Taro warfarin question

[dick0236]

The spring of this year,2012, I switched to Taro warfarin(5mg tabs) for a weekly dose of 35mg. My INR, which had been consistantly in the 2.5-3.5 range, abruptly dropped into the 2.1-2.6 range beginning about 5 months ago and immediately after beginning Taro. Earlier this year, I had taken Zydus warfarin for 3 months (INR stayed between 2.7 and 2.9). Prior to this year, I had taken Barr Lab warfarin for over one year and INRs stayed 2.5-3.5, and usually 3+ to 3.5. Since moving from Coumadin, about 10-12 years ago, I have used Taro or Barr Labs warfarin interchangeabily over the years with little, or no, effect on INR. Anybody, especially Pharma. pros got any ideas why its happening now....there have been no lifestyle changes or any health issues(that I am aware of)

 

[Protimenow]

Interesting question, ****. I've taken warfarin from a various of manufacturers. I've usually run tests of my own just to make sure of bioequivalency. Usually, there's no effective difference.

Perhaps the batch of Taro warfarin, for some reason, was just not quite as accurately dosed as it should have been. I can't imagine any body - even yours - reacting differently to Taro than to other generics.

I'd probably try a newer batch of Taro warfarin and see if the change persists. (Then, too, our bodies change and occasionally respond more (or less) to warfarin. I know -- my dose has changed over the years).

 

[dick0236]

Interesting question, ****. I've taken warfarin from a various of manufacturers. I've usually run tests of my own just to make sure of bioequivalency. Usually, there's no effective difference.

Perhaps the batch of Taro warfarin, for some reason, was just not quite as accurately dosed as it should have been. ).

This has occured using two 90 day refills that where separated by ninety days. I thought the same thing, but the central Kroger Pharmacy fills a lot of Rx's and I doubt that both my refills came from the same batch. Like you, I have used these two brands interchangeably over several years, but have never experienced INR changes like this time.

 

[Bina]

****, If I remember correctly, member Freddie has had some INR changes that were possibly caused by a generic warfarin switch.

 

[Bill B]

You could write a Ph.D. thesis on this. Generic warfarin formulations are tested for "bioequivalence" to a standard but not to each other. There is a -20/+25% variation allowed from the standard in drug blood level area under the curve and peak. So, what this means is one product may be more bioavailable than the standard, but within the accepted range, while another could less bioavailable than the standard. The end result is that these two nonstandard products COULD be quite different from each other. And this can vary from lot to lot (but usually doesn't). So, this sounds like it could be a problem, doesn't it? In fact, there is little evidence of a real problem with warfarin despite the clear possibility. In published bioavailability analyses the differences between brands are much smaller than the allowed range. However, there are a few case reports of changes when patients were switched from one brand to another. There are numerous studies of populations of patients switched from one brand to another with no OVERALL change in INR results or clinical outcomes. However, buried within the data are some individual changes, in either direction. That's a bit hard to explain on the basis of bioavailability, except that there might be some individual factors that are not understood.

I prefer to stay with the same manufacturer for warfarin, but I have not seen any issue in my case.

http://www.fda.gov/downloads/Adviso...lScienceandClinicalPharmacology/UCM209319.pdf

http://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40301_Warfarin Sodium_Bioeqr.pdf

http://www.aapsj.org/abstracts/AM_1999/873.htm

http://www.ncbi.nlm.nih.gov/pubmed/11215837

http://www.ncbi.nlm.nih.gov/pubmed/15914517

http://www.bioline.org.br/pdf?ph04128

 

[Freddie]

****, If I remember correctly, member Freddie has had some INR changes that were possibly caused by a generic warfarin switch.

Holy Smokes! Bina has one heck of a memory.

I was taking Apo warfarin when my INR was dropping after being stable, only to find out (via Washington Post) that the manufacturer was shut down for a while due to cross contamination. I figured that I had one of last batches that were processed.

Since switching to Taro I've had no problems, but I am due for a refill soon. I wonder if the same scenario has happened again?

May I ask why you switched brands?

