Gout
Colchicine
Brand: Colcrys MOA: antiinflammatory-- inhibits microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis Warnings: GI symptoms, myopathy risk Side effects: diarrhea, nausea, myelosuppression, myopathy, neuropathy Dosing: --Attack treatment: 1.2 mg PO followed by 0.6 mg in 1 hour (do not exceed 1.8 mg in 1 hr or 2.4 mg in one day). If CrCl is <30, dose is the same, but do not repeat for two weeks. --Prophylaxis: 0.6 mg QD-BID If CrCl <30, decrease to 0.3 mg/day Notes: start within 36 h of symptom onset for attack treatment Wait 12 hours after treatment dose before resuming prophylaxis dosing
Allopurinol
Brand: Zyloprim MOA: xanthine oxidase inhibitors--> inhibit uric acid production Warnings: Hypersensitivity reactions, severe rash/SJS TEN, HLAB5801 testing prior to use especially in Asian populations, hepatotoxicity Side effects: rash, acute gout attacks, nausea, diarrhea, LFT increases Notes: may precipitate gout flare, use with colchicine or NSAD for 3-6 months.
Febuxostat
Brand: uloric MOA: xanthine oxidase inhibitor--> inhibit uric acid production Warnings: increased risk of CV death compared to allopurinol, limited to those who cannot tolerate allopurinol or who found allopurinol ineffective Contraindications: do not use with didanosine, mercaptopurine, azathioprine or pegloticase (will increase levels) Side effects: Hepatotoxicity, increased thromboembolic events, SJS/TEN
NSAIDs for gout attack
Indomethacin: 50 mg PO TID until resolved Naproxen: 750 mg x 1 PO, then 250 Q8h until resolved Celecoxib: 800 mg x 1 PO then 400 mg x1 later in day, then 400 mg BID x 1 week Notes: avoid in renal disease. Increase CVD risk and bleeding risk
Pegloticase
MOA: converts uric acid to allantoin, which is excreted Boxed warning: anaphylactic reactions--monitor and premedicate with antihistamines and steroids Contraindications: G6PD deficiency Notes: do not combine with allopurinol, febuxostat or probenecid (increased risk of anaphylaxis)
Probenecid
MOA: uricosoric--inhibits reabsorption of uric acid in the kidneys Contraindications: aspirin therapy, blood dyscrasias, UA kidney stones, initiation in acute gout attack Warnigns Decreased efficacy with CrCl <30, do not use with G6PD deficiency Side effects: Hypersensitivity reactions, hemolytic anemia Notes: may be used to increase beta lactam levels by decreasing beta lactam excretion
Normal serum uric acid levels
Males: 3.5-7.2 mg/dL Females: 2-6.5 mg/dL
Xanthine oxidase inhibitor DDIs
--Allopurinol and Febuxostat may increase concentration of mercaptopurine, active metabolite of azathioprine, do not use either concomitantly --Allopurinol and febuxostat may increase didanosine levels --Antacids decrease allopurinol levels
Acute gout attack therapy
--Colchicine --Sytemic steroids --NSAIDs --Combos of colchicine and steroid OR NSAID used in severe attacks --If on urate lowering therapy (ULT) continue through the attack --topical ice may be applied to the joint
Risk factors for gout
--Male sex --obesity --alcohol (esp. beer) --HTN --CKD --Lead intoxication --Diet --Increasing age --Certain medications
Foods that can precipitate/exacerbate gout
--organ meats --high fructose corn syrup --sardines --shellfish --fruit juices --sugar --excessive salt --red meat
Probenecid drug interactions
1. probenecid decreases the renal clearance of other medications such asa salicylates and methotrexate 2. probenecid is sometimes used with beta lactams to increase the concentration of the antibiotic 3. probenecid decreases efficacy of loop diuretics, but increases risk of loop diuretic toxicity
