RJ is a 57 year old male with a past medical history of previous ischemic stroke, stage 3 chronic kidney disease, and 1 previous gout attack approximately 3 months ago.  He presented to the emergency department 3 days ago with pain, swelling, and erythema in his right ankle where he was treated for an acute gout flare. 

Labs/vitals:

Ht: 5’12”

Wt: 186 lbs

BP: 118/75 mmHg

HR: 91 bpm

Temp: 98.2 F

eGFR: 35 mL/min

G6PD: 1.1 (5.5 - 20.5 units/gram hemoglobin)

Serum urate: 8.1 mg/dL (4.0 mg/dL- 8.5 mg/dL)

Medications:

Aspirin 81mg by mouth once daily

Since this is his second gout attack in 1 year, RJ was referred to the pharmacotherapy clinic to start urate lowering therapy (ULT).  What is an important consideration to keep in mind when choosing RJ’s ULT?

A. Allopurinol should be started at no greater than 100 mg/day initially

B. Prophylactic therapy should be administered concomitantly with ULT indefinitely

C. Pegloticase would be an appropriate choice for ULT in this patient

D. Febuxostat should be avoided in this patient due to his past medical history

Answer with rationale:

Gout is a form of arthritis caused by elevated serum urate concentration leading to the formation of urate crystals in the joints.  High uric acid levels can be caused by overproduction or underexcretion.  Acute gout attacks are commonly monoarticular and most commonly affect the first metatarsophalangeal joint.  The ankles, heels, knees, wrists, fingers, and elbows can also be affected.  Presentation typically includes joint pain, erythema, and swelling.  Acute management can often be done with NSAIDs, corticosteroids, or colchicine.

Urate lowering therapy (ULT) is the mainstay approach for chronic gout management.  Indications for ULT include frequent gout flares (≥2 flares/year), presence of one or more tophi, radiographic damage attributable to gout, and first flare in a patient with a history of kidney stones. 

Answer A is incorrect.  In a patient without chronic kidney disease (CKD), this answer choice would have been correct.  However, since RJ has stage 3 CKD with an estimated GFR of 35 mL/min, the initial dose of allopurinol would be 50 mg/day.  This lower starting dose is chosen to lower the risk of developing a hypersensitivity reaction which is a known, rare side effect of allopurinol therapy and would require discontinuation. A patient with the HLA-B*5801 allele would also be at risk for this hypersensitivity reaction. 

Answer B is incorrect.  While it is true that the initiation of ULT indicates the need for prophylaxis, prophylactic therapy is only continued for 3-6 months, not indefinitely.  Prophylactic therapy is needed because the initiation of ULT has been associated with gout flares.

Answer C is incorrect.  Pegloticase is a pegylated recombinant uricase derived from pigs which converts uric acid to allantoin to reduce serum urate concentrations.  It is never used first line because of its risk for anaphylaxis and is administered intravenously.  It is reserved for severe or refractory disease. Additionally, since RJ is G6PD deficient, this agent would be contraindicated due to increased risk of acute hemolytic anemia and methemoglobinemia.

Answer D is correct.  Febuxostat has a boxed warning for increased risk of death in patients with cardiovascular disease.  Since RJ has a previous history of ischemic stroke, febuxostat would not be optimal. Febuxostat should only be used in patients who cannot tolerate or have subclinical responses to allopurinol. 

Brands/generics covered:

Zyloprim (allopurinol), Krystexxa (Pegloticase), Uloric (febuxostat), Aspirin (Many brand names)

Naplex content domains covered:

2.A.2

Domain 2 Medication Use Process- A. Prescriptions and Medication Order Interpretation 2. Indications, Usage, and Dosing Regimens

2.A.4

Domain 2 Medication Use Process- A. Prescriptions and Medication Order Interpretation 4. Prescription regulations (eg, boxed warnings, risk evaluation and mitigation strategies)

3.B

Domain 3 Person-Centered Assessment and Treatment Planning- B. Health histories, screenings, and assessments

3.C.1

Domain 3 Person-Centered Assessment and Treatment Planning- C. Patient Health Conditions, including special populations and medication-related factors 1. Signs, Symptoms, and Findings of Medical Conditions, Etiology of Diseases, or pathophysiology

3.C.2

Domain 3 Person-Centered Assessment and Treatment Planning- C. Patient Health Conditions, including special populations and medication-related factors 2. Appropriateness of therapy