CML. His email was very helpful. He said and I quote:

"Any changes in diet, supplements, other medications? In particular, need to avoid things that would activate CYPs. Culprit #1 is grapefruit. Also, need to avoid any antacids or proton pump inhibitors like prilosec. These block absorption of dasatinib."

And that's exactly when I realized that cranberry juice extract might be the culprit for me. I stopped the cranberry juice extract immediately and begun a serious search on Internet to find some information. I gathered a lot of circumstantial evidence that cranberry extract reacts with the famous CYPs (cytochromes P450) that my hematologist was talking about and interacts with a series of drugs. We can discuss this in detail if somebody is interested. I became cautiously optimistic for my next result.

My pcr result arrived finally at 0.0051%IS, five times lower. What a relief: I seem to be back on track with Dasatinib working well again.

So, my message to take home:

Stay away from cranberry extract when you take TKIs, the same way you avoid grapefruit. My experience may provide evidence that a cranberry softgel per day was enough to decrease the level of Dasatinib below the therapeutic range and put my health at risk. I don't necessary think that cranberry juice is as dangerous. In general, we need to be very careful with dietary supplements that are found more and more to interact with medications.

FYI, 60% of the new medications are using the same CYP (CYP3A4) for absorption and metabolism, therefore compete with each other, provoking potential serious drug-drug interactions.

Happy Holidays to you all.

Karinne

Hi Karinne,

Thanks for a really informative post. Luckily for me I hate cranberry juice! But all the same, it goes to show how important it is to take extra care when taking any new supplements, medication or change in diet.

Becasue dietary supplements are not regulated in the same way as medication, less is known about interactions. After reading your post I found an interesting article from EXCLI Journal which describes an attempt to understand how cranberry supplements interact with some medicines with regard to CYP3A4. Interestingly, out of the 9 cranberry supplements they tested all but one had little of no effect on CYP3A4. But one, branded "Nature's Herbs 600mg", had a very strong CYP3A4 inhibition effect. The reason was not known. 

So I think that really just hammers home the point that we all need to be extremely vigilant about drug interactions and supplement interactions. At the very very least, we all need to know what we are putting into our bodies so if there is a change in our CML we have the ability to correlate it with a change in what we are ingesting. Well done to you for catching the problem you were having.

From what I understand, and someone may come along and correct me, is that cranberry juice (rather than supplements) are generally considered to be OK to take with most medication including TKIs. Quite a lot of study has gone into P450 interactions with warfarin and I don't think a conclusive link has been found to cranberry adversely effecting it in any meaningful way. So I don't think cranberry juice itself is on the "don't drink" list alongside grapefruit juice for example.

David.

 

Dear David,

Thank you for your great response. And also for the reference to this interesting article that I did not have. As for the cranberry juice, I would stay clear of it, too. A group studied different cranberry juices and again like in the case of the cranberry extract, one shows a very strong effect and four others not so much (Drug Metab Dispos.). How would we know if the one we have is safe?