A Bout with Gout. ACCREDITATION Pharmacy

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A Bout with Gout ACTIVITY DESCRIPTION Over the past two decades, the prevalence of gout has increased dramatically. Today, gout affects an estimated 4% of the U.S. population or around 8.3 million people. Properly treated, gout rarely poses a long-term health threat; left untreated, however, gout can develop into a painful and disabling chronic disorder. Non-adherence among gout patients remains an ongoing problem, with over half of the respondents in a recent survey labeled as such. This same study revealed that patients with more active gout - the very group who should be receiving drug therapy - are undertreated. Due to the availability of non-prescription medications, community pharmacists may be the first health care contact a gout sufferer reaches out to for help. This program will review the epidemiology, pathogenesis, diagnosis, and treatment strategies for the pharmacist involved in the management of the patient with gout, as well as increase the understanding that gout should be managed as a chronic and progressive disease in the same light as other more prevalent disease states. TARGET AUDIENCE The target audience for this activity is pharmacists, pharmacy technicians, and nurses in hospital, community, and retail pharmacy settings. LEARNING OBJECTIVES After completing this activity, the pharmacist will be able to: Identify the general clinical presentations of gout, differentiating between acute attacks and chronic underlying disease. Describe the current and emerging pharmacological approaches to the management of gout (pharmacologic profiles, efficacy, side effects, & adverse events). Employ counseling techniques with a special focus on benefits of drug therapy compliance, drug interactions, and advise when a physician visit is necessary. After completing this activity, the pharmacy technicians will be able to: List symptoms of gout List different treatment strategies for gout ACCREDITATION Pharmacy PharmCon, Inc. is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Nursing PharmCon, Inc. is approved by the California Board of Registered Nursing (Provider Number CEP 13649) and the Florida Board of Nursing (Provider Number 50-3515). Activities approved by the CA BRN and the FL BN are accepted by most State Boards of Nursing. CE hours provided by PharmCon, Inc. meet the ANCC criteria for formally approved continuing education hours. The ACPE is listed by the AANP as an acceptable, accredited continuing education organization for applicants seeking renewal through continuing education credit. For additional information, please visit: http://www.nursecredentialing.org/renewalrequirements.aspx Universal Activity No.: 0798-0000-16-010-L01-P Credits: 1.0 contact hour (0.1 CEU) Release Date: 04/15/2016 freece Expiration Date: 4/15/2017 ACPE Expiration Date: 4/15/2019 ACTIVITY TYPE Knowledge-Based Live Webinar FINANCIAL SUPPORT BY AstraZeneca

Maria Thurston, PharmD, BCPS Clinical Assistant Professor, Mercer University College of Pharmacy ABOUT THE AUTHOR Dr. Maria Thurston graduated with honors from the University of Georgia College of Pharmacy. She completed a PGY-1 pharmacy practice residency with the Atlanta Veterans Affairs Medical Center in Decatur, Georgia and a PGY-2 Ambulatory Care residency specializing in academia with the University of Georgia/Charlie Norwood Veterans Affairs Medical Center, where she also obtained a Graduate Certificate in Clinical Pharmacy. Dr. Thurston s areas of interest and expertise include: cardiovascular risk reduction, health coaching, patient education, interprofessional education and professional development. Dr. Thurston achieved the designation of Board Certified Pharmacotherapy Specialist in 2011. She was named the Georgia Society of Health-System Pharmacists Outstanding Young Health-System Pharmacist in 2012. She is currently serving as a Clinical Assistant Professor in the Department of Pharmacy Practice with Mercer University College of Pharmacy where she coordinates the Nervous Systems Disorders II course and teaches various didactic lectures. She actively practices in a collaborative outpatient internal medicine clinic at Atlanta Medical Center s Sheffield HealthCare Center, where she precepts both pharmacy students and residents. She serves on committees for multiple regional and national pharmacy organizations and is a peer reviewer for scholarly journals. Her regional and peerreviewed publications are focused on topics relevant to primary care practice, and she has research and grants in the areas of medication adherence, health literacy, diabetes, heart failure, interprofessional education, and professional development. FACULTY DISCLOSURE It is the policy of PharmCon, Inc. to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer of any commercial product(s) and/or service(s) discussed in an educational activity. Maria Thurston reports no actual or potential conflict of interest in relation to this activity. Peer review of the material in this CE activity was conducted to assess and resolve potential conflict of interest. Reviewers unanimously found that the activity is fair balanced and lacks commercial bias. Please Note: PharmCon, Inc. does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced and objective. Occasionally, faculty may express opinions that represent their own viewpoint. Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not intended as a substitute for the participant s own research, or for the participant s own professional judgement or advice for a specific problem or situation. Conclusions drawn by participants should be derived from objective analysis of scientific data presented from this activity and other unrelated sources. Neither freece/pharmcon nor any content provider intends to or should be considered to be rendering medical, pharmaceutical, or other professional advice. While freece/pharmcon and its content providers have exercised care in providing information, no guarantee of it s accuracy, timeliness or applicability can be or is made. You assume all risks and responsibilities with respect to any decisions or advice made or given as a result of the use of the content of this activity.

