Acalabrutinib + Ruxolitinib interactions

[antonb]

Hello

I have CLL (taking Acalabrutinib ) I also have Myelofibrosis and my Dr might put me on Ruxolitinib.....

I am Looking for interactions between both drugs.

I have checked drugs.com and Epocrates

Looking for someone with more info or someone taking this combination

Thank you

[lankisterguy Volunteer]

Hi antob,

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We had a similar discussion 3 days ago about drug drug interactions, please see this posting and the helpful replies:

healthunlocked.com/cllsuppo...

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We have had 14 previous posts discussing ruxolitinib (Jakavi) healthunlocked.com/cllsuppo...

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Len

[cllady01 Former Volunteer]

Are you in Canada? The following was a proposed trial in 2016/17 of Ruxolitinib + Ibrutinib

that might help you to decipher side effects by reading the details for acceptance AND the related articles included. It doesn't look like the trial ever got off the ground??? or it may be that you are one of the intended participants for the trial? (Also, looking at the Drug Company insert info for each of the medications can give you an idea if you can feel good about these two medications for your rare concomitant diagnosis.

clinicaltrials.gov/ct2/show...

From all indications your situation is quite rare, so having a match here may not happen. I hope you can garner some info from the above (if you haven't already done so.)

[SofiaDeo]

They are both kinase inhibitors, and they are both metabolized by the same set of liver enzymes. So there is a *potential* for one or the other to hang around in the blood longer, since they are competing for the same set of liver enzymes. No way to predict if you have enough liver enzymes for both drugs to have plenty of liver enzyme receptor sites at the same time. Of you could stagger the doses, that would be my recommendation, but with both of them being twice a day dosing, this might be a tad difficult. Especially if you need food to take the late dose, and food in your stomach interferes with good sleep. You don't *need* to take food, but some of us do to manage nausea or other stomach upset from some meds. A large glass of water when taking the med is ideal, but taking a lot of water near bedtime isn't ideal either. Getting up to use the bathroom will also interfere with good sleep.

But there isn't an interaction in the sense that either drug inhibits(slows down) or induces (speeds up) the liver enzymes. You can read that acalabrutinib is an inhibitor of the liver enzymes, but it is considered a "weak" inhibitor and generally not thought to be clinically significant. But Murphy's Law says that someone, somewhere will get a stronger liver enzyme inhibition with acalabrutinib than expected. But I doubt there is any test data to verify the interactions between these two, it's not listed in the WebMD interaction checker and so Epocrates and Drugs.com won't show interactions either. So IMO it's just, monitor for side effects and report any symptoms promptly. I would also consider more frequent monitoring tests initially, including the lipid panels for the ruxolitinib. Just in case you don't metabolize things as expected. I had an instance of the drug the package insert stated should be cut due to drug interactions increasing its concentration, be the drug *not* elevated, the other drug got elevated and that other drug was reduced. So it's not set in stone, it's possible for things to occur not as planned/expected. Hence my recommendation to monitor more closely than "normal" if one wasn't taking 2 drugs.

If you are already stable on acalabrutinib, if it were me, I would try to separate taking the 2 drugs by at least 2 hours. But IDK if you will get GI upset at taking the ruxolitinib before bedtime on an empty stomach, after the acalabrutinib. Or perhaps your doc wants to shorten the acalabrutinib schedule to every 10 hours, and try to get the ruxolitinib on 12 hour dosing. Or both on 10 hour dosing, spaced apart 2-3 hours. It will need to be finessed a bit. But with both being potentially immune & marrow suppressing, I would *not* recommend taking both at the same time, together. At least not initially. If you don't get unwanted marrow suppression, it might be possible to take both at the same time. But not when adding the second med.

pubmed.ncbi.nlm.nih.gov/300...