QD 86 - Aravarama Save
QD Clinic - Lessons from the clinic
Tips on using Leflunomide
Features Dr. Jack Cush
YouTube Link: https://youtu.be/mLEFPYVl3vk
Transcription
Welcome to QD Clinic. QD Clinic is brought to you by rheumnow.live. I'm doctor Jack Cush, executive editor of rheumnow.com. Today's case is called Arrevorama. That means everything Arreva.
45 year old woman comes to clinic, previously treated with methotrexate, didn't like it, didn't respond to it, was put then on adalimumab. Kind of better, but not really. Still has polyarthritis with some swollen joints. She's kind of a failure, maybe a partial responder. And the question is, what do you do?
In discussions with the fellows on this case, it's we talked about, you know, what are the options. In a cost efficient world, you probably would have gone actually from methotrexate to combination DMAR, triple DMAR therapy, and then maybe a TNF inhibitor, and then maybe another TNF inhibitor, another non TNF biologic, or another JAK inhibitor. But somewhere along the line, the drug leflinamide has fallen off the menu, and that doesn't seem to make a lot of sense given how effective leflunomide is. Outside of North America, leflunomide may be the best selling DMARD worldwide. It works.
It works just like as well as methotrexate and seems to have a similar side effect profile, though my partner says methotrexate has side effects from here up, meaning from, like, the chest up, head, and sores, and leflunomide's got it from the chest down. I'm not sure it's quite that simple. A few things you should know about leflunomide. I I I was a non believer in leflunomide until I got involved in the leflunomide trials, and then I became a big believer. So maybe I've drunk the Kool Aid or maybe I have more experience using it, but it's a highly effective DMARD.
A few things you need to know, the main thing of course would be liver enzyme. Well, main thing would be the box warning on the package insert. The box warning says it's a teratogen shouldn't be used in people who want to get pregnant. Although there are reports of successful pregnancies in people who are on leflinamide. And people who are pregnant should undergo a drug washout procedure, we'll talk about that next.
And then it's hepatotoxicity is a is a warning. There are reports of threefold or higher elevations of LFTs are tenfold higher, but true hepatic cirrhosis, necrosis, death is really quite rare. When the FDA did an analysis of the hepatotoxicity of leflunomide, It was pretty much shown to be equal to that of methotrexate with looking at specifically at threefold or higher elevations of LFTs, especially AST, two to 4%, threefold or higher elevations ALT about one percent. So it's something that's quite manageable. You need to monitor and look for it.
The standard dose here is twenty milligrams a day. Forget the one hundred milligram loading dose that nobody uses that anymore. There is also a ten milligram pill. Generally, everybody should be on the twenty milligram pill unless they can't tolerate tolerate it, and then you can go to the ten milligram pill, or people are doing very, very well, can go from twenty to ten milligrams a day and usually maintain the efficacy once being used as monotherapy or as combination therapy. You should recognize the half life of leflunomide is really really long.
It's twenty one days. The primary metabolite, the M1 metabolite of leflunomide is a drug that's also market on, also on the market for, neurologic considerations and that's terraflunomide. Leflunomide not so expensive, the M1 metabolite, very expensive, It has to do with the indications, guess. But nonetheless, you're only gonna use leflinamide, but the long half life is an advantage that you can exploit, meaning people who've done well on leflinamide can be switched over to once a week leflinamide. I do it all the time with no loss of efficacy and no added toxicity.
I generally use twenty milligram pills and tell people they were taking twenty milligrams once a day. Most of them I switch to a hundred milligrams once a week. Some need a hundred and twenty milligrams or sixty milligrams once a week. You can titrate it depending on whether it's monotherapy or in combination. The package insert says that you should test for TB prior to or as you're using leflunomide.
There is a real risk of TB in people who are taking this drug. We know the intolerances and the side effects of this. GI toxicity, mainly in the form of cramping and diarrhea, about twenty percent of individuals. Somewhat bothersome and often often limiting as far as the use is either a ten percent risk of hair loss or ten percent risk of hypertension. After that, everything's really quite rare.
We talked about the, the long half life. You should know there are a number of drug interactions that you should be aware of. Because of cytochrome P450 activity, it will increase the dose of drugs like Xanaflex, Cymbalta, and Warfarin, so you have to watch those drugs. Taking rifampin will increase the dose of leflunomide, and patients who are taking rosuvastatin should not take dose higher than ten milligrams a day of rosuvastatin if they're on leflunomide. If you get into trouble with this drug, either extreme toxicity or pregnancy, the recommended procedure is eight grams, eight gram packets of cholestyramine three times a day times eleven days.
Now, if you're and that's for extreme stuff and you can actually measure drug levels and whatnot if you're really worried about pregnancy issues. I rarely have ever had to do that. I rarely actually ever use the 11 full dose elimination procedure. I often will use an abbreviated procedure, either four or eight grams, whatever the patient will tolerate, three times a day for five days. And doing that, can lower drug levels by more than 50%.
If you don't do an elimination procedure because of the long half life of the drug, it's gonna be in the patient's body for, I don't know, like nine years. It's really gonna be a long time. So to get it out, gotta do one of these elimination procedures. But an abbreviated regimen, again, TID times five days, drops levels by more than 50%, and that might be effective enough to reduce this toxicity the patient is worried about. Hypertension, diarrhea, mild to moderate elevations of LFTs.
These often respond well, and then either you can stop the drug or you can resume it at a lower dose. Arava is a very effective drug and should be used. You know, it's another very effective means of education is RheumNow Live. We're three days away. Check it out.
