Anthony Perissinotti, PharmD, BCOP: When I have a patient that I’m worried about tumor lysis syndrome, whether it’s for prevention or treatment, I start everybody on allopurinol. I will start them on 300 mg twice a day at least initially for a day or two to load them up. Then I transition them to 300 mg daily. For patients that are at very high-risk or their uric acid is already quite high, I just continue them on 300 mg twice a day. This has been the standard of care since the 1960s. I usually continue it until I no longer feel that they are at risk for further tumor lysis. Usually this takes a couple days after they are complete of their chemotherapy. To make it easy sometimes I just tell our interns send our patient home with 7 days of allopurinol and that usually does the trick.

There’s another xanthine oxidase inhibitor, febuxostat, which is a little bit more potent than allopurinol. There was this trial, called the FLORENCE trial [NCT0172452], that showed febuxostat could lower uric acid a little bit quicker than allopurinol. There’s some debate about whether that is true or not, and whether it was just an underdosing of allopurinol. That being said, when I have a patient who I’m worried about their uric acid but I’m not quite worried enough that I want to pull out rasburicase, that’s a patient who I might consider using febuxostat. I use 120 mg daily and again, similar to allopurinol I start before chemotherapy and I continue it past the period of their risk.

As far as rasburicase, rasburicase has been studied in randomized controlled trial published in [the Journal of Clinical Oncology] by [Jorge] Cortes [, MD, Georgia Cancer Center] back in 2010, so we’ve had this data for quite a while. We’ve learned a lot of the use of rasburicase since this trial and one of the things we’ve learned is understanding that we can use fixed dosing. I typically will use 3 mg for most patients when their uric acid rises. I don’t use it for prophylaxis, I use it for treatment and I use it when I see the uric acid is inappropriately high. Many guidelines and many institutional practices use rasburicase the second they see the uric acid jump above 8 mg/dL, then they give rasburicase. I don’t usually use one laboratory value at one moment in time to decide on therapy. I’m a bit more methodical about it. I’m thinking about what’s the patients trends, what’s the patients risk, how much fluid have they received, how much fluid can I continue to give. It’s a lengthy thought process before just saying, “Oh the uric acid is 8 mg/dL I’m going to give rasburicase.” I typically watch the trends. There are levels of uric acid that I do say the uric acid is this and I automatically give rasburicase. Usually when their uric acid is above 15 mg/dL I don’t even think about it and I just give rasburicase.

It brings up a question that is admitted and their uric acid is, say, 20 mg/dL, so it’s at a very dangerous level that can lead to renal failure and the need for dialysis. It’s an open question of should you wait to give rasburicase and do G6pd deficiency testing, because patients can get hemoglobinemia. In my practice I don’t wait. If I have an emergency where I need to get the uric acid down immediately, I’ll give them a small dose, 3 mg or 6 mg, and I’ll monitor the patient very closely. Now if I have time, I certainly will consider G6pd deficiency testing in patients with Mediterranean decent or northern African descent. If they fit the phenotype, I’ll consider it if time allows, but if time doesn’t allow, I’ll give them rasburicase regardless of that testing. Again, my approach is probably a little bit more conservative than others. It really just comes down to the cost of the medication and also my comfort level with monitoring patients very closely and knowing that I can pull the trigger at any moment to get their uric acid down to essentially zero the second that I’m worried about the patient.

Another contentious debate among experts is, do you use rasburicase by itself, or can you combine it with a xanthine oxidase inhibitor like allopurinol? Part of the concern is that some believe that if you give allopurinol you’re going to increase hypoxanthine and xanthine and if you give rasburicase you’re going to continue to see very high levels of hypoxanthine and xanthine. Which can cause xanthine nephropathy. This is not a proven disorder so I am not worried about xanthine nephropathy, especially when I’m giving patients 200 ml/hour of normal saline. So to me it’s not a big issue.

The other thought is that some believe that giving the combination is just pointless because you are giving rasburicase. If the uric acid is going down to zero why do you even need more agents to reduce the uric acid or prevent the uric acid from going up. I think in the world of using fixed dosing, there are many patients who do require multiple doses of rasburicase. So at our institution, our thought process is to potentially to prevent additional need for giving more and more doses of rasburicase, because we probably are under-dosing some patients, if we use the combination we might be able to prevent the uric acid from rising again. Again, it’s a debate. I’d say if you ask one expert, they’ll say the combination is fine, you ask another expert and they’ll say absolutely not because you’re going to potentially increase their risk for renal failure.

Transcript edited for clarity.