GOUT 2025

GOUT G. Morataya, PharmD Assistant Professor West Coast University 1 OBJECTIVES ¡ Discuss the pathophysiology of gout ¡ Review acute gout attacks ¡ Explore chronic hyperuricemia ¡ Examine urate lowering therapy (ULT) ¡ Address lifestyle modifications to help manage uric acid levels ¡ Tackle on asymptomatic hyperuricemia 2 Gout • Gout encompasses a group of dx • Monosodium urate (MSU) crystals in synovial fluid and lining • MSU crystals (tophi) in soft tissue surrounding joints • Recurrent attacks of gouty arthritis • Urolithiasis • Interstitial renal dx 3 of process urination Skip 4 skip 5 goutond hyperoreoomiaarevalfdiffent HYPERURICEMIA Puricacid ¡ Serum supersaturated w/MSU crystals ¡ > 7mg /dL exceed solubility at 37 C (98.6 F) ¡ Hyperuricemia is often asymptomatic ¡ Not synonymous or interchangeable with term gout ¡ Gout often associated w/hyperuricemia § However elevated SUA is not a prerequisite for gout attacks 6 CONDITIONS ASSOCIATED WITH HYPERURICEMIA § § § § § § § § § § § § Obesity Diabetic ketoacidosis Sarcoidosis Myeloproliferative and Lymphoproliferative disorders Congestive heart failure Lactic acidosis Renal dysfunctionso Down syndrome Starvation Lead toxicity Chronic hemolytic anemia Hyperparathyroidism Notfitting yin Toxemia of pregnancy Acute alcoholism Pernicious anemia Hypoparathyroidism Psoriasis Hypothyroidism Hypoxanthine-guanine phosphoribosyl-transferase deficiency § Phosphoribosylpyrophosphate synthetase overactivity § Polycythemia veraBerylliosis § Renal transplantation § § § § § § § 7 Etiology of Gout 1. Dx secondary to deposition of 3. MSU crystals § Deposits w/in synovial fluid and lining around the joints 2. Underexcretion § Impaired renal clearance of UA is main cause of gout and hyperuricemia § Many other factors may impair clearance of UA: § Excess EtOH, CHD, HTN, metabolic syndrome Overproduction § Excessive intake of dietary purines from meat, seafood, dried peas and beans, EtOH § Neoplastic dx § TLS from aggressive cytotoxic chemotherapy 8 PATHOPHYSIOLOGY ¡ UA serves no biological fxn; it is the end product of purine metabolism ¡ Primarily excreted renally ¡ ­SUA can result from an ­in production or ¯renal excretion ¡ MSU crystals form and deposit into soft tissues forming hard nodules called tophi ¡ Tumor lysis syndrom (TLS): complication of aggressive chemotherapy § When cells are lysed open, purines are released into the blood and quickly converted to uric acid § Can à acute gout and electrolyte abnormalities 9 PATHOPHYSIOLOGY liverhave lab home But No sump ¡ UA is excreted 2/3 renally and 1/3 in GI tract under normal conditions ¡ Pts may remain asymptomatic w/­SUA (many pts do not present w/gout) ¡ MSU can crystallize in the joints à severe, painful gout attacks ¡ Commonly presents after many years of hyperuricemia 10 RISK FACTORS ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ Male gender Obesity Biggestone Excessive EtOH consumption (particularly beer) HTN CKD Lead intoxication Advanced age Medications that increase UA w lotsofpurines 11 MEDICATIONS THAT INCREASE UA ¡ Aspirin (higher doses)t 325 ¡ Cyclosporine and Tacrolimus Igivenfor transplants I ¡ Cytotoxic chemotherapy ¡ Diuretics ¡ Levodopa ¡ Niacin sinanet I'm ¡ Ribavirin and interferon HEP E 12 Clinical Presentation ¡ Typically diagnosed by symptoms as opposed to synovial fluid aspirate ¡ Joint pain in lower or upper extremities ¡ Urolithiasis ¡ Tophi deposits in: § § § § Cartilage Tendons Membranes Soft tissue 13 Clinical Presentation ¡ S/Sx § § § § Fever Pain Erythema Swelling and joint inflammation ¡ Laboratory values § ­SUA § NL: 2 – 7.2 mg/dL § Leukocytosis ¡ Other tests § MUA crystals in synovial fluid § Radiography indicated asymmetric soft tissue swelling overlying involved joint § Subcortical cysts w/o erosions 14 Clinical Manifestations ¡ Acute gout § Monoarticular arthritis ¡ Podagra § The 1 st metatarsophalangeal joint is the most commonly affected joint, and the term podagra specifically refers to gout in this joint. ¡ Atypical gout: § Polyarthritic affected joints (RA similarly presents) 15 in D G and incesion arrest 16 MANAGEMENT OF GOUT ¡ Establish Diagnosis ¡ Baseline