A Bout With Gout 4/12/2016 1 Faculty: Maria Miller Thurston, Pharm.D., BCPS A Bout With Gout Activity ACCREDITATION Universal Activity Number 0798-0000-16-008-H01-P Credits 1.0 contact hour(s) Activity INSTRUCTION Faculty Maria Thurston, PharmD, BCPS Clinical Assistant Professor, Mercer University College of Pharmacy Faculty Disclosure Maria Thurston has no actual or potential conflicts of interest in relation to this activity. Learning OBJECTIVES Identify the general clinical presentations of gout, differentiating between acute attacks and chronic underlying disease. Describe the pharmacology and clinical role of clozapine. Employ counseling techniques with a special focus on benefits of drug therapy compliance, drug interactions, and advise when a physician visit is necessary. Legal DISCLAIMER The material presented here does not necessarily reflect the views of PharmCon, Inc. or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. 4/12/2016 2 1

Learning Objectives 1. Identify the general clinical presentations of gout, differentiating between acute attacks and chronic underlying disease 2. Describe the current and emerging pharmacological approaches to the management of gout (pharmacologic profiles, efficacy, side effects, & adverse events). 3. Employ counseling techniques with a special focus on benefits of drug therapy compliance, drug interactions, and advise when a physician visit is necessary. 4/12/2016 3 Gout Type of inflammatory arthritis Resulting from uric acid crystal deposition into joint spaces Associated with hyperuricemia (serum uric acid [SUA] above 6.8 mg/dl) Leads to an inflammatory reaction Acute attacks & chronic underlying disease ~8.3 million patients affected (3.9% of adults) in US Incidence rising, in part due to increase in other risk factors 4/12/2016 4 Neogi T. N Engl J Med 2011;364:443 52. Zhu Y, Pandya BJ, Choi HK. Arthritis Rheum. 2011;63(10):3136 3141. 2

Risk Factors Male gender Obesity, hypertension, dyslipidemia, and the metabolic syndrome Type 2 diabetes mellitus, chronic kidney disease (CKD), and coronary artery disease (but no causal relationship) Drug therapy Thiazide and loop diuretics, niacin, pyrazinamide, calcineurin inhibitors, and occasionally aspirin (81 mg daily okay) Stress, trauma, alcohol ingestion, infection, surgery, and rapid lowering of SUA with urate lowering therapy (ULT) 4/12/2016 5 Khanna D, Fitzgerald JD, Khanna PP, et al. Arthritis Care Res. 2012;64(10):1431 1446. Roddy E, Choi HK. Rheum Dis Clin North Am. 2014;40(2):155 175. Diagnosis Presumptive diagnosis Based on presenting symptoms Confirmed later with laboratory and other diagnostic tests Severe joint pain, swelling, tenderness, and erythema Rapidly peak Elevated SUA level, mildly elevated WBC, increased ESR Definitive diagnosis Aspiration of joint fluid or tophus monosodium urate (MSU) crystals 4/12/2016 6 Zhang W, Doherty M, Pascual E, et al. Ann Rheum Dis. 2006;65(10):1301 1311. 3

Clinical Presentation Acute attack Severe pain, swelling, redness, and warmth in affected joint(s) Usually monoarticular: metatarsophalangeal joint, podagra most common Mild fever may be present Maximal symptom intensity within 6-12 hours Resolves in a few days to several weeks Chronic underlying disease Absence of acute symptoms, unless recurrent attack Chronic gouty arthritis Other complications Neogi T. N Engl J Med 2011;364:443 52. 4/12/2016 7 Complications Long-term consequences of gout and hyperuricemia Joint destruction Tophi Hands, wrists, elbows, or knees Take 10 or more years to develop Nephrolithiasis Nephropathy https://www.nlm.nih.gov/medlineplus/ency/imagepages/19833.htm 4/12/2016 8 Neogi T. N Engl J Med 2011;364:443 52. 4

Gout Management 4/12/2016 9 Clinical Practice Guidelines European League Against Rheumatism (EULAR) Published in 2006 by Zhang et al., 2 parts The British Society for Rheumatology (BSR) Published in 2007 by Jordan et al. American College of Rheumatology (ACR) Published in 2012 by Khanna et al., 2 parts 4/12/2016 10 Zhang W, Doherty M, Pascual E, et al. Ann Rheum Dis. 2006;65(10):1301 1311. Zhang W, Doherty M, Bardin T, et al. Ann Rheum Dis. 2006;65(10):1312 1324. Jordan KM, Cameron JS, Snaith M, et al. Rheumatol Oxf Engl. 2007;46(8):1372 1374. Khanna D, Fitzgerald JD, Khanna PP, et al. Arthritis Care Res. 2012;64(10):1431 1446. 5

