Dabigatran Versus Warfarin

[Sparda29]

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Do you guys think that not having to monitor Dabigatran is an advantage of its use compared to Warfarin?

My preceptor had an interesting viewpoint on this in that the fact that warfarin needs to be monitored can be a good thing in terms of efficacy in safety compared to Dabigatran, where the monitoring parameter would be an incident of systemic embolism or stroke (unless you can monitor Dabigatran via a test or lab study)?

 

[PumpkinSmasher]

Do you guys think that not having to monitor Dabigatran is an advantage of its use compared to Warfarin?

My preceptor had an interesting viewpoint on this in that the fact that warfarin needs to be monitored can be a good thing in terms of efficacy in safety compared to Dabigatran, where the monitoring parameter would be an incident of systemic embolism or stroke (unless you can monitor Dabigatran via a test or lab study)?

Sure, you can list some advantages of having the patient come in for monitoring but overall not having to monitor is an advantage.

 

[ucrx]

Do you guys think that not having to monitor Dabigatran is an advantage of its use compared to Warfarin?

My preceptor had an interesting viewpoint on this in that the fact that warfarin needs to be monitored can be a good thing in terms of efficacy in safety compared to Dabigatran, where the monitoring parameter would be an incident of systemic embolism or stroke (unless you can monitor Dabigatran via a test or lab study)?

Do you monitor therapeutic enoxaparin in most patients? If a drug has a predictable dose response curve and few interactions that would alter it, what would be the need to monitor?

I would say the monitoring could be a good thing, if we were effective in keeping our patients INR in therapeutic ranges. Unfortunately noncompliance, diet changes, interactions, and professionals not knowing what they're doing with warfarin get in the way. INR control in clinical trials is probably better than in the real world, and dabigatran had a similar safety profile to warfarin in trials. To me, cost (insurance coverage) and renal dosing are the main limitations to dabigatran.

 

[PumpkinSmasher]

To me, cost (insurance coverage) and renal dosing are the main limitations to dabigatran.

I consider lack of a reversal agent and GI intolerance pretty darn important too.

 

[Sparda29]

Do you monitor therapeutic enoxaparin in most patients? If a drug has a predictable dose response curve and few interactions that would alter it, what would be the need to monitor?

True.

I consider lack of a reversal agent and GI intolerance pretty darn important too.

GI intolerance according to the trial is because they use tartaric acid as the core in the pellets inside the capsules because low pH is better for the drug.

 

[ucrx]

I consider lack of a reversal agent and GI intolerance pretty darn important too.

I forgot about those. There isn't a clear choice and it certainly requires weighing patient factors. Dabigatran isn't the wonder drug people were hoping it would be, but it is nice to have options.

 

[pandapharmer]

GI intolerance according to the trial is because they use tartaric acid as the core in the pellets inside the capsules because low pH is better for the drug.

Yeah that's the explanation but it's still an issue. I had just one patient who was on it and he stopped taking it (or went mail order and found another pharmacy or solution bc we haven't been filling his warfarin) because of the GI upset. We read the article for journal club in P&T this year...I don't remember the exact number but I thought they touched on the fact that a significant amount of patients experienced the upset and surmised that the majority who dropped out were because of that.

 

[PumpkinSmasher]

True.



GI intolerance according to the trial is because they use tartaric acid as the core in the pellets inside the capsules because low pH is better for the drug.

Yep. Unfortunately, I do not think Boehringer did any subgroup analysis to see if GI intolerance was reduced amongst those concomitantly using PPI/H2RA. How often are patients going to decide to skip the evening due to an already upset stomach or the fear of GI upset...

 

[spacecowgirl]

I consider lack of a reversal agent and GI intolerance pretty darn important too.

And the lack of trials in patients CrCl <30 ml/min despite approving an unstudied (for efficacy) dose in those patients. As far I as I know, only PK studies were done to get that dose. And the fact that 110 mg has fewer ADRs but isn't marketed. Strange.

GI intolerance according to the trial is because they use tartaric acid as the core in the pellets inside the capsules because low pH is better for the drug.

But did they change that for the marketed product?

I'm still excited about dabigatran, but I'm not totally convinced about it replacing warfarin just yet.

