Tips for Safe Use of Allopurinol in Gout Save
Dr. Janet Pope, London, Ontario, offers tips for safe use of allopurinol.
Transcription
Hi, it's Dr. Janet Pope. I'm recording for RheumNow and you can certainly follow me as well at Janet Pope. We're talking a lot this recent past about gout. So I want to give you some Pope's tips for safe use of allopurinol prescribing in patients with gout.
So number one, if using allopurinol for gout, it is a forever medication for most patients. So be sure there's a good reason to prescribe it. The main indications are tophi, recurrent gout, greater than two attacks per year after trying lifestyle modification, medication modification, etc., and obviously chronic attacks, smoldering gout, joint damage on X-rays. There are other indications prior to chemo if you're going to have a huge breakdown of cells, or for uric acid stones, but I'm really talking about the rheumatology indications.
So number one, the traditional thinking is to go low and slow with allopurinol. Now, I sometimes like to go higher dose and faster, but I'll tell you why that could be wrong. If you go low and slow, you should reduce hypersensitivity reactions and possibly fewer initial gout flares. Although I often will give prophylaxis at the same time if my patient looks like they'll need it. So my problem is I know that my patient will take a long time to get to target and every time I increase the dose of allopurinol I'm going to give them more attacks and that doesn't really help adherence. However, there are some very reasonable data that hypersensitivity reactions and severe flares are more if you start fast. So start at 100 milligrams, reduce if there's CKD, keep following uric acid and go as high as needed getting uric acid to target.
The next thing is I usually wait about four to six weeks to redo the uric acid — so often six weeks — and then let the patient know to increase their dose or not. Flare prophylaxis might be needed. But at least one study shows that you can start allopurinol right away even if the patient's in an acute attack, but of course you would be treating the gout attack at the same time, the gout attack to end, and that's important if your patients have one attack after another.
Okay, what about other safety? So people from Southeast Asia have a higher risk of problems. By Southeast Asia I mean Han Chinese, Thai, Korean, amongst others. So they have more severe skin reactions — hypersensitivity reactions. So should they be tested for allopurinol safety if you're going to use it? Probably yes. Should everyone be tested? No. So the test that you order is HLA-B*58 and you're looking for 01 as the type of the HLA-B*58:01, and that should be considered prior to allopurinol use. If you can't afford it or can't get access to it, then you work your way up.
Another pearl that's important is the SGLT2 drugs, the inhibitors, can increase gout initially because they break down purine metabolism. So they work very much like allopurinol and when the drugs first came out, I noticed patients were getting gout and I didn't know why. And then eventually their uric acid was good and papers have been written about this — it's well described.
Now this is another important tip. Be aware of lupus and CKD patients, or chronic kidney disease patients with lupus, that could be from heart failure, from active or previous lupus nephritis, from interstitial nephritis, etc., or other reasons. And said use — we have to be aware that if I have a patient with lupus and they have CKD, beware: it is very bad to use azathioprine at full dose with allopurinol, unless you want to be sued and really harm your patient.
So what should you do? So I have had patients on azathioprine — if possible, when they have chronic tophaceous gout, I will stop azathioprine and see if they're going to flare or not, and I will stop before I start allopurinol. If you must use azathioprine you should go to about a quarter of the dose they are on — a 75% reduction of the current dose — and you must do at first frequent complete blood counts with a differential because of the cytopenias. Why does this happen? Allopurinol blocks xanthine oxidase, which is how azathioprine is metabolized.
A safer option is MMF. So I have read in some papers that MMF has less interaction with allopurinol, so it would be preferred over azathioprine, but even then use it with caution. And please follow guidelines, test your patient, and please discuss with a lupus patient with CKD who needs allopurinol — because CKD is a risk as well — about azathioprine and even about not starting it and being very careful.
So I hope these tips are helpful. Some of them are obvious and some of them might not be as well known for some of you. Thank you.
So number one, if using allopurinol for gout, it is a forever medication for most patients. So be sure there's a good reason to prescribe it. The main indications are tophi, recurrent gout, greater than two attacks per year after trying lifestyle modification, medication modification, etc., and obviously chronic attacks, smoldering gout, joint damage on X-rays. There are other indications prior to chemo if you're going to have a huge breakdown of cells, or for uric acid stones, but I'm really talking about the rheumatology indications.
So number one, the traditional thinking is to go low and slow with allopurinol. Now, I sometimes like to go higher dose and faster, but I'll tell you why that could be wrong. If you go low and slow, you should reduce hypersensitivity reactions and possibly fewer initial gout flares. Although I often will give prophylaxis at the same time if my patient looks like they'll need it. So my problem is I know that my patient will take a long time to get to target and every time I increase the dose of allopurinol I'm going to give them more attacks and that doesn't really help adherence. However, there are some very reasonable data that hypersensitivity reactions and severe flares are more if you start fast. So start at 100 milligrams, reduce if there's CKD, keep following uric acid and go as high as needed getting uric acid to target.
The next thing is I usually wait about four to six weeks to redo the uric acid — so often six weeks — and then let the patient know to increase their dose or not. Flare prophylaxis might be needed. But at least one study shows that you can start allopurinol right away even if the patient's in an acute attack, but of course you would be treating the gout attack at the same time, the gout attack to end, and that's important if your patients have one attack after another.
Okay, what about other safety? So people from Southeast Asia have a higher risk of problems. By Southeast Asia I mean Han Chinese, Thai, Korean, amongst others. So they have more severe skin reactions — hypersensitivity reactions. So should they be tested for allopurinol safety if you're going to use it? Probably yes. Should everyone be tested? No. So the test that you order is HLA-B*58 and you're looking for 01 as the type of the HLA-B*58:01, and that should be considered prior to allopurinol use. If you can't afford it or can't get access to it, then you work your way up.
Another pearl that's important is the SGLT2 drugs, the inhibitors, can increase gout initially because they break down purine metabolism. So they work very much like allopurinol and when the drugs first came out, I noticed patients were getting gout and I didn't know why. And then eventually their uric acid was good and papers have been written about this — it's well described.
Now this is another important tip. Be aware of lupus and CKD patients, or chronic kidney disease patients with lupus, that could be from heart failure, from active or previous lupus nephritis, from interstitial nephritis, etc., or other reasons. And said use — we have to be aware that if I have a patient with lupus and they have CKD, beware: it is very bad to use azathioprine at full dose with allopurinol, unless you want to be sued and really harm your patient.
So what should you do? So I have had patients on azathioprine — if possible, when they have chronic tophaceous gout, I will stop azathioprine and see if they're going to flare or not, and I will stop before I start allopurinol. If you must use azathioprine you should go to about a quarter of the dose they are on — a 75% reduction of the current dose — and you must do at first frequent complete blood counts with a differential because of the cytopenias. Why does this happen? Allopurinol blocks xanthine oxidase, which is how azathioprine is metabolized.
A safer option is MMF. So I have read in some papers that MMF has less interaction with allopurinol, so it would be preferred over azathioprine, but even then use it with caution. And please follow guidelines, test your patient, and please discuss with a lupus patient with CKD who needs allopurinol — because CKD is a risk as well — about azathioprine and even about not starting it and being very careful.
So I hope these tips are helpful. Some of them are obvious and some of them might not be as well known for some of you. Thank you.
If you are a health practitioner, you may Login/Register to comment.
Due to the nature of these comment forums, only health practitioners are allowed to comment at this time.