Gout

Question 1

Gout/Hyperuricemia

Answer 1

Allopurinol (Zyloprim)
Colchicine (Colcrys)
Febuxostat (Uloric)
Probenecid (Benemid)
Rasburicase (Elitek)
Pegloticase (Krystexxa)

Question 2

Xanthine Oxidase Inhibitors

- For chronic gout

Answer 2

• Allopurinol (Zyloprim)
• Probenecid (Benemid)
• Fobuxostat (Uloric)

Question 3

Allopurinol (Zyloprim)

• Primary or secondary gout (Chronic treatment)
• Chemo pts at risk of tumor lysis syndrome (hematologic malignancies)
• Hyperuricemia in pts with recurrent calcium oxalate stones
• NOT for asymptomatic hyperuricemia

Answer 3

• MOA: Xanthine oxidase inhibitor, purine analog, reduces production of uric acid
• ADR: RASH ( can lead to SJS, d/c allopurinol w/ first sign of rash); D/N; increased LFTs; Acute gout attack (administer colchicine or NSAID upon initiation of allopurinol, w/draw once uric acid level decreased)
• DRUG INTERACTIONS: Azathioprine, 6-mercaptopurine (inhibits enzymatic inactivation, reduces dose of AZA or 6-MP); warfarin; theophyline (may increase levels)
• Aids in dissolution of tophi
• Prevents development or progression of chronic gout (keeps uric acid level below solubility limit)
• Decrease risk of permanent renal damage
• Start low, go slow (until uric acid level

Question 4

Probenecid (Benemid)

• Indicated for hyperuricemia associated with gout (chronic treatment)
• Adjuvant to PCN or ampicillin (to increase levels)

Answer 4

• MOA: Blocks renal tubular reabsorption of urate (increases uric acid excretion, decreases serum urate levels)
• Also inhibits PCN secretion (increases PCN levels)
• ADR: HA, N, worsening of gout flare, dizziness, uric acid kidney stones, blood dyscrasias

Question 5

Fobuxostat (Uloric)

- Gout chronic treatment

Answer 5

• Xanthine oxidase inhibitor
• Higher rate of CV events than with allopurinol
• Hepatic failure reported (measure LFTs at baseline and monitor during treatment)
• NO RENAL adjust

Question 6

Lesinurad (Zurampic)

- Indicated for use with a XOI when target uric levels not achieved (NOT for monotherapy)

Answer 6

• MOA: blocks uric acid reabsorption
• ADR: Increased sCr, renal failure, kidney stones; HA, flu, GERD
• DRUG INTERACTIONS: metabolized by CYP 2C9, weak induce of 3A4 (may reduce efficacy of amlodipine, sildenafil)

Question 7

Uric acid lowering agents

Answer 7

• Colchicine (Colcrys)

- Pegloticase (Krystexxa)

Question 8

Colchicine (Colcrys)

• Prophylaxis and treatment of ACUTE gout flares
• Familial mediterranean fever

Answer 8

• MOA not well known (inhibits microtubule formation in bone cells and prevents neutrophil activation)
• Narrow therapeutic window
• ADR: DIARRHEA!!!!!!; Throat pain
• WARNING: blood dyscrasias, neuromuscular toxicity and rhabdomyolysis (increased risk in elderly and renal insufficiency); PGP (cyclosporine, ranolazine) and CYP 3A4 substrate (contraindicated with strong 3A4 inhibitors– ketoconazole, ritonavir, clarithromycin)
• RENAL adjust

Question 9

Pegloticase (Krystexxa)

- For refractory chronic gout

Answer 9

• PEGylated uricase enzyme
• Catalyzes oxidation of uric acid to allantoin
• COMMON ADR: gout flare, infusion rxn, N/V/C, ecchymosis, nasopharyngitis, chest pain, CHF exacerbation
• Given IV (risk of anaphylaxis and infusion rxn– MUST be given in infusion center, requires premed w/ antihistamines– benedryl and corticosteroids)

Question 10

Rasburicase (Elitek)

- For hyperuricemia due to tumor lysis syndrome

Answer 10

• Recombinant urate-oxidase
• Catalyzes enzyme oxidation of uric acid into allantoin
• ADR: anaphylaxis, hemolysis, methemoglobinemia

Question 11

Acute Gout guideline

Answer 11

• Acute gouty arthritis attacks should be treated w/ pharmacologic therapy
• To provide optimal care, treatment should be initiated w/in 24 hrs of acute gout attack onset
• Ongoing ULT should NOT be interrupted during an acute gout attack
• NSAIDs (or COX-2 inhibitor); systemic corticosteroids; colchicine

Question 12

Prophylaxis

Answer 12

• With or just prior to initiating ULT (urate lowering therapy)
• First line: low dose colchicine OR low dose NSAIDs
• Second line: low dose prednisone/prednisolone

Question 13

Hyperuricemia/Chronic Gout

Answer 13

• Pt education: diet, lifestyle, treatment objectives, management of comorbid conditions
• First line pharmacologic ULT in gout: XOI therapy (allopurinol or febuxostat)
• Target serum urate level