ETA - too slow in my posting - looks like GI issues are still a problem.

 

[PumpkinSmasher]

Yeah that's the explanation but it's still an issue. I had just one patient who was on it and he stopped taking it (or went mail order and found another pharmacy or solution bc we haven't been filling his warfarin) because of the GI upset. We read the article for journal club in P&T this year...I don't remember the exact number but I thought they touched on the fact that a significant amount of patients experienced the upset and surmised that the majority who dropped out were because of that.

For dyspepsia in the RELY trial the NNH was about 20 in the 150mg dabigatran arm.

 

[PumpkinSmasher]

Double post

 

[PumpkinSmasher]

I'm still excited about dabigatran, but I'm not totally convinced about it replacing warfarin just yet.

Definitely. It will be interesting to see if the FDA approves rivaroxaban...J&J submitted an NDA for it in early January.

 

[All4MyDaughter]

I've got a bounce back patient right now who was discharged on dabigatrin about 9 days ago and never filled it because it was $300. I can't confirm or deny those cost numbers, but that's what the patient said. It's definitely cost prohibitive at this point.

But... warfarin use in the community scares me b/c I feel like no one is monitoring the vast majority of patients on it. Or they aren't monitoring it properly. We do a pretty good job of monitoring it at the VA but community docs (in general) don't monitor as aggressively.

I just reviewed an article on Apixaban vs. Aspirin for A fib. Someone else at today's JC reviewed an article on Rivaroxabin. It must be anti-coagulation day!

 

[owlegrad]

I've got a bounce back patient right now who was discharged on dabigatrin about 9 days ago and never filled it because it was $300. I can't confirm or deny those cost numbers, but that's what the patient said. It's definitely cost prohibitive at this point.

But... warfarin use in the community scares me b/c I feel like no one is monitoring the vast majority of patients on it. Or they aren't monitoring it properly. We do a pretty good job of monitoring it at the VA but community docs (in general) don't monitor as aggressively.

I just reviewed an article on Apixaban vs. Aspirin for A fib. Someone else at today's JC reviewed an article on Rivaroxabin. It must be anti-coagulation day!

Curious what makes you say that? I only ask because I really have never really heard that concern before. Don't outpatients typically go to a coumadin clinic? Or am I showing my naivety? 😉

 

[Sparda29]

Curious what makes you say that? I only ask because I really have never really heard that concern before. Don't outpatients typically go to a coumadin clinic? Or am I showing my naivety? 😉

What's gonna make them come back for tests. Anyway, I read somewhere that there are INR tests that you can do at home and they are just as accurate as tests from a professional lab.

 

[owlegrad]

What's gonna make them come back for tests. Anyway, I read somewhere that there are INR tests that you can do at home and they are just as accurate as tests from a professional lab.

If they want more warfarin...

Edit: Not sure how I feel about testing at home. The home monitors are accurate, but I wouldn't feel comfortable with that at all, unless I was very comfortable with them and knew they could handle it. I would still want routine monitoring.

 

[spacecowgirl]

Curious what makes you say that? I only ask because I really have never really heard that concern before. Don't outpatients typically go to a coumadin clinic? Or am I showing my naivety? 😉

I'm curious too. I feel like the patients admitted to our hospital are pretty closely monitored.

Although I'm not all that sure that close monitoring helps much for TTR. IIRC, the data shows this as well. Even with the inpt dosing we do, I feel like it's chasing numbers more than anything else.

 

[owlegrad]

I'm curious too. I feel like the patients admitted to our hospital are pretty closely monitored.

Although I'm not all that sure that close monitoring helps much for TTR. IIRC, the data shows this as well. Even with the inpt dosing we do, I feel like it's chasing numbers more than anything else.

Yeah, daily monitoring/adjustment is pointless, but that is exactly how we do it on the inpatient side.

 

[PumpkinSmasher]

I've got a bounce back patient right now who was discharged on dabigatrin about 9 days ago and never filled it because it was $300. I can't confirm or deny those cost numbers, but that's what the patient said. It's definitely cost prohibitive at this point.

