Gout

Question 1

Colchicine

Answer 1

(Colcrys)
75-95% of patients respond if drug is started with 24-48 hours after onset of acute symptoms

MOA: ↓leukocyte motility, ↓phagocytosis in joints and lactic acid production, thereby reducing deposition of crystals — no effect on uric acid levels

SE: GI toxicity (N/V/D, abd. Pain)- dose-related
Myelosuppression- indicative of colchicine toxicity (Bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets.)

CYP3A4 clarithromycin and azithromycin interaction –> possible death

Dose: 1.2 mg PO initially, for acute gout pain, followed by one dose of 0.6 mg one hour later; total dose = 1.8 mg
Dose adjustments required if patient on CYP3A4 and P-glycoprotein inhibitors

*Dose decreased 50% in renal insufficiency (CLcr 10-50ml/min)

Prophylaxis Dose:
0.6mg PO once or twice daily

Question 2

Prednisone (when to use)

Answer 2

Corticosteroids reserved for resistant cases or if CI to NSAIDs and colchicine

Can administer Corticosteroids intra-articular injections

Prednisone if multiple joints affected

• 30-60mg PO for 3-5 days, taper slowly by 5mg decreases over 10-14 days
• Rebound attacks if not tapered*

Question 3

Hyperuricemia Prophylactic Therapy (when to consider)

Answer 3

Consider if:

• > 2-3 attacks per year
• 1st attack severe or complicated
• Serum uric acid >10mg/dL (target 1000mg

Treatment options:
Allopurinol (Xanthine Oxidase Inhibitor)
Colchicine
Probenecid (Uricosuric Drug)
Febuxostat (Xanthine Oxidase Inhibitor)

Should not be given during an acute attack! (except colchicine)

Question 4

Allopurinol

Answer 4

(Zyloprim, Aloprim)
MOA: Xanthine Oxidase Inhibitor —> Decreases synthesis of uric acid (dose dependent)

Dose: 100mg PO daily (also dose for CrCl skin rash, leukopenia, GI, HA, urticaria
Severe –> severe rash, hepatitis, interstitial nephritis, eosinophilia (“allopurinol hypersensitivity syndrome”)
More common with renal insufficiency
Safe to use in ↓CLcr but with reduced dose

Drug interactions- azathioprine, 6-MP

Question 5

Febuxostat

Answer 5

(Uloric) - Chronic management of hyperuricemia
MOA: Selective xanthine oxidase inhibitor –> Decreases synthesis of uric acid

Dose: 40mg PO daily
May be titrated up to 80mg after 2 weeks uric acid of

Question 6

Probenecid

Answer 6

(Probalan)
MOA: ↑ renal clearance of uric acid by inhibiting post-secretory renal proximal tubular reabsorption

Dosing: 250mg PO bid x 1-2weeks, 500mg PO bid x 2weeks, then daily dose ↑ by 500mg every 1-2 weeks until controlled (max 2g/d)

ADEs: GI irritation, rash and hypersensitivity

***CI in patients with CLcr

Question 7

Pegloticase

Answer 7

(Krystexxa) — only for Treatment Failure Gout (SEVERE)
MOA: Pegylated urate oxidase —> converts uric acid to allantoin

Dosing: 8mg IV over 2 hours q 2 weeks

MUST pre-medicate: Oral anti-histamine, APAP and IV corticosteroid

CI: G6PD Deficiency
W/P: Anaphylaxis, infusion rxns, flares, CHF
ADR: gout flares, infusion rxns, nausea, ecchymosis (bruising)

D/C therapy immediately if SUA starts to rise

Question 8

Lesinurad

Answer 8

(Zurampic)

Indicated in combination with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone

MOA: Uric acid reabsorption inhibitor (SURI) –> Increases renal excretion of uric acid

Dose: 200 mg PO daily (with food and water)
Not recommended for CrCl