Episode 126: Questions from near and far and answers from way out - Part II

Submitted by JPM on Mon, 2011-05-16 10:28

In episode 126, James and Mike discuss how to do a drugectomy and why one needs to consider evidence, efficacy, side effects, cost, patient preference and that as clinicians we need to do many "n of 1" trials. We then discuss the concerns around dabigatran and what to do about bleeding on this agent and why the FDA made the 150 mg dose the chosen one.

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Comments

dabigatran reversal

Submitted by pcat on Fri, 2011-05-27 20:50.

One of your questions addressed what to do pharmacologically for patients who are on dabigatran, and having major bleeding.

I've hunted around a bit and it appears, not surprisingly, there are few if any good clinical studies to help answer this. Here are a few references:

1) Regions Hospital in Minnesota, a trauma centre, has a protocol suggesting how to manage bleeding trauma patients (particularly head trauma) on dabigatran: http://www.regionstrauma.org/blogs/dabigatran.pdf
and http://regionstraumapro.com/post/5544225915

2) Cedars-Sinai in Los Angeles also addresses bleeds on dabigatran...in their pharmacy newsletter no less:
http://enewsletter.csmc.edu/Pulse/2010/December-17/Reversal-of-Dabigatra...

3) The hemostasis gurus as McMaster also have their ideas on dab reversal: http://www.fhs.mcmaster.ca/medicine/hematology/anticoag_dabigatran.htm

Bottom line: After discontinuing the drug...some combo of oral charcoal, dialysis, recombinant Factor VIIa or prothrombin complex concentrates intravenously (presumably Octaplex or FEIBA).

Paul

Hi Paul - thank for doing

Submitted by JPM on Tue, 2011-05-31 18:39.

Hi Paul - thanks for doing some leg-work on this - I'm not really sure how important this issue is when it comes to deciding between warfarin and dabigatran up front but it obviously is an issue in the 1% or so of people that get a bleed on this drug. Thanks again.

Have to avoid making assumptions about renal dosing

Submitted by Anonymous on Tue, 2011-08-23 12:01.

I listen to all the podcasts that you guys put together, and they are great. Handy to have on the iPod:)

I have one criticism about a comment made with respect to renal dosing of dabigitran. James made a comment that he would probably start a renal patient on maybe 75mg twice daily because dabigitran would be cleared less readily than in patients with healthy kidneys. Studies of thousands of patients were done to decide if 110mg vs 150mg dabigitran was an appropriate dose and so far it looks like 150mg is the winner. Since dabigitran is not monitored with something like INR, we have to assume that 150mg twice daily is doing its job based on the results of that evidence. I think it was a dangerous assumption that starting a renal patient on 75mg BID would provide effective anticoagulation, and maybe accurate monitoring of warfarin would be a safer choice (safer in the sense of controlling bleed risk and preventing stroke).

Maybe I was missing some evidence, or perhaps just don't have as great an understanding of renal drug clearance especially in renal patients, but I just wanted to bring the issue to light.

A lot of people listen to your podcasts and I think many practitioners take the suggestions you make very seriously. We listen to what you say. My comment is made in the interest of best care for our patients.

Thanks

Hi Anonymous - sorry I don't

Submitted by JPM on Fri, 2011-08-26 12:10.

Hi Anonymous - sorry I don't know your name

When it comes to dosing drugs in patients with renal dysfunction we are all basically woking in an evidence-free zone. I have thought a lot about this issue and have published a few things - see below and also created an iPhone app on this issue called KidneyCalc - on this issue.

McCormack JP, Cooper, J. Carleton B. Simple approach to dosage adjustment in patients with renal disease. Amer J Health Syst Pharm 1997;54:2505-9

McCormack JP, Carleton B. Dosage Adjustment in Renal Failure. In: Gray et al., eds. Therapeutic Choices – 5th edition: Canadian Pharmaceutical Association 2007

When there is no evidence I fall back on pharmacologial and pharmacokinetic pricnciples. My general philosophy is if a drug is renally eliminated and a patient's renal function drops below say 50-60 ml/min I think about reducing the dose empirically to decrease the potential of side effects.

I disgaree that one just sticks with the usual dose no matter what happens to their renal function.

The bottom line is none of us really know what to do so keeping the dose the same or reducing are both equally right and equally wrong recommendations.

At least that's the way I see it.

Thanks for your comment.

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