Urate-lowering Therapy: Adverse Effects and Contraindications (Nursing)

00:00 Now let's move on to a discussion of the adverse effects with urate lowering therapies used in the treatment of gout.

00:07 So allopurinol has some common adverse effects like rash and gastrointestinal upset, but there's more serious concerns, including hypersensitivity reactions, which are significantly more common in patients who have the HLA-B5801 allele.

00:24 Now this genetic variant is more prevalent in Asian and African American populations.

00:28 That's why there's a recommendation for them to have genetic testing.

00:32 Now a particularly severe reaction is the DRESS syndrome, drug reaction with eosinophilia and systemic symptoms.

00:39 Now we'll discuss that in more detail in just a minute.

00:42 There's also other serious adverse effects, including hepatotoxicity and bone marrow suppression.

00:49 Now with Febuxostat, it's commonly can cause liver enzyme elevations and nausea for your patients.

00:55 Now the biggest concern is its FDA black box warning, because this warning is regarding increased risk of cardiovascular death and all cause mortality compared to allopurinol.

01:07 Now let's break that down a little bit.

01:09 In this context, all cause mortality refers to death from any cause, regardless of the specific reason.

01:16 Now this FDA black box warning for Febuxostat indicates that clinical trials found an increased risk of death not only from cardiovascular causes specifically, but also an increased risk of death overall from any cause when you compare it to patients taking allopurinol.

01:31 This is why Febuxostat is typically reserved for patients who cannot tolerate allopurinol or in whom allopurinol is contraindicated, such as those who have test positive for the HLA-B5801.

01:44 Now all cause mortality is an important safety metric and this is why we use it, because it captures the total impact on survival, including both expected and unexpected causes of death.

01:55 Now it helps us prevent missing important safety signals that might be obscured if we just looked at specific causes of death.

02:01 This will help us account for potential misclassifications of cause of death and basically it represents the overall safety profile of the medication.

02:11 Now with Febuxostat, the risk is highest in patients with established cardiovascular disease.

02:16 Based on the 2019 FDA label update, Febuxostat should be reserved for patients who have failed or just cannot tolerate allopurinol, because those hypersensitivity reactions can occur but are less common with Hebexistat than with allopurinol.

02:33 Probenicid's common side effects include things like GI upset, headache, and flushing.

02:37 But there are some more serious concerns, things like nephrolithiasis or kidney stones.

02:42 That's due to the increased urinary uric acid.

02:45 We're also concerned about hypersensitivity reactions and the potential for uric acid nephropathy damage to the kidneys if the patients aren't adequately hydrated.

02:55 Now to prevent these complications, remember patients should maintain a high fluid intake of two to three liters daily while taking Probenicid.

03:02 Now here's some more about Probenicid.

03:04 It has significant drug interaction potential.

03:07 The reason is Probenicid inhibits the renal tubular secretion of several drugs, including penicillins, cephalosporins, NSAIDs, methotrexate, and even other medications we didn't just list.

03:20 So because of this factor, this can lead to increased blood levels and potential toxicity of these medications we just listed.

03:28 Now infusion reactions are common with Pegloticase.

03:31 More serious effects are things like anaphylaxis and the development of antibodies which can lead to loss of efficacy or effectiveness of the drug.

03:39 Remember it's also contraindicated in G6PD deficient patients because of the risk for hemolysis.

03:46 Colchicine is primarily used for acute gout and prophylaxis.

03:49 But colchicine deserves a mention here.

03:51 Now the common side effects are diarrhea, nausea, vomiting, and abdominal pain.

03:56 Sounds like fun, doesn't it? But there's more severe adverse effects.

04:00 Things like bone marrow suppression, myopathy, rhabdomyolysis, neurotoxicity, and significant drug interactions, particularly with CYP3A4 inhibitors.

04:11 Now the FDA has black box warnings and absolute contraindications for allopurinol.

04:17 Remember the key contraindication is going to be the HLA-B5801 positive patients of Asian or African descent because they have a markedly increased risk of those SCAR reactions.

04:28 It's also contraindicated in patients who have previously experienced severe hypersensitivity reactions to the drug.

04:35 Just a gentle reminder, Febuxostat carries a black box warning regarding increased risk of cardiovascular death and all-cause mortality compared to allopurinol.

04:45 Remember it's contraindicated in patients with known ischemic heart disease or heart failure.

04:50 Pegloticase is contraindicated in G6PD deficiency because there's an increased risk of hemolysis and it's contraindicated in patients who have experienced previous severe hypersensitivity reactions.

05:03 Colchicine has several important contraindications.

05:06 Now this drug is contraindicated in patients who have severe renal or hepatic impairment who are taking P-glycoprotein or CYP3A4 inhibitors, and in patients taking strong CYP3A4 inhibitors if they have renal or hepatic impairment.

05:23 Now the DRESS syndrome, that stands for drug reaction with eosinophilia and systemic symptoms, is a potentially life-threatening hypersensitivity reaction and this can occur with allopurinol and even with some of the other medications.

05:38 Now the signs and symptoms you want to be on the alert for and educate your patient about are any sign of a widespread rash with fever.

05:45 They might have facial swelling, lymphadenopathy, swollen lymph nodes, hepatitis, inflammation of their liver, eosinophilia, which is an elevated eosinophil count, or acute kidney injury.

05:58 Now the DRESS syndrome reaction typically begins about two to six weeks after starting the medication.

06:05 If you suspect the DRESS syndrome, the medication has to be stopped immediately and you'll need to start supportive care.

06:12 Now the mortality rate for someone with DRESS syndrome can be as high as 10%.

06:17 This is what underscores the importance of recognizing this reaction quickly and discontinuing the medication immediately.