25 replies to this topic

[garfonzo]

Hello all, I thought it would be helpful to document this going forward. Briefly I have to take Fluconazole for probably a year to clear up a fungal lung infection. It is a CYP450 3A4 inhibitor. Like grapefruit it can increase the amount of the tki in your system. Although no testing has been done directly with these two drugs. Other tests with similar fungal drug (the 'azoles') have shown them to increase the Sprycel amount 4-5 times. Officially it is a moderate interaction expected with Spry and Flu, not a major one but advised to be avoided.
So we are starting with reducing my Sprycel from 100 to 40mg and adjust accordingly. Just started the Fluconazole. Continued frequent testing and EKGs to monitor.

I may post the official interaction language later but it's easy to look up.

I hope this self case study will be of benefit to others who will have to take another long term treatment of a drug that doesn't mix well with their Tki; both with the results and progress but also with the monitoring and adjustments. Will be watching for Sprycel toxicity of course. I'll post the progress and adjustments as they occur.

[garfonzo]

Fluconazole - Dasatinib
Moderate
MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations and pharmacologic effects of dasatinib, which is primarily metabolized by the isoenzyme. In a drug interaction study of 18 patients with solid tumors, coadministration of dasatinib (20 mg once a day) with the potent inhibitor ketoconazole (200 mg twice a day) increased the dasatinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 4- and 5-fold, respectively, compared to administration without ketoconazole. Data are not available for dasatinib in combination with other CYP450 3A4 inhibitors. Theoretically, a reverse interaction may also occur, since many CYP450 3A4 inhibitors are also substrates of the isoenzyme and dasatinib is an inhibitor.

MANAGEMENT: Caution is advised if dasatinib is used in combination with moderate CYP450 3A4 inhibitors. Close monitoring for toxicity (e.g., myelosuppression, bleeding complications, fluid retention) is recommended, and the dasatinib dosage adjusted as necessary. Patients should also be monitored for altered efficacy and safety of the concomitant administered drug.Moderation Interaction
Fluconazole , dasatinib

[IGotCML]

Thanks for posting this, it will be interesting to follow.

 

Is this only a "self case study" as you mentioned or will your results be available to other onc's treating other CML patients?

[garfonzo]

@IGotCML hi. I only describe it as a self study because there isn't much literature out they to go by so we are kinda winging it. The Sprycel rep suggested reducing from 100 to 60. I wanted 20 so my onc and I agreed to split the difference and start at 40. Wouldn't be too much of a issue if I only had to take it for a short while but this is going to be a yearlong thing. The key is finding that dosage level that is equivalent to my original 100mg.

[rcase13]

Is there some test that can be done to see how much Sprycel is in your system?

[garfonzo]

Not very good absorption tests out there I think without continual all day blood draws. Maybe because the half life is so short. ? My blood counts are pretty normal along with the typical low reds. We will monitor liver and kidney functions and regular ekg to watch the QT

[Buzzm1]

The Sprycel rep suggested reducing from 100 to 60. I wanted 20 so my onc and I agreed to split the difference and start at 40. Wouldn't be too much of a issue if I only had to take it for a short while but this is going to be a yearlong thing. The key is finding that dosage level that is equivalent to my original 100mg.

garfonzo, good luck in finding the right dose of Sprycel to accompany the Fluconazole; knowing that grapefruit can increase the tki dosage 4 to 5 times (I had an OD reaction on 100mg of Gleevec), I agree with your wanting to take to take 20mg to begin with.  If side-effects do occur, pleural effusion will likely be your first warning sign as it seems to be the most predominant Sprycel side-effect.  There are various test "toys" to roughly measure lung capacity.  When will you do your first PCR?

[garfonzo]

I'll probably do my PCR at my next regular quarter test 2 months from now. I've had no sign of PE so far after a year on Sprycel. Lung scans are clear of that. I really do feel great. I'll watch for those visible and other side effects that indicate more in my system than usual.

[garfonzo]

Brief update now after tests a little over 5 weeks into this.

Sprycel was reduced from 100 to 40mg to start.
ECGs done weekly are normal. Monthly for now on.
PCR went from .1 to .06 that's good.
Liver numbers are good. No toxicity so far.
Kidney numbers are elevated. Creatine 1.35 and GFR 57.
Everything else is still normal. Reds and whites are stable.
Kidneys will have to be watched. The Fluconazole can be hard on them too. I'm taking the highest dose 400mg for a long long year.
I also started on BP medicine Ramipril 5mg.
Who knows what is causing the kidney numbers. Creatine has always been high normal but this is the first time GFR was under 60.
Only side effect noticed has been new lower back pain. The same kind I felt when first starting TKIs.
Otherwise I feel great. Next tests are 3 weeks from now and I will actually visit my docs then.

Really no easy way to monitor the amount of Sprycel being absorbed in my system beyond more or less being surmised from side effects and effects on blood panels. It's good to the PCR drop but maybe it's because I've quadrupled my absorption rate. Oh well, just keep monitoring. I'm less worried about that than I am the high dose Fluconazole doing something to me.