 

[dick0236]

I prefer to stay with the same manufacturer for warfarin, but I have not seen any issue in my case.

]

Thanks Bill, I knew I would get some expertise from a pharmacist. I have a pretty good record of my INR history dating back to the time I was still on Coumadin in 2002. I was always changing dosage in those days, primarily due to my Doc keeping me on a "yo-yo". I changed Docs and went onto generic Warfarin in 2005 and my INRs settled down. I have been on 35mg/wk since switching to Warfarin, with only a few minor adjustments, until recently. I started on Taro in 2006 and stayed with that brand until late 2010(I think). My pharmacy, Kroger, changed contracts and switched me to Barr Lab in Nov., 2010 and I had NO changes in my INR's which normally ran between 2.9 and 3.5......and I am very comfortable at the higher end of my range. In Dec., 2011, Kroger switched me to Zydus brand which made me uncomfortable, although my INR's stayed around 2.8 for the three month period I took that drug. I asked Kroger to switch me back to either Barr Lab(they would have to special order) or Taro(which they keep on hand). I switched to Taro in March 2012 and my INR's dropped immediately to the lo end, or below(2.1-2.6) my range, even with increases in dosage. I think I am going back to Barr Lab, although it will take me a little time to get my INR sorted out now that I have begun to adjust my dose to Taro.

Freddie...I switched due to my pharmacy changing suppliers and I didn't think that brand changes would have an effect on my INR. I think after I get this sorted out, I will stay with one brand.....it is a little "pain in the A--" to continuosly re-regulate warfarin.

 

[dick0236]

Thanks for the input. I have decided to go back to the Barr Lab brand, and it may take me a month, or so, dammit, to re-adjust to my 2.5-3.5 INR using Barr brand. Hopefully, I will quickly get back to my steady 5mg/day that I enjoyed for the last several years.

This blows the hell outa my thought that warfarin brands are easily interchangeable....at least for me. I have spoken with a couple of local pharmacists and they agree with Bill B......it is best to stay with the same brand to avoid disruptions.

I do know that there have been no life issues, lifestyle changes, diet, etc., etc., that should have caused an INR drop....so it must be the Taro pill???

I guess there could be a medical issue, with me, that I am not aware of, that could be causing an INR problem....and I'll ask my Doc about that.

 

[Protimenow]

It's probably safe to assume that different batches of a particular brand's warfarin would have the same biological effect -- but if the standard is loose, as Bill describes it, it's possible that there may be variances from lot to lot of the same brands.

This is another reason why I believe in self-testing -- and why I try to do so every week -- unless I detect a drop or spike in my INR or have made some kind of change. It's good to be on top of things -- as long as any changes are minimal and gradual -- or according to some established protocols.

 

[Cooker]

A customer of ours is a pharmaceutical-rep and she was telling me that the active ingredient in any generic can deviate as much as 20% and still be within FDA guidelines .... don't know if it's true but she had no agenda with me....

 

[dick0236]

A customer of ours is a pharmaceutical-rep and she was telling me that the active ingredient in any generic can deviate as much as 20% and still be within FDA guidelines .... don't know if it's true but she had no agenda with me....

Thanks Cooker. That's pretty much what Bill B posted earlier and is what my PCP told me. I thought that claim was propaganda put out by Brisol Myers, but maybe not. I'm going back on Barr Lab and we'll see what happens. It's strange, because I was on Taro before and did not have a problem maintaining a 3+ INR on 5mg/day. Nor did I have any INR changes when I switched from 5/mg Taro to 5/mg Barr about 1-1/2 years ago. I'll let ya'll know what happens.

 

[Protimenow]

FWIW -- when I was getting my warfarin from a pharmacy in India (before I was able to get it for about the same price here), I had no problems with the Taro that they sent me. The dire cautions about foreign meds, from my experience, are way overblown -- if the rest of the world takes the same medications why would pharmaceutical companies intentionally want to produce lower quality drugs?

(No - I don't mean to change the subject of this thread, so no response to this one is needed).