Price sounds about right. It will be interesting to see what most PBM have/will do with dabigatran. Tier 3 with a PA or documented warfarin failure (how will they define failure exactly..) or maybe unrestricted Tier 2 or Tier 3 with co-insurance/copayment.

Patients accustomed to picking up warfarin for $0-4 bucks are going to be in for a shocker when they see the copay. Important for the community pharmacists to remind them it is a trade off for no more INR monitoring and the costs associated with that.

Just wait, I am sure there is or will be a Pradaxa savings card distributed to cardiologists, just pushing patient economic issues down the road 6-12 months. This is a situation where the patient needs to be well informed about the 2 options, pros vs cons and leave it up to them which medication is the best choice for their life and financial situation.

 

[All4MyDaughter]

I'm curious too. I feel like the patients admitted to our hospital are pretty closely monitored.

Although I'm not all that sure that close monitoring helps much for TTR. IIRC, the data shows this as well. Even with the inpt dosing we do, I feel like it's chasing numbers more than anything else.

I'm at a community hospital now and I'm frightened by the number of people admitted with sub or supratherapeutic INR. Some of them we're just finding incidental to other problems.

While on my psych rotation we also covered a psychiatric prison. NO ONE there was within therapeutic range. Most were subtherapeutic. But we had one patient with an INR of 8 and it took us DAYS to get it d/c'ed. The docs just weren't aggressive about monitoring.

And I know this isn't hard evidence but when I worked retail we had patients who were on the same dose of warfarin for years, no adjustments, nothing. When I compare that to the frequency of adjustments I observe amongst our VA patients, I have to wonder. But maybe it's better than I think?

 

[owlegrad]

I'm at a community hospital now and I'm frightened by the number of people admitted with sub or supratherapeutic INR. Some of them we're just finding incidental to other problems.

While on my psych rotation we also covered a psychiatric prison. NO ONE there was within therapeutic range. Most were subtherapeutic. But we had one patient with an INR of 8 and it took us DAYS to get it d/c'ed*. The docs just weren't aggressive about monitoring.

And I know this isn't hard evidence but when I worked retail we had patients who were on the same dose of warfarin for years, no adjustments, nothing. When I compare that to the frequency of adjustments I observe amongst our VA patients, I have to wonder. But maybe it's better than I think?

Well I am hopelessly bias in this case because my hospital does do daily monitoring inpatient and all our patients go to a clinic to get their scripts/monitoring. I hadn't ever really thought of patients getting scripts without being properly monitored - that would be pretty negligent, imo.

It is an interesting topic though - I had always just kinda assumed that was the norm for coumadin patients. I did notice that several people get the same dose again and again at CVS, but when I shadowed at a coumadin clinic they always wrote the exact same script no matter what the patient's INR was (within reason of course) and just gave a dose calander to the patient. (something like M-W-F 2 mg, T-TH-SAT-SUN 3 mg - but as a nice calendar, not just written instructions - I REALLY liked the calendars, I thought they were a great way to give somewhat confusing information in an easy to read format). What I am trying to say is, the patient's actual doses did change most visits, but their scripts did not (for the most part) - so I wouldn't see the update just from filling the script at CVS.


*Wow!

 

[Ackj]

We had a guest lecturer from a local hospital and they mentioned that dagibatran is about $8/day, whereas daily INR is $7 + a few cents for the warfarin. On the outpatient side, you're certainly not getting daily INR, so the pricing gets skewed toward warfarin for now.

 

[owlegrad]

We had a guest lecturer from a local hospital and they mentioned that dagibatran is about $8/day, whereas daily INR is $7 + a few cents for the warfarin. On the outpatient side, you're certainly not getting daily INR, so the pricing gets skewed toward warfarin for now.

Yeah, we don't use it at all - I don't have the numbers in front of me, but it wasn't even as close as the one's you provided. Even with monitoring warfarin was the clear winner.

 

[MindOverMatter]

Have we seen any data about the cost-effectiveness of the two approaches in terms of the patient's out of pocket expense? I remember reading a study a few months ago showing that dabigatran was cost-effective when adding all the indirect costs associated with warfarin, but it really seems like the insurance copay is what's going to drive the market here.

I only have 1 or 2 patients on it right now. I'll have to check their copays tomorrow.