Recommendations § Patient Education toBeget § Diet § Lifestyle ¡ Consider secondary causes § § § § § § § § § Obesity Alcohol Hypertension DM metabolic syndrome Hyperlipidemia History of stones Renal disease Genetics Medications 18 TREATMENT GOALS ¡ Improve s/sx ¡ Urate level < 6mg/dL (ULT) ¡ Prevent reoccurrences 19 knowyour ACUTE GOUT ATTACK TX ¡ Colchicine (Colcrys®) § MoA: Inhibits reabsorption of UA in kidneys, which ­UA excretion § CIs: dosing Knowdiffeut der type of § Concomitant use of a P-gp or strong CYP 3A4 inhibitor in presence of renal or hepatic impairment § Renal impairment § Hepatic impairment § Warnings: § GI sxs, N/V, neuromuscular toxicity, concomitant use of cyclosporine, diltiazem, verapamil, fibrates, and statins (­myopathy risk) § Side effects: § § § § § § Diarrhea N/V ¯vitamin B Myelosuppresion Myopathy Neuropathy § Dosing § Tx: 1.2mg orally followed by 0.6mg in 1 hour (1.8mg /hr or MDD 2.4mg) § Do not repeat dose before 3 days HII § CrCl < 30mL/min, do not repeat initial dose prior to 2 weeks § Prx: 0.6mg once or twice daily § CrCl < 30mL/min, ¯ to 0.3mg /day 20 want anhour ACUTE GOUT ATTACK TX ¡ NSAIDS § Naproxen (i.e. Naprosyn®) DON't needtoknow Thedosing § 750mg by mouth once, then ¯to 250mg every 8 hours until gout attack resolved § Indomethacin (Indocin®) § 50mg by mouth three times daily until gout attack resolved § Sulindac (Clinoril®) § 200mg by mouth twice daily until gout attack resolved § Celecoxib (Celebrex®) § 800mg by mouth once, followed by 400mg by mouth on day one; then twice daily for one week § Avoid use in severe renal dx § CVD risk 21 ACUTE GOUT ATTACK TX ¡ Steroids: needtoknow whatneedsto beusedfor Regimen 1: 0.5mg/kg/day by mouth for 5 – 10 days (no taper required) Acutegab Regimen 2: 0.5 mg/kg/day 2 – 5 days, then taper (¯by 5mg daily) over 7 – 10 § PredniSONE/PredniSOLONE § § days § MethylPREDNISolone (Medrel, Solu-Medrol) attack § IA if 1 –2 large joints involved § Oral: Methylprednisolone dose pack § Traimcinolone § IM: Triamcinolone 60mg once, then begin oral prednisone ¡ AE § Acute sxs: Hyperglycemia, insomnia, HTN, ­appetite, edema, nervousness § Mild pain at injection site § Repeated injections can ­risk of joint damage 22 ACUTE GOUT ATTACK TX ¡ Parenteral Corticosteroid: § Corticotropin § 25 – 40 units given SubQ; with repeat doses as clinically indicated § Indication: § Acute gout treatment (off-label use) ¡ Place in therapy for: § NPO pts § Pts w/hx of CHF, chronic renal insufficiency, GI bleed, and intolerant/failed NSAID and colchicine ¡ Considerations § Difficult to obtain § Expensive § Excellent for pts w/CI comorbidities 23 XANTHINE OXIDASE INHIBITORS ¡ Allopurinol (Zyloprim®) § MoA: Inhibits XO à ¯UA production thereby ¯SUA levels § Warnings: § Hypersensitivity rxn can occur; severe rash (SJS/TEN) § ­risk in renal impairment § Side effects: § Rash, acute gout attacks, nausea, diarrhea, ­LFTs § Dosing § Start at 100mg daily § Titrate slowly up until SUA < 6 mg/dL § Divide doses > 300mg § Use either NSAIDS or colchicine 0.6 mg once or twice daily concurrently for the first 3 – 6 months due to high incidence of gout attacks w/initiation of ULT 24 XANTHINE OXIDASE INHIBITORS ¡ Febuxostat (Uloric®) § MoA: Inhibits XO à ¯uric acid production thereby ¯SUA levels § CIs § Concomitant use w/didanosine, mercaptopurine, and pegloticase § Warnings: § Hepatotoxicity § Possible ­ in thromboembolic events § Administer concurrently with NSAID os colchicine up to 6 months to prevent gout flare § Side effects: § Rash, nausea, arthralgia § Dosing § Start at 40mg daily § Titrate up to 80 mg if SUA not < 6 mg/dL after 6 weeks 25 TRANSPORTER PROTEIN INHIBITOR ¡ Lesinurad (Zurampic®) § MoA: Inhibits transporter proteins involved in uric acid reabsorption à ¯SUA levels § Warnings: § CI in severe renal impairment, ESRD, HD, Kidney tx recipients § TLS § Side effects: § HA, GI reflux dx, infection (influenza) § Dosing § Start at 200mg daily § In combination with colchicine or Uloric® 26 URICOSURIC ¡ Probenecid § MoA: Inhibits reabsorption of UA in kidneys, which ­UA excretion § Warnings § ¯effectivity with CrCl <30mL/min § ­risk of hemolytic anemia in G6DP deficient