 

[Superman]

I was switched to Taro from my old manufacturer and found that I was able to decrease my dose by 3mg per week. I'd have to look up the name of the old one. Most of it is cost driven so it's not easy to shop around pharmacies and find a particular generic manufacturer.

 

[catwoman]

I've used Coumadin and Barr, Taro & Zydus. Never had a problem, other than the occasional blip that could be resulting from erratic schedule when traveling (time changes, forgotten dosage & having to compensate for it, etc.). Because I split the tabs, I like some pill shapes better than others; Coumadin's round shape is at the bottom of my list for that reason (in addition to price).

 

[Bill B]

Thanks Cooker. That's pretty much what Bill B posted earlier and is what my PCP told me. I thought that claim was propaganda put out by Brisol Myers, but maybe not..

I provided a link to a presentation given by FDA staff that confirms the range allowed (-20 to +25%). It is a point of controversy. Warfarin is considered a "narrow therapeutic range" drug, and that variation range is still considered safe by the FDA.

 

[dick0236]

I provided a link to a presentation given by FDA staff that confirms the range allowed (-20 to +25%). It is a point of controversy. Warfarin is considered a "narrow therapeutic range" drug, and that variation range is still considered safe by the FDA.

I interpret this to mean a 5mg Rx could actually vary from 4mg to 6.25mg between brands??
That seems to be an awfully wide spread. No wonder frequent testing is necessary....especially if you take whatever brand the pharmacy has on hand.

 

[Jkm7]

Can't you request the pharmacy always get you the same generic rather than going from one brand to another? If not, how about going to a different pharmacy that will get your brand for you?

 

[Bill B]

I interpret this to mean a 5mg Rx could actually vary from 4mg to 6.25mg between brands??
That seems to be an awfully wide spread. No wonder frequent testing is necessary....especially if you take whatever brand the pharmacy has on hand.

That is the standard. It has been that way since the late 90s. I re-checked it when you asked to make sure it hasn't changed. The FDA is basically saying that any change in response seen with that potential variation is not clinically significant. This has come under fire since the day it came out. Studies have not shown a problem in populations of patients who have been switched from one brand to another. Perhaps the saving grace has been that the US sources for these products have stayed within much tighter tolerances. That's what I have seen - they are within 5%. BUT, the criticisms that note the potential problem caused by the wide leeway in bioequivalence standards stand. One of my professors from the pharmacy school I went to was on a panel that made recommendations for improvements to the FDA's bioequivalence standards, but they were not implemented.

 

[Gail in Ca]

I know you can request a specific brand of generic for your warfarin. Most pharmacies can accomodate this if you give them time to order it before you need it. I am taking 7.5mg Barr and 10mg Taro right now, I don't specify brand and I just take what I get at cheapo Walmart pharmacy! But, I bet if I just wanted Barr, they would give it to me. I remember when I worked for Longs pharmacy, people would ask the difference between the generic and the name brand and the pharmacist would tell them that the bonding agent is different, but the active ingredient is the same strength.The body utilized it the same. That was many years ago!! We know alot more now about our drugs, don't we?

 

[Freddie]

The spring of this year,2012, I switched to Taro warfarin(5mg tabs) for a weekly dose of 35mg. My INR, which had been consistantly in the 2.5-3.5 range, abruptly dropped into the 2.1-2.6 range beginning about 5 months ago and immediately after beginning Taro. Earlier this year, I had taken Zydus warfarin for 3 months (INR stayed between 2.7 and 2.9). Prior to this year, I had taken Barr Lab warfarin for over one year and INRs stayed 2.5-3.5, and usually 3+ to 3.5. Since moving from Coumadin, about 10-12 years ago, I have used Taro or Barr Labs warfarin interchangeabily over the years with little, or no, effect on INR. Anybody, especially Pharma. pros got any ideas why its happening now....there have been no lifestyle changes or any health issues(that I am aware of)

Oh Boy. I did mention I was due for a refill and it looks like the same thing has happened to me ****. Can't find any issued recalls. Maybe someone can dig a little on the internet, I can't find anything.