 

[ForcedEntry]

It needs weight-based studies.

 

[spacecowgirl]

Someone at work put together a nifty calculator to show at what point you break even, but it all depends on the frequency of monitoring and who (nurses or pharmacists) is doing it. And of course that really doesn't mean squat to the patient who only cares about OOP costs. I will check it out tomorrow.it's not formulary for us yet so I haven't seen it.

 

[tackett26]

Do you guys think that not having to monitor Dabigatran is an advantage of its use compared to Warfarin?

My preceptor had an interesting viewpoint on this in that the fact that warfarin needs to be monitored can be a good thing in terms of efficacy in safety compared to Dabigatran, where the monitoring parameter would be an incident of systemic embolism or stroke (unless you can monitor Dabigatran via a test or lab study)?

Well also consider with warfarin you have an "undo" button with Vitamin K, but you don't have that with dabigatran.

 

[meister]

We switched a few elderly folks with good insurance due to it being prohibitively expensive transporting them to the office regularly for INR checks and that was about it. It is really effin expensive.

The reps were fierce about it.

 

[PumpkinSmasher]

We switched a few elderly folks with good insurance due to it being prohibitively expensive transporting them to the office regularly for INR checks and that was about it. It is really effin expensive.

The reps were fierce about it.

The out of pocket cost to the patient is pretty high, even when it is covered. It will be interesting to see how J&J price Rivaroxaban when/if it gets approved in the coming months.

 

[owlegrad]

Well also consider with warfarin you have an "undo" button with Vitamin K, but you don't have that with dabigatran.

The idea of course is you won't need it. If uncontrolled bleeding does happen though couldn't we just give clotting factor? It's not like we would just stand by and watch a patient bleed out.

 

[rxlea]

We discussed this in class yesterday. The main issue I see aside from cost and lack of "reversal" agent, is the short expiration date (30 days after opening the bottle). This could be a problem, especially in patients who aren't 100% compliant. While you do have to consider overall cost to the industry (including the cost of the INR monitoring for warfarin), personally, I don't see it as much of an advantage. My professor wasn't exactly thrilled when I mentioned the cost in class and when I suggested lovenox he basically shot me down because "patients have to give themselves shots everyday". I didn't bring up the lack of the reversal agent but I think I will come Tuesday and see what he says. It is worth discussing, I think.

 

[rxlea]

The idea of course is you won't need it. If uncontrolled bleeding does happen though couldn't we just give clotting factor? It's not like we would just stand by and watch a patient bleed out.

What is the cost associated with giving a clotting factor?

 

[Praziquantel86]

What is the cost associated with giving a clotting factor?

Not to mention that there is no one "clotting factor". It's unclear which (if any) of the many clotting factors are the appropriate reversal agent for a dabigatran-induced bleed. Either way, they're all pretty darned expensive.

 

[PumpkinSmasher]

What is the cost associated with giving a clotting factor?

hahaha, extremely expensive.

 

[owlegrad]

What is the cost associated with giving a clotting factor?

Well if we are discussing dabigatran, I assume cost is not an issue. 😉


Really I was just trying to point out that the idea that there is no reversal agent has to be false - it is not as if we would be powerless to stop the bleeding. I am really curious how big a deal this whole reversal agent idea thing is - coumadin is the only anticoag with it's own special reversal agent, right? And even that is only because of the way it prevents clotting. Does enoxaparin or any of the others have their own special reversal agent? I think we are just so used to having one with coumadin that we think we need to have one for dabigatran as well - not really sure that is the case. I would love to hear counter arguments though.

 

[spacecowgirl]

hahaha, extremely expensive.

So much so, my little hospital doesn't even have it. So factor in the ambulance or worse, the chopper to take them to another site.

I think FFP is the tx of choice though.

 

[spacecowgirl]

Well if we are discussing dabigatran, I assume cost is not an issue. 😉

It is to the facility that has to stock it, grasshopper 😉

 

[owlegrad]

We discussed this in class yesterday. The main issue I see aside from cost and lack of "reversal" agent, is the short expiration date (30 days after opening the bottle). This could be a problem, especially in patients who aren't 100% compliant. While you do have to consider overall cost to the industry (including the cost of the INR monitoring for warfarin), personally, I don't see it as much of an advantage. My professor wasn't exactly thrilled when I mentioned the cost in class and when I suggested lovenox he basically shot me down because "patients have to give themselves shots everyday". I didn't bring up the lack of the reversal agent but I think I will come Tuesday and see what he says. It is worth discussing, I think.

