NAPLEX Question of the Week: Oh no, my big toe!

Gout is the subject of our question of the week! May the 4th be with you as you prepare for the exam.
NAPLEX Question of the Week: Oh no, my big toe!

RJ is a 63-year-old African American male who presents to your pharmacotherapy clinic with erythema, swelling, and pain of the right metatarsophalangeal joint. The patient explains that his symptoms began yesterday and that he’s experienced 3 similar episodes in the past year, for which he has managed with topical ice. Today, he describes his pain as a 6/10 and states that the cold packs have not relieved his pain. The patient’s PMH is significant for diabetes, hyperlipidemia, and MI 9 months ago. Current medications include Zestril 20mg daily, Toprol XL 25mg daily, Glucophage 500mg BID, Lipitor 40mg daily, Plavix 75mg daily, and aspirin 81mg daily. The patient drinks 3 beers a day and denies smoking. The PCP diagnoses the patient with an acute gout attack. The provider decides to prescribe Colcrys to manage the patient’s gout attack and asks you for a recommendation for the chronic management of gout. 

Pertinent Labs: 

  • Uric acid level: 9.1mg/dL (Hyperuricemia: serum urate >7 mg/dL for men; >6 mg/dL for women) 
  • Scr: 0.9 (0.7 – 1.3 mg/dL) 
  • Crcl: 98ml/min 
  • HLA-B *5801: positive, heterozygous  
  • CBC – unremarkable  

Vitals:  

  • BP: 125/78, RR: 16, HR: 80 bpm 
  • Weight – 85kg     Height – 68 inches  

Which of the following would be appropriate options to initiate in this patient for urate-lowering therapy?  

A. Zyloprim 300mg PO daily  

B. Probenecid 250mg PO BID x 1 week followed by 500mg PO BID 

C. Uloric 40mg PO daily  

D. Probenecid 500mg PO TID x 1 week followed by 250mg PO BID 

E. Zyloprim 100mg PO daily  

 

Answer with rationale: B 

Brand/Generics covered: Zyloprim (allopurinol), Uloric (febuxostat), Colcrys (colchicine), Glucophage (metformin), Lipitor (atorvastatin), Zestril (lisinopril), Plavix (clopidogrel), Toprol XL (metoprolol succinate)

Explanation: 

Gout is characterized by painful, joint inflammation, most commonly in the first metatarsophalangeal joint resulting from high levels of uric acid or hyperuricemia. High levels of uric acid can be from the body’s overproduction of uric acid or underexcretion of uric acid. In chronic gout, patients may develop deposits of uric acid crystals called tophi, which usually form around joints. Acute gout attacks are treated with agents such as colchicine, NSAIDs, and glucocorticoids while chronic gout is treated with urate-lowering agents (xanthine oxidase inhibitors and uricosuric agents). 

According to the 2020 American College of Rheumatology Guidelines (ACR), RJ qualifies for pharmacologic urate-lowering therapy because he has frequent gout flares, with frequent being defined as 2 annually. Other indications for pharmacology ULT include >1 subcutaneous tophi or evidence of radiographic damage attributable to gout. Urate lowering therapy includes xanthine oxidase inhibitors (allopurinol, febuxostat) and uricosuric agents (probenecid and pegloticase). Zyloprim (allopurinol) is considered first-line therapy and is strongly recommended over all other urate-lowering therapy.  However, the use of allopurinol is inappropriate in this patient due to the presence of the HLA-B*5801 allele.  The presence of the HLA-B*5801 allele is strongly associated with allopurinol-induced severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). Therefore, options A and E would be inappropriate for this patient. Additionally, option E is incorrect as the initial dose of allopurinol in the treatment of gout should not exceed 100mg daily.  Per 2020 ACR guidelines, testing for the HLA-B*5801 allele prior to starting allopurinol is conditionally recommended for patients of Southeast Asian descent (e.g., Han Chinese, Korean, Thai) and for African American patients, over not testing for the HLA-B*5801 allele. Probenecid is considered an alternative first-line agent and should be considered in those who do not respond to or cannot tolerate allopurinol. ACR guidelines recommend starting probenecid at a low dose (500mg once or twice daily) with dose titration over starting at a higher dose. Therefore, option B is appropriate to begin in this patient, and option C is incorrect. Uloric (febuxostat) has a boxed warning on its label because it has been shown to increase the risk of death in those patients with cardiovascular disease. RJ has established cardiovascular disease with a recent MI and therefore option C would be inappropriate.  

It is very important to note that there are several medications that are known to increase serum urate levels including but not limited to thiazide diuretics, niacin, cyclosporine, and low dose aspirin.  RJ is currently taking aspirin which could be contributing to his high uric acid level. Alcohol can also precipitate gout attacks and assessing the patient’s willingness to limit their alcohol intake should be discussed.

Remember that once patients begin ULT, the target serum uric acid level is <6mg/dL and uric acid levels should be measured every 2-5 weeks during titration and every 6 months once at goal.   

NAPLEX Exam Competencies Covered: Area 2 (Identify Drug Characteristics), 2.2 Commercial availability; prescription or non-prescription status; brand, generic, or biosimilar names; physical descriptions; or how supplied; Area 3 (Develop or Manage Treatment Plans), drug dosing or dosing adjustments; duration of therapy; 3.6 drug contraindications, allergies, or precautions. 

References  

ACR Guidelines  

Allopurinol Package Insert 

Febuxostat Package Insert 

Appreciate the wonderful hospitality of VCU, MUSC, and UGA students, staff, and faculty as our team completed live reviews this past week. You are almost there friends so keep up the studying!

Dr. B