Switching from Warfarin to Coumadin

[hannahsmom]

Good morning,

Hannah's INR has recently been all over the place. We have been working closing with her Cardiologist and assigned nurse to try and get her stable again (she was for 3 years). We have had her INR drop as low as 1.2 and then be as high as 4 the following week. She originally was on 6.5 mg of Warfarin daily, then she needed an increase to 7 last summer. Now she is on been moved all over the place as her INR is fluctuating so much. This of course results in very frequent testing requirements. Our most recent conversation with the Dr. and nurse resulted in them switching her to Coumadin to see if we can get the INR to stabilize.

My questions are:

Has anyone experienced this? Being stable and therapeutic for a long period of time, only for you INR to then go haywire for no apparent reason?
- She has had no substantial changes in diet, exercise, time of day she takes it, etc.

Has anyone changed from Warfarin to Coumadin and had better or worse results?
- I read some other forums online where patients were stating they more stable and consistent with Coumadin. Just curious if members here agree?

She is at an age where everything is changing for her (hormones, body, lifestyle, etc) and I know there is not really any proof that this effects INR or sensitivity to medication, but it seems when she started to go through puberty is when we started having various INR readings. Any input?

Thanks in advance for any experiences or information you have to share!

Kelly

 

[dick0236]

My questions are:

Has anyone experienced this? Being stable and therapeutic for a long period of time, only for you INR to then go haywire for no apparent reason?
- She has had no substantial changes in diet, exercise, time of day she takes it, etc.

Has anyone changed from Warfarin to Coumadin and had better or worse results?
- I read some other forums online where patients were stating they more stable and consistent with Coumadin. Just curious if members here agree?



Kelly

Hi Kelly

Yes, I have had INR seem to "go out of range for no apparent reason". Often, my "INR managers", complicate these periods by making dosing changes that put me on a yo-yo. Most recently, I was getting Rx refills from different warfarin manufacturers and that seemed to complicate staying in range....especially a brand(can't remember name) that came from India. I now use only one brand(Barr Labs) and the problem has been minimized. Even with generic warfarin I think it is best to stay with one brand.....because FDA standards allow for some tolerances between manufacturers. This is my opinion only, but my druggist agrees with me.

I have also heard that going on Coumadin from warfarin makes INR easier to manage. I switched to warfarin after 35+ years on Coumadin and found that I did better on warfarin.....go figure.

It would not surprise me if the "body changes" and lifestyle are having an effect on her INR. As a young man I took 70mg/wk but that has decreased to my current 35-38mg/wk.

Hang in there.

 

[pellicle]

Hi there

pardon me for venturing, as I do not have experience in moving from the brand Coumadin to another brand, but as you mentioned Warfarin (a more chemical name for the compound) and Coumadin (which is a brand that makes that drug) I thought that perhaps I could offer something.

Good morning,

Hannah's INR has recently been all over the place. We have been working closing with her Cardiologist and assigned nurse to try and get her stable again (she was for 3 years).

so, in the time when she has been having her INR all over the place, have you been 'rock steady' with the dose or has advice been to move the dose all over the place too?

you know, drop 50% for a day, drop a dose .. that sort of thing. Because if it has I would say that this has been the cause of the issue.

NB INR mismanagement. I had similar problems when I was with a lab and following their directions. Made a few mistakes myself too ... learned lots.

We have had her INR drop as low as 1.2 and then be as high as 4

I agree that 1.2 for any length of time is undesirable, but 4 is not threatening. There are natural variances and fooling around with the dose will often exaggerate them.

She originally was on 6.5 mg of Warfarin daily, then she needed an increase to 7 last summer. Now she is on been moved all over the place as her INR is fluctuating so much.

yep

This of course results in very frequent testing requirements.

how frequent?

do you have an INR meter? If not I strongly suggest you get one and test weekly ... even if you have to just pay for it yourself they are not that dear.

I test weekly. Here are my last years results.

Please note in the graph about week 25 I altered my dose significantly and it resulted in a plumet. The lowering at week 15 through 17 was as a result of a hospital visit (and arguments with a professional).

You can see also that from week 29 on while my INR varied it was within the INR range of 2.2 ~ 3 (which is the range specified by my surgeon).

when at week 37 it was trending higher (and I mean over a few weeks) I dropped my dose by a very small amount 7.25 daily to 7 daily. Not a big change. My INR value trended downwards (as can be seen in the moving average) and I decided to up it to 7.1mg daily (which is a pattern of 7.25 - 7 - 7 - 7.25) where my trend is not more stable

Our most recent conversation with the Dr. and nurse resulted in them switching her to Coumadin to see if we can get the INR to stabilize.

