On 10/17, my husband was diagnosed with a recurrence of GBM and was removed from his PD-1 trial. We are now anxiously awaiting another resection and, in the meantime, are investigating potential off-label treatments like Celebrex. Unfortunately, Celebrex apparently increases the chance of bleeding when taken with anti-coagulants, which my husband must take.
I am writing to ask if you or your loved one are taking both Celebrex and Warfarin (or a similar anti-coagulant) and what your experience has been with them. I think this can be addressed by low dosing and careful monitoring, but I would prefer to proceed based on concrete experience than on speculation.
Thank you for your sharing your information.
Margaret
I can't speak from clinical experience, but in theory selective COX-2 inhibitors like Celebrex should not be as problematic as non selective NSAIDs that also inhibit COX-1, in terms of blood thinning.
ReplyDeleteCOX-2 preferentially leads to synthesis of prostacyclin which have anti-platelet aggregation effects. COX-1 preferentially leads to synthesis of thromboxane which induces platelet aggregation. One would then expect COX-1 inhibition to cause more blood-thinning than COX-2 inhibition. This is the reason COX-2 inhibitors are associated with increased risk of cardiovascular events (by inhibiting prostacyclin synthesis without inhibiting thromboxane synthesis). However, Celebrex is not as selective a COX-2 inhibitor as other coxibs such as rofecoxib (which was removed from the market in 2004), and has minor activity against COX-1.
Ibuprofen and naproxen have slightly more activity against COX-1 than COX-2. Aspirin is more of a selective COX-1 inhibitor (hence the problems with blood thinning, and use in prevention of heart attack/stroke).
However, I realize that theory is not always sufficient to explain what happens in practice, so it would be good to have a doctor weigh in.
I'd agree with Stephen's words above.
ReplyDeleteWhen I was in practice, I prescribed both coumadin and celebrex, though not together, and not with GBM patients. My knowledge of these agents suggests that combined use might be reasonable in many cases, with caution.
So I did a Pubmed search, and there's one study that suggests any increased risk of bleed with combined use is very small:
"Bleeding complications in patients on celecoxib and warfarin."
https://www.ncbi.nlm.nih.gov/pubmed/16164494
Conclusion:
"There is a mild but non-significant increase in bleeding complications in patients taking celecoxib and warfarin compared with those taking warfarin alone."
Also worth reviewing:
"Does celecoxib potentiate the anticoagulant effect of warfarin? A randomized, double-blind, controlled trial."
https://www.ncbi.nlm.nih.gov/pubmed/16804099
Conclusion:
"Our results suggest that treatment with celecoxib does not potentiate the INR when taken with warfarin."
In all, it would appear that combined use creates very little increased risk of bleeding.
From the perspective of the patient, combined use makes sense in this situation--COX-2 inhibitors look helpful for GBM in pre-clinical data. From the perspective of a prescriber, creating any increased risk by using an unproven agent (the COX-2 inhibitor) for GBM is hard to ethically justify.
Even a cautious prescriber, though, might well be swayed by the presence of any other condition that might merit use of celecoxib, such as ordinary osteoarthritis. If he has any arthritis, showing the doctor the studies above might be persuasive.