Go to roomnow.live and you can register. Make sure when you register, choose the online free registration, and then you can participate in the meeting starting on Friday afternoon, all day Saturday, half day Sunday morning. It's gonna be a great program. Registration is free for online access. Be there or be online.
It's gonna be a great meeting. That's it for this week, for this day of QD clinic.
45 year old woman comes to clinic, previously treated with methotrexate, didn't like it, didn't respond to it, was put then on adalimumab. Kind of better, but not really. Still has polyarthritis with some swollen joints. She's kind of a failure, maybe a partial responder. And the question is, what do you do?
In discussions with the fellows on this case, it's we talked about, you know, what are the options. In a cost efficient world, you probably would have gone actually from methotrexate to combination DMAR, triple DMAR therapy, and then maybe a TNF inhibitor, and then maybe another TNF inhibitor, another non TNF biologic, or another JAK inhibitor. But somewhere along the line, the drug leflinamide has fallen off the menu, and that doesn't seem to make a lot of sense given how effective leflunomide is. Outside of North America, leflunomide may be the best selling DMARD worldwide. It works.
It works just like as well as methotrexate and seems to have a similar side effect profile, though my partner says methotrexate has side effects from here up, meaning from, like, the chest up, head, and sores, and leflunomide's got it from the chest down. I'm not sure it's quite that simple. A few things you should know about leflunomide. I I I was a non believer in leflunomide until I got involved in the leflunomide trials, and then I became a big believer. So maybe I've drunk the Kool Aid or maybe I have more experience using it, but it's a highly effective DMARD.
A few things you need to know, the main thing of course would be liver enzyme. Well, main thing would be the box warning on the package insert. The box warning says it's a teratogen shouldn't be used in people who want to get pregnant. Although there are reports of successful pregnancies in people who are on leflinamide. And people who are pregnant should undergo a drug washout procedure, we'll talk about that next.
And then it's hepatotoxicity is a is a warning. There are reports of threefold or higher elevations of LFTs are tenfold higher, but true hepatic cirrhosis, necrosis, death is really quite rare. When the FDA did an analysis of the hepatotoxicity of leflunomide, It was pretty much shown to be equal to that of methotrexate with looking at specifically at threefold or higher elevations of LFTs, especially AST, two to 4%, threefold or higher elevations ALT about one percent. So it's something that's quite manageable. You need to monitor and look for it.
The standard dose here is twenty milligrams a day. Forget the one hundred milligram loading dose that nobody uses that anymore. There is also a ten milligram pill. Generally, everybody should be on the twenty milligram pill unless they can't tolerate tolerate it, and then you can go to the ten milligram pill, or people are doing very, very well, can go from twenty to ten milligrams a day and usually maintain the efficacy once being used as monotherapy or as combination therapy. You should recognize the half life of leflunomide is really really long.
It's twenty one days. The primary metabolite, the M1 metabolite of leflunomide is a drug that's also market on, also on the market for, neurologic considerations and that's terraflunomide. Leflunomide not so expensive, the M1 metabolite, very expensive, It has to do with the indications, guess. But nonetheless, you're only gonna use leflinamide, but the long half life is an advantage that you can exploit, meaning people who've done well on leflinamide can be switched over to once a week leflinamide. I do it all the time with no loss of efficacy and no added toxicity.
I generally use twenty milligram pills and tell people they were taking twenty milligrams once a day. Most of them I switch to a hundred milligrams once a week. Some need a hundred and twenty milligrams or sixty milligrams once a week. You can titrate it depending on whether it's monotherapy or in combination. The package insert says that you should test for TB prior to or as you're using leflunomide.
There is a real risk of TB in people who are taking this drug. We know the intolerances and the side effects of this. GI toxicity, mainly in the form of cramping and diarrhea, about twenty percent of individuals. Somewhat bothersome and often often limiting as far as the use is either a ten percent risk of hair loss or ten percent risk of hypertension. After that, everything's really quite rare.
We talked about the, the long half life. You should know there are a number of drug interactions that you should be aware of. Because of cytochrome P450 activity, it will increase the dose of drugs like Xanaflex, Cymbalta, and Warfarin, so you have to watch those drugs. Taking rifampin will increase the dose of leflunomide, and patients who are taking rosuvastatin should not take dose higher than ten milligrams a day of rosuvastatin if they're on leflunomide. If you get into trouble with this drug, either extreme toxicity or pregnancy, the recommended procedure is eight grams, eight gram packets of cholestyramine three times a day times eleven days.
Now, if you're and that's for extreme stuff and you can actually measure drug levels and whatnot if you're really worried about pregnancy issues. I rarely have ever had to do that. I rarely actually ever use the 11 full dose elimination procedure. I often will use an abbreviated procedure, either four or eight grams, whatever the patient will tolerate, three times a day for five days. And doing that, can lower drug levels by more than 50%.
If you don't do an elimination procedure because of the long half life of the drug, it's gonna be in the patient's body for, I don't know, like nine years. It's really gonna be a long time. So to get it out, gotta do one of these elimination procedures. But an abbreviated regimen, again, TID times five days, drops levels by more than 50%, and that might be effective enough to reduce this toxicity the patient is worried about. Hypertension, diarrhea, mild to moderate elevations of LFTs.
These often respond well, and then either you can stop the drug or you can resume it at a lower dose. Arava is a very effective drug and should be used. You know, it's another very effective means of education is RheumNow Live. We're three days away. Check it out.
Go to roomnow.live and you can register. Make sure when you register, choose the online free registration, and then you can participate in the meeting starting on Friday afternoon, all day Saturday, half day Sunday morning. It's gonna be a great program. Registration is free for online access. Be there or be online.
It's gonna be a great meeting. That's it for this week, for this day of QD clinic.
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