I doubt it will stabilise without a steady hand on the tiller, however there may be some merit in changing brands due to different mixes of isomeric forms of Warfarin (they process differently) between brands.

but ... I'd focus on steady "as she goes" and not over react on the dose changes.

She is at an age where everything is changing for her (hormones, body, lifestyle, etc) and I know there is not really any proof that this effects INR or sensitivity to medication, but it seems when she started to go through puberty is when we started having various INR readings. Any input?

that does alter the equation, my responce to exersize alters my INR and I'm late 40's, perhaps there is something going on metabolically?

I strongly suggest move to weekly testing (buy a meter if needed) and make SMALL changes in dose. The meters can be had on eBay (often unused because gran didn't want to use it) and supplies had online for small amounts, typically $140 for 48 test strips. With weekly testing that's less than $200 per year.

I hope someone provides you another slant on this to give you alternative views

as to herbal remedies, well I just posted my results here showing that changing from supply in Finland (where I am now) from the supply I was using in Australia had no effect. This is because pharmaceutical companies are very tight on manufacturing tolerances. You just won't find that in 'herbal remedies' ... meaning expect a greater roller coaster "over there" ...



Best wishes

 

[Stopper]

Generic warfarin is allowed a certain variability by the FDA, so a 5mg dose might have a variability range of 15% (not sure what the exact percentage is). So this means that a 5mg dose might be a little more potent in one batch, and less potent in the next batch. Also there is variability between manufacturers of warfarin. Coumadin is manufactured by Bristol-Myers Squibb only, and is consistent with every patch that is produced. Being on Coumadin should help with consistency in dose, therefore giving you a better chance to stay within the therapeutic range.

 

[pellicle]

Generic warfarin is allowed a certain variability by the FDA, so a 5mg dose might have a variability range of 15% (not sure what the exact percentage is)

wow ... really? Thats huge!

Well anyway my brand is Marevan.

Studies I have read suggest many have no observable changes in INR moving between brands. If there is a difference between brands I feel it is most likely to be in the variations in isomers (mirror images of the same chemical formula)

 

[lance]

hello Hannahsmom,
Sorry, double post.

 

[lance]

hello Hannahsmom,
I had taken generic (same brand) warfarin for about 5 years without incident. Then INR levels became erratic. In spite of excellent management response to dose changes became bizarre--they made no sense. We tried for two months without success. In desperation we turned to brand name Coumadin and I was back in range within a week and still am. This happened over a year ago.
There is no explanation for what happened, everything else was the same.
So I feel some generics should be avoided.

 

[pellicle]

out of interest I did a little digging.

http://www.ncbi.nlm.nih.gov/pubmed/19776300
Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration.

RESULTS:The mean +/- SD of the GMRs from the 2070 studies was 1.00 +/- 0.06 for C(max) and 1.00 +/- 0.04 for AUC. The average difference in C(max) and AUC between generic and innovator products was 4.35% and 3.56%, respectively. In addition, in nearly 98% of the bioequivalence studies conducted during this period, the generic product AUC differed from that of the innovator product by less than 10%.

my reading on this is that 10% variance is to be expected, in some specific cases perhaps more (as that would not effect the average).

So my view would be to go with a good brand name that you trust. In the USA that would probably be Coumadin and here in Europe that would be Marevan.

Essentially I'm saying that I'm in favor of trying a "known brand", and if you get better results - stick to it ;-)

 

[lance]

Pellicle
That could be part of the reason. The dose responses I experienced were bizarre. When I tested at 2.6, added an extra 1 mg of Taro, tested 4 days later at 8--now that's bizarre! So I was out of range but not in a consistent way.

 

[pellicle]

Pardon me, but whats Taro?

 

[lance]

Pardon me, but whats Taro?

Taro is a generic a generic warfarin.

 

[pellicle]

Pellicle
That could be part of the reason. The dose responses I experienced were bizarre.

ok, well let me put forward a theory. So, here is my theory (ahhhh hem).