[kat73]

garfonzo, it's great to hear from you again on this subject.  Only 47 weeks to go!  I'm glad you're being monitored so closely.  It's scary when the creatinine goes up - happened to me on Gleevec.  Mine stabilized, fortunately, at around 1.1.  I hope yours does, too, but they will have you followed by a nephrologist, I'm sure, and he will stay on it.  My guess is it is the fluconazole and not the Sprycel that's hitting the kidneys and I hopehopehope you can stay on it.

[garfonzo]

Thanks everyone. I appreciate the words and advice.
Just finished my onc visit. My labs look very good. CBC panel looks great and my creatinine and GFR improved to near normal for my kidneys. Liver is fine. BP was 117/70 and had lost about 5lbs. Changes I made from a month ago was to eliminate my supplements of magnesium, vit c and D. And to drink tons of water. I have more lab work next month with my PCP where I will get a full vitamin level breakdown to establish a base level. I may begin supplements again if warranted.
If my PCR comes back Friday with another drop from .06 or steady, my onc has agreed to let me cut my dose from 40 to 20mg. I think I am absorbing a lot of the Sprycel.

[kat73]

This is just great news, garfonzo!  So happy for you.  I think things are going to work out fine.

[Buzzm1]

Looking forward  to your Friday PCR result garfonzo; glad your GFR improved; wish mine would.

[garfonzo]

Almost 5 months into the 12 month antifungal treatment.
PCR remains just below MMR at .09
Earlier kidney issues from the Fluconazole seem to have settled and numbers are back down to high normal. Started drinking lots and lots of water.
Ceatinine 1.26 and GFR >60
Liver continues looking very good too.
CBC w differential also all normal aside from the usual slightly low reds. Everything is A-OK so far.
Going to try to reduce Sprycel from 40 to 20mg after being at 100mg prior to the lung infection treatment.

[Buzzm1]

good to hear that everything is going well garfonzo.

[garfonzo]

7 month update here. 5 months to go on the year long Fluconazole 400mg high dose per day treatment for a rare lung infection.
Still taking Sprycel 40 mg - reduced from 100mg Pre lung treatment. PCR tests have all been at .1 or lower. Not much movement there. Hard to tell how much the equivalent Sprycel dose is while taking the Fluconazole although I do ache in all the spots that had subsided previously at 100mg. That makes me think I am having more than 100mg although my PCRs aren't coming down much further. Plus my hemoglobin at 12 is below my normal low normal.
Creatine continues to back down 1.23 and GFR is above 60 so Kidneys are looking good again.
Liver is excellent too.
So all in all so far so good. Except, that my hair began to thin dramatically on top at the 3 month mark due to the Fluconazole. They didn't tell me this so that was a surprise. Oh well, it will come back next summer :-)
Lung scans will be done around month 9 or 10. Hopefully this will clear up and I don't have to go beyond 12 months on this stuff.

[garfonzo]

Two months to go and latest labs this week show all is well with kidneys and liver and the rest of the Panel results.
PCR continues at or below MMR. .07 this time.

Onc has agreed to keep my tki dosage at 40mg Sprycel after stopping the Fluconazole two months from now. (I was at 100mg prior starting fluconazole 10 months ago)

Next PCR is in 3 mths so probably won't get a good indication if 40mg will continue to work or not until the subsequent 3 mth test.

Lung scans next month. Hopefully those will show only residual scarring and we can consider this yearlong episode over. Nice case study though.

[M.A.]

Fantastic news re kidney, liver and MMR Garfonzo and good luck for your lung scans next month! I really appreciate you taking the time to post your experience as a case study. It will be so helpful for any of us who end up in the same situation.

 

Just wondering... how was the fungal lung infection detected originally? (symptoms, diagnosis) and do you think it had anything to do with the Sprycel?

 

Thank you!

[garfonzo]

Hi M.A.
It is Pulmonary Cryptococcosis. Usually found in AIDS patients with compromised immune systems.
It occurs naturally in nature and usually caught from spelunking in bat caves or being around pigeon droppings.

My theory is caught it from my pet parrot during my early CML time while my immune system was compromised.
My infectious disease guy considers me currently compromised from the Sprycel treatment but I don't buy into that. As I have learned here, our immune systems are fine once the CML is under control.

How it was discovered was that I had a heart scan done to get a baseline calcium score. They saw some "nodules" and stuff on what they could see of the lung incidentally. So i had a full lung by scan done that showed several nodules and stuff indicating lung cancer. I do a biopsy which was negative for cancer and positive for infection. Further tests showed the infection was cryptococcas. So after 2 weeks of needless worry we started this treatment.

Lucky it was caught before it can turn into meningitis.

[M.A.]

Thanks Garfonzzo, that is quite an ordeal you've been through!

 

Here's hoping you get the 'all clear' on the lung front next month and that your BCR ABL remains in retreat on the 40mg Sprycel!

 

Thanks again for sharing the details with us all.