Warfarin vs Coumadin concentration

pem · Jul 30, 2014

Hi all. My INR recently spiked to 5.2. I couldn't figure out why. Then I remembered that I recently switched out some of my Coumadin with Warfarin because the insurance company no longer covers Coumadin.

So I did a little digging and found this article and this FDA publication.

I had heard that the tolerances for generic drugs are lenient but did not realize how lenient. It turns out that Warfarin can be only 80% as concentrated as Coumadin or as much as 125% as concentrated. This means that if I take 10mg/day (which is actually close to what I take) and then switch to Warfarin, it is conceivable that I am getting the equivalent of as little as 8mg of Coumadin or as much as 12.5mg of Coumadin. And it isn't clear if the Warfarin concentration can change over time without notice (does anyone know?) or if it's different from one generic version of warfarin to another.

So I guess if I have actually been taking 2mg more a day than usual due to switching to Warfarin that could explain my INR spike!

Wow. You'd think the tolerances would be tighter for drugs that have such a narrow therapeutic range.

chaconne · Jul 30, 2014

pem,

I've been taking Taro Warfarin for almost 3 years. For most of that time my dose has been the same. My guess is, for a given brand, the actual dose is consistent and doesn't vary over time.

pellicle · Jul 30, 2014

Hi

pem said:
Hi all. My INR recently spiked to 5.2. I couldn't figure out why. Then I remembered that I recently switched out some of my Coumadin with Warfarin because the insurance company no longer covers Coumadin.

I'm a little confused, Coumadin is just a brand name and Warfarin is a chemical compound, so Coumadin is Warfarin. Are you saying you've changed brand?

http://en.wikipedia.org/wiki/Warfarin

Warfarin (also known by the brand names Coumadin, Jantoven, Marevan, Uniwarfin)

There may be differences between brands, particularly in the mix of L and R Anomers (recalling stereochemistry here anomers or isomers are essentially mirror images of each other) and that the different Anomers of Warfarin (the chemical) are processed differently by the body, require different enzymes to breakdown and effect the INR differently.

Wow. You'd think the tolerances would be tighter for drugs that have such a narrow therapeutic range.

there is the tolerances generally and then there is the tolerances that any given manufacturer produces. I've found that Marevan (the brand I use) purchased in Australia had no change to my INR to the Marevan I bought in Finland (and which was manufactured in different locations based on the bottle).

Generally the advice is do not switch between brands without testing. Expect changes

dick0236 · Jul 30, 2014

Although I had no trouble switching from Coumadin to warfarin several years ago, I had a similar experience to yours a couple years ago when a pharmacy filled my warfarin Rx with tabs from a new lab I was not familiar with and my INR went a little haywire. Once you get regulated using one mfg., stay with that mfg. My current pharmacy has noted in my file that only Barr Lab warfarin is to be used for me......and it has made a difference. I am familiar with two labs that have offered good consistant quality warfarin in the USA for many years......Barr Lab and Tara Lab.

pellicle · Jul 30, 2014

PS: according to MIMS

Marevan is a raceminc mix of R and S enantiomers. The S-enantiomer exhibits 2 to 5 times more anticoagulation effect than the R-enantiomer in humans, but generally has a more rapid clearance.

so if even the mix of R and S enantiomers varies between brands you'll have an effect on anticoagulation.

So don't switch brands frequently

Protimenow · Jul 30, 2014

When I switched to generic, I also did some daily testing to see if there was any effect on my INR. Perhaps I've been lucky, but whichever generic that I've used, the effects were consistent. The FDA is pretty careful about bioequivalence, so I would not be particularly concerned by any brand. But, in the words of Ronald Reagan -- 'trust, but verify.' If you switch to a new manufacturer's warfarin, it wouldn't hurt (other than the cost of the strips) to test every few days for the first week or so on the new supply.