Metabolism is not perfectly even. So I submit that just as some days we feel better than others that on some days we process stuff in our bodies differently to other days. An example of this that is understood by (and accepted by) science are infradian rythms This can have an effect on our INR. So lets assume two scenarios for our "person"
1) very even dose of alternating 5/5.5mg daily (giving 37mg over the week)
2) a less even dose of 5, 5 and then 7.5mg in a repearing pattern (giving 39mg over the week)

In my INR model I've taken the approach of an accumulation of the drug in the body according to the known half life of the drug, and then added a 'metabolism' factor which is variant. I put a 'variation' in metabolism to drop down a little and to raise up a little. I deliberately timed my frequency to be different so that it will eventually fall on a worst case or a best case for an INR outcome. So lets look at the modeled INR for 1) on that

So what we see is that in some occasions a very high INR transient spike can emerge. Should you test on that day you'd see it ... if you didn't then (as the graph suggests) you'd not see it.

With a more even dose of 5 / 5.5 we see this:

where the spike is significantly lower. This supports why an even daily dose is important, as I have seen people doing stuff like 5mg except Wednesday when they take 10 (no joke) because they think in weekly dose averages and monthly testing.

Also my chosen metabolic variance is not very high, averaging 5.4 with Max of 6 and Min of 3 ... so if for some reason you're metabolism 'factor' varied more or had a longer period (for whatever reason) then you may see spikes go higher and last longer. For example (please also note the change in right hand AXIS scale to accommodate the spike that now goes to 8)

If your 'metabolism' remained suppressed longer (for some reason), then the duration of the INR spike would of course be longer.

I have seen evidence of this in my own INR measurement and also in the experiment on himself conducted by Ola (here)

his own results revealed a 'spike' (diagram below)

which conforms quite well to the cyclic metabolism factor that I included into my own model.

Please note: this model can not be used to predict INR, it is only intended to explore 'what if' scenarios. This is a simple model which is intended to illustrate a point. More sophisticated models may be more accurate, but for sure will need more tuning to each individual and may in turn give more inaccurate results due to that requirement.

 

[lance]

Thank you for your very thoughtful, expert explanation.
So it would seem metabolism was the same for more than 5 years, took a turn for about 2 months, turned back to what it was and has behaved itself ever since.
The 1 mg spike wasn't consistent with other erratic, bizarre INR responses to a dose adjustment just the worst one that I remember.
I think it significant though that INR's straightened out with the change to Coumadin.
It's an interesting discussion.
I hope our input helps Hannahsmom.

 

[pellicle]

So it would seem metabolism was the same for more than 5 years, took a turn for about 2 months, turned back to what it was and has behaved itself ever since.

Well your situation could be an alternative explanation to that above, it could be something else non cyclic that effected your metabolism.

Anyway I'm no expert, just an ex biochemistry dweeb who thinks too much.

 

[Lynlw]

Thank you for your very thoughtful, expert explanation.
So it would seem metabolism was the same for more than 5 years, took a turn for about 2 months, turned back to what it was and has behaved itself ever since.
The 1 mg spike wasn't consistent with other erratic, bizarre INR responses to a dose adjustment just the worst one that I remember.
I think it significant though that INR's straightened out with the change to Coumadin.
It's an interesting discussion.
I hope our input helps Hannahsmom.

Hey Lance, I just realised this month is a DECADE that you've been home testing. I think it is great you have stayed around sooo long to share what you have learned in that time and help so many others, Thank You. By the way what was it Rain used to say about INR going all over for no apparent reason? The dog was in the flower beds was the blame? Well that and i always think of the saying It's Never Right Anyway sorry to hijack thread just wanted to say thanks and hope I am still around to congradlalte you on 20 years.

Kelly, Hopefully brand name Coum will help settle things down, I remember over the years here other people finding problems w/ different brands etc.
I was thinking maybe it would be helpful to check out some of the CHD groups to see if other parents can help with their experience w/ children, especially females Hannahs age and growing, going thru puberty etc I would think it would all play a part in needing different amounts. Kids w/ CHD are on Coumadin for a few differnt reason beside mech valves so there are probably a lot of moms who can share their experience...and dads, but Moms are much more active for the most part.

Im glad to hear things are going well beside that, i cant believe is been 3 years already

 

[tom in MO]

My INR goes all over the place when I change my activity or are under stress. You may just be dealing with teen age body chemistry, angst and hyper activity followed by hyper laziness.

 

[hannahsmom]

Hello,

Thank you everyone for the information and experiences! Even her anticoagulation nurse who I love cannot give this kind of insight, so again thank you.

We are currently on weekly checks at the lab - thankfully the lab is two mins from our house. This child refuses to have her finger pricked, of all things... The dose changes have been slight each time she fluctuates however there have been times that she has fallen far out of range which then requires us to bridge or drastically reducing for safety purposes. Her attitude through all of this is admirable to say the least. She is such a trooper. Especially when lovenox was needed.