Wow I did not know that. That's crazy! I haven't seen it yet, I take it that it comes to the pharmacy in bottles of thirty?

 

[rxlea]

Not to mention that there is no one "clotting factor". It's unclear which (if any) of the many clotting factors are the appropriate reversal agent for a dabigatran-induced bleed. Either way, they're all pretty darned expensive.

hahaha, extremely expensive.

Well if we are discussing dabigatran, I assume cost is not an issue. 😉


Really I was just trying to point out that the idea that there is no reversal agent has to be false - it is not as if we would be powerless to stop the bleeding. I am really curious how big a deal this whole reversal agent idea thing is - coumadin is the only anticoag with it's own special reversal agent, right? And even that is only because of the way it prevents clotting. Does enoxaparin or any of the others have their own special reversal agent? I think we are just so used to having one with coumadin that we think we need to have one for dabigatran as well - not really sure that is the case. I would love to hear counter arguments though.

So much so, my little hospital doesn't even have it. So factor in the ambulance or worse, the chopper to take them to another site.

I think FFP is the tx of choice though.

It is to the facility that has to stock it, grasshopper 😉

That was exactly my point.... we have many clotting factors where I work and they are SOOOOOOO expensive I can't even imagine what the total cost of treatment is for these patients. And yes, each one is for a different purpose. Every time I have to prepare one I think to myself, I might as well be holding a stack of hundred dollar bills in my hand... no room for mistakes!

 

[owlegrad]

It is to the facility that has to stock it, grasshopper 😉

Haha, you got me there.

Does anyone stock it yet? I mean I can see the advantage for the outpatient population (no monitoring), but I don't see any advantage for inpatient. It's just one more lab on top of everything else that is no doubt already being monitored.

 

[spacecowgirl]

I think it's up for formulary review really soon for us. I don't anticipate much use of it for awhile though, mainly due to cost and lack of familiarity.

 

[owlegrad]

So much so, my little hospital doesn't even have it. So factor in the ambulance or worse, the chopper to take them to another site.

I think FFP is the tx of choice though.

I would not have guessed that. OK though, so we give FFP. Has anyone out here had to do this to someone on dabigatran? The idea is you won't have to, right? Same as the other non-coumadin anticoags?

EDIT: Wait maybe I am being thick here, but is this just to restore volume? I mean it won't stop the bleeding will it?

 

[rxlea]

Well if we are discussing dabigatran, I assume cost is not an issue. 😉


Really I was just trying to point out that the idea that there is no reversal agent has to be false - it is not as if we would be powerless to stop the bleeding. I am really curious how big a deal this whole reversal agent idea thing is - coumadin is the only anticoag with it's own special reversal agent, right? And even that is only because of the way it prevents clotting. Does enoxaparin or any of the others have their own special reversal agent? I think we are just so used to having one with coumadin that we think we need to have one for dabigatran as well - not really sure that is the case. I would love to hear counter arguments though.

Our latest case study was on this....

EDIT: for lovenox, I think they use protamine but it's not as effective as it is with heparin.

 

[owlegrad]

That was exactly my point.... we have many clotting factors where I work and they are SOOOOOOO expensive I can't even imagine what the total cost of treatment is for these patients. And yes, each one is for a different purpose. Every time I have to prepare one I think to myself, I might as well be holding a stack of hundred dollar bills in my hand... no room for mistakes!

Funny stuff. I have only seen one patient on it and we had him bring it from home while he was with us ($$$). It was interesting though, because we used the same kits that he used (well we used his) and it had this cool "transfer needle" to use. Do you know what I am talking about? Kinda like a straw, sort of - it just had two needles connected together. Here's a pic:

It was definitely different than what we normally do. Fun in a way. Like you said, the expense was definitely something I was thinking about the whole time. Don't screw up, don't screw up, don't screw up....