pts § CIs: § § § § § Concomitant aspirin therapy Blood dycrasias Nephrolithiasis Children < 2yo Initiation in gout attack § Side effects: § Hypersensitivity rxn, hemolytic anemia § Dosing § Start at 250mg twice daily § Can ­up to 2g/day § ­dosage in increments of 500mg every 4 weeks 27 URATE-OXIDASE ENZYME ¡ Pegloticase (Krystexxa®) § MoA: Form of uricase, an enzyme which converts UA to allantoin (­solubility); it does not block UA formation § BBW § Anaphylactic rxns § Pre-medicate w/antihistamines and corticosteroids (highest risk w/SUA > 6mg/dL) § ­risk of hemolytic anemia in G6DP deficient pts § CIs: § G6DP deficiency § Side effects: § § § § Antibody formation Gout flare Infusion rxn Nausea, bruising, erythema § Dosing § 8mg IV every two weeks § Monitoring § SUA, infusion rxn, anaphylaxis 28 URATE-OXIDASE ENZYME ¡ Rasburicase (Elitek®) noton The Eton § MoA: Form of uricase, an enzyme which converts UA to allantoin; it does not block UA formation § BBW § § § § Anaphylaxis Hemolysis Methemoglobinemia Interference w/SUA measurements § CIs: § G6DP deficiency § Hypersensitivity § Side effects: § § § § § Peripheral edema HA Anxiety Rash, N/V, abdominal pain, diarrhea or constipation ­ALT, hyperbilirubinemia, sepsis, hypophosphatemia, § Dosing § 8mg IV every two weeks § Monitoring § SUA, CBC 29 ALTERNATE THERAPY ¡ IL-I Inhibitor § Canakinumab § Anakinra justknow exist The 30 URATE-LOWERING THERAPY ¡ULT § ULT should only be initiated w/one of the following: § Pts w/gout w/frequent attacks (≥2/yr) § In the presence of urate tophi § In the presence urate nephropathy (nephrolithiasis, urolithiasis) § Do not begin long-term ULT prior to gout attack resolution § 2 weeks 31 PRX At ONTREXAM ¡ ULT Prx § § § § o 31doing Prx: 0.6mg once or twice daily (up to 6 months) CrCl < 30mL/min, ¯ to 0.3mg/day region NSAIDS (limit to 6 weeks) If acute attack occurs while on allopurinol, do not stop tx; adjust colchicine, NSAIDs, or corticosteroids appropriately. ME ¡ TLS § For high-risk pts receiving certain types of chemotherapy § High-dose allopurinol § Alternative: Rasburicase § If TLS occurs tx to ¯ SUA, and correct electrolyte levels § Tx: High-dose allopurinol 32 ASYMPTOMATIC HYPERURICEMIA ¡ Do NOT tx § For high-risk pts receiving certain types of chemotherapy § High-dose allopurinol § Alternative: Rasburicase § If TLS occurs tx to ¯ SUA, and correct electrolyte levels § Tx: High-dose allopurinol 33 MONITORING AN FOLLOW UP ¡ SUA levels ¡ Renal Fxn § SCr § BUN ¡ Electrolytes ¡ Resolution of s/sx 34 NONPHARMACOLOGIC THERAPY ¡ Ice § Shown to reduce pain in gout attacks in conjunction w/colchicine or oral steroids ¡ ¯EtOH consumption § Beer (­purine content) ¡ Diet o § Cautious of meat and seafood intake § Food beneficial in preventing ­SUA § Yogurt § Milk § Low-fat dairy products/proteins ¡ Lifestyle modifications § Weight loss § Exercise 35 CLINICAL PEARL ¡ When gout associates w/diuretic therapy, stop the diuretic if possible; for HTN and hyperlipidemia consider use of losartan and fenofibrate, respectively (both have modest uricosuric ef fects) 36 Review ¡ JT is a 66 yo male ¡ CC: “My right foot is killing me, it hurts so bad,…I never felt anything like this before.” ¡ PMH: Hyperlipidemia, HTN, otherwise healthy ¡ Current Meds: § Atorvastatin 40 mg once daily by mouth § Furosemide 40 mg twice daily by mouth § Gemfibrozil 600 mg twice daily by mouth (30 minutes before meal) ¡ OTC/Supplements § Fish oil 2000mg twice daily 37 Review ¡ Subjective findings § Podagra § Pain 9/10 at affected area (1 st metatarsophalangeal joint) § Tender to touch ¡ Objective Findings § SUA: 10 mg/dL § BP: 145/88 § Lipid panel 138 4.5 100 25 20 0.9 90 § LDL: 165 § HDL: 45 § Triglycerides: 140 38 Review ¡ What is the prx dosing recommended for ULT for colchicine? A. B. C. D. E. 0.6mg once or twice 0.6mg once or twice 0.3mg once or twice 0.6mg once or twice None of the above daily daily daily daily (up to 6 months) (limit to 6 weeks) (up to 6 months) (up to 12 months) renal Apthavegoodfunction need of 39 Review ¡ When appropriate, ULT should be started how long after an acute gout attack? A. B. C. D. E. 1 2 3 4 6 week weeks weeks weeks weeks 40