On 1/17 on Warfarin she had shot up to 5.6 from 3.7 the week before - last week on warfarin. Skipped 1/17's dose (she takes at night)
On 1/24 on Coumadin since 1/18 INR was 5. Skipped 1/24's dose. Slightly reduced weekly mg total.

She is getting checked again today. I should have her results tomorrow morning, so I will keep all of you posted on what she ends up at. I am sure they will require another check next week regardless of what it is.

Hopefully we can gradually get her back down. The drastic spiking up and down she has been experiencing makes me uneasy.

Thanks again for all of your support! You guys are awesome

 

[Lynlw]

Hello,

Thank you everyone for the information and experiences! Even her anticoagulation nurse who I love cannot give this kind of insight, so again thank you.

We are currently on weekly checks at the lab - thankfully the lab is two mins from our house. This child refuses to have her finger pricked, of all things... The dose changes have been slight each time she fluctuates however there have been times that she has fallen far out of range which then requires us to bridge or drastically reducing for safety purposes. Her attitude through all of this is admirable to say the least. She is such a trooper. Especially when lovenox was needed.

On 1/17 on Warfarin she had shot up to 5.6 from 3.7 the week before - last week on warfarin. Skipped 1/17's dose (she takes at night)
On 1/24 on Coumadin since 1/18 INR was 5. Skipped 1/24's dose. Slightly reduced weekly mg total.

She is getting checked again today. I should have her results tomorrow morning, so I will keep all of you posted on what she ends up at. I am sure they will require another check next week regardless of what it is.

Hopefully we can gradually get her back down. The drastic spiking up and down she has been experiencing makes me uneasy.

Thanks again for all of your support! You guys are awesome

Is it possible to list wha she took in a coloumn for the last month or so w/ the INR next to it? seeing it like that may make it easier to see whats going on and maybe help find a sweet spot. It is harder to give advice, or see what the problem is, especially when she was so high she had to skip doses more than once, which of course can set you up for the dreaded yoyo.
hopefully the slightly lower weekly using Coumadin like she is, will work well, but just incase it might help to see the fuller picture.. Ill see if I can find a post like Im talking abou



FWIW Luckily Justin isnt on any anticoags (or meds) but when he has had choices he prefers to be stuck in the arm vs finger pokes too, (unless they want to draw blood from back of hand, then he says fingerstick if possible) I've often thought it seems kids who have been in and out of he hospitals growing up either really HATE bloodwork , or don't mind much at all, unless they get to the point where it is harder and harder to find good veins.. I feel for Hannah w/ the Lovenox shots, I know they are usually quite painful and everyone would prefer not to need. She has always been such a trooper, I know you are very proud of her and should be.

 

[Protimenow]

What I have to offer may not be of much ultimate value, but here goes, anyway.
When I saw the beginning of your original comment, I thought 'what's wrong with this person's liver?' Then I realized that this was an adolescent girl, and it seemed to me that just the processes going on in her body can probably be having an effect on the way that warfarin (or coumadin - I don't know that it matters much whether you use patent or generic) is metabolized.

The suggestion that you try and see what others with children of the same age range, who are taking warfarin, have experienced may be helpful. I'm thinking that it may be a while before you can really get a good handle on stabilizing her INR. For my money, I would feel more comfortable with an INR at the high end of the range than I would having a daughter with an INR at the low end.

I concur with the suggestions that testing (and MINOR dose adjusting) be done weekly. It also makes sense to try and have her take the SAME dose every day (rather than the 5 on one day and 7.5 on another that I once did). That way, the INR SHOULD be relatively stable no matter which day you test it.

The metabolic variables that Pellicle brought up may be largely responsible for much of the fluctuation - I'm not sure how much of these factors can be controlled.

(Just a thought -- and perhaps someone can back me up on this -- the meters use capillary blood. I wonder if those capillaries HAVE to be on the fingers, or if they can be somewhere else - perhaps the heel? Are there other areas that can provide an adequate drop of blood for testing while being different enough from a fingerstick so that they are acceptable to people who dread having a poke in their fingers?)

 

[kpearse]

I've only taken warfarin for the last 6 years. My INR was all over the place. They would increase then decrease my dose. I think I've read most of the posts on home testing and thought they "over did" the dosing. Since I've been home testing I have been in range with just a little movement up and down, but in range! I hope it stays that way.