 

[rxlea]

Funny stuff. I have only seen one patient on it and we had him bring it from home while he was with us ($$$). It was interesting though, because we used the same kits that he used (well we used his) and it had this cool "transfer needle" to use. Do you know what I am talking about? Kinda like a straw, sort of - it just had two needles connected together. Here's a pic:

It was definitely different than what we normally do. Fun in a way. Like you said, the expensive was definitely something I was thinking about the whole time. Don't screw up, don't screw up, don't screw up....

Yes, they all have those connectors. The ones we have sort of snap on so it would be pretty hard to eff it up unless you weren't paying attention or something.

 

[owlegrad]

Yes, they all have those connectors. The ones we have sort of snap on so it would be pretty hard to eff it up unless you weren't paying attention or something.

That sounds smart. His did not - it wasn't the sturdious connection I ever saw. It worked though and was pretty neat. Why the special needle though I wonder? I thought it was because he was bringing it from home, but if that is what your institution uses I guess their must be some reason? I mean why not just reconstitute the "normal" way (you know - regular needle with barrel)?

 

[rxlea]

That sounds smart. His did not - it wasn't the sturdious connection I ever saw. It worked though and was pretty neat. Why the special needle though I wonder? I thought it was because he was bringing it from home, but if that is what your institution uses I guess their must be some reason? I mean why not just reconstitute the "normal" way (you know - regular needle with barrel)?

That is a very good question... I never thought to look into it. I am thinking just to prevent error and decrease lost volume in transfer. Hell, I dunno. But, I didn't go to work this weekend so I can't look it up. Next week though I will take a look at the box/insert and see what it says.

 

[owlegrad]

That is a very good question... I never thought to look into it. I am thinking just to prevent error and decrease lost volume in transfer. Hell, I dunno. But, I didn't go to work this weekend so I can't look it up. Next week though I will take a look at the box/insert and see what it says.

I await your reply with baited breath.

 

[Praziquantel86]

Well if we are discussing dabigatran, I assume cost is not an issue. 😉


Really I was just trying to point out that the idea that there is no reversal agent has to be false - it is not as if we would be powerless to stop the bleeding. I am really curious how big a deal this whole reversal agent idea thing is - coumadin is the only anticoag with it's own special reversal agent, right? And even that is only because of the way it prevents clotting. Does enoxaparin or any of the others have their own special reversal agent? I think we are just so used to having one with coumadin that we think we need to have one for dabigatran as well - not really sure that is the case. I would love to hear counter arguments though.

Heparin and the low molecular weight heparins, to a certain extent, are reversible by protamine. Some of the more exotic anticoagulants may be effectively inactivated by platelets or simply short half-lives. The reason why dabigatran is such an issue is the unknown nature of it's reversal agent and the cost associated with some of the potential candidates.

I would not have guessed that. OK though, so we give FFP. Has anyone out here had to do this to someone on dabigatran? The idea is you won't have to, right? Same as the other non-coumadin anticoags?

EDIT: Wait maybe I am being thick here, but is this just to restore volume? I mean it won't stop the bleeding will it?

Yes, my relatively small institution has already had two major bleeds present after dabigatran use. One got FFP the other got Factor VII. Bleeding can, and does, happen on dabigatran. When you extrapolate those relatively small numbers seen in the studies to an entire population, you begin to see real-life cases. Less than those with warfarin, for sure, but still some. Without a clear reversal agent, these small numbers can become a major issue.

FFP would not be used for volume expansion alone (or even primarily). It contains all the active clotting factors found physiologically. You'll typically see it used in cases of large-volume crystalloid resuscitation (trauma, surgery, etc.) where these factors have been diluted enough to render a person coagulopathic.

 

[owlegrad]

Heparin and the low molecular weight heparins, to a certain extent, are reversible by protamine. Some of the more exotic anticoagulants may be effectively inactivated by platelets or simply short half-lives. The reason why dabigatran is such an issue is the unknown nature of it's reversal agent and the cost associated with some of the potential candidates.

Oh yeah. Thanks for reminding me, I forgot all about that. I have never seen it used, but I don't know why I wasn't thinking about it - I did learn about it in cology.

Thanks!