Nonpharmacologic Therapy Acute attack management Adjunctive role Usually not effective when used alone Immobilization of the affected extremity Applying ice packs most effective Analgesic medications (acetaminophen or opioids) Prevention of acute attacks Lifestyle modification Weight loss, limit alcohol, hydration, manage co-morbidities, and improve nutrition 4/12/2016 11 Schlesinger N, Detry MA, Holland BK, et al. J Rheumatol. 2002;29(2):331 334. Pharmacologic Management Acute attack Nonsteroidal anti-inflammatory drugs (NSAIDs) Colchicine Corticosteroids Chronic underlying disease: Urate lowering therapy Xanthine Oxidase Inhibitors Allopurinol Febuxostat Uricosuric Probenecid Pegloticase Khanna D, Fitzgerald JD, Khanna PP, et al. Arthritis Care Res. 2012;64(10):1431 1446. 4/12/2016 12 6

Desired Outcomes Achieve rapid and effective pain relief > 20% improvement within 24 hours, > 50% reduction at 24 hours Reduce SUA level < 6 mg/dl, and often < 5 mg/dl in severe cases Maintain joint function Prevent disease complications Avoid treatment-related adverse effects Provide cost-effective therapy Improve quality of life 4/12/2016 13 Khanna D, Fitzgerald JD, Khanna PP, et al. Arthritis Care Res. 2012;64(10):1431 1446. Management of Acute Attacks NSAIDs, colchicine, corticosteroids 4/12/2016 15 7

General Principals for Acute Management Start treatment as soon as possible Preferably within several hours of symptom onset Improved outcomes with early treatment (ie, within 24 hours) Continue treatment for duration of attack Few days to several weeks Reduce dose (not frequency) with significant reduction in symptoms Discontinue therapy within 1-3 days of complete attack resolution Exception: Slowly taper to discontinue glucocorticoids Urate lowering therapy is no benefit Continue without interruption, but generally do not initiate 4/12/2016 16 NSAIDs Recommended for most patients able to take oral therapy Any nonselective NSAID preferred Dose at higher end of therapeutic range Examples: Naproxen 500 mg po BID or indomethacin 50 mg po TID Selective NSAID as alternative Celecoxib 800 mg po x 1 400 mg po BID Few high-quality randomized controlled trials (RCTs) comparing NSAIDs 4/12/2016 17 8

NSAIDs Contraindications CKD (CrCl < 60 ml/min), active duodenal or gastric ulcer, CVD (hypertension or heart failure), allergy, anticoagulant therapy Adverse reactions Uncommon with brief course of therapy Gastrointestinal intolerance Use proton pump inhibitor in those at increased risk Worsening renal function 4/12/2016 18 Conaghan PG, Day RO. Drug Saf Int J Med Toxicol Drug Exp. 1994;11(4):252 258 Colchicine (Colcrys ) Recommended for patients able to take oral therapy, but with contraindication to NSAIDs Moderate to severe CKD, peptic ulcer disease, NSAID-intolerance 1.2 mg po x 1 0.6 mg po 1 hour later FDA approved dose for first 24 hours Only indicated if given within first 36 hours of attack ~2/3 respond if given within first 24 hours of symptoms Continue regimen after significant response (12 hours later) 0.6 mg po daily or BID until resolution 4/12/2016 19 Terkeltaub RA, Furst DE, Bennett K, et al. Arthritis Rheum. 2010;62(4):1060 1068. doi:10.1002/art.27327. Colcrys (colchicine) [product information]. http://dailymed.nlm.nih.gov/ Accessed February 10, 2016. 9

Colchicine (Colcrys ) Dose reduction for CrCl < 30 ml/min No RCTs compare NSAIDs to colchicine Contraindications Colchicine prophylaxis within 14 days with renal/hepatic impairment CYP3A4 or p-glycoprotein inhibitors in renal/hepatic impairment Cyclosporine, verapamil, diltiazem, erythromycin, and clarithromycin (among others) inhibit both pathways Colchicine dose reduction/frequency limits for those with normal organ function Caution with drug interactions 4/12/2016 20 Colcrys (colchicine) [product information]. http://dailymed.nlm.nih.gov/ Accessed February 10, 2016. Colchicine (Colcrys ) Adverse reactions Gastrointestinal symptoms Diarrhea, nausea, vomiting, and abdominal cramping Reversible peripheral neuropathy Reduced risk with low-dose regimen Colchicine toxicity Rare, but life threating and potentially fatal Blood cytopenias (usually neutropenia), rhabdomyolysis/myopathy, peripheral neuropathy, liver failure, sever cutaneous eruption 4/12/2016 21 Colcrys (colchicine) [product information]. http://dailymed.nlm.nih.gov/ Accessed February 10, 2016. 10

Corticosteroids For those with contraindication to NSAIDs and colchicine Various routes available: Intraarticular, oral, and systemic Intraarticular Only 1-2 actively inflamed joints Avoid if no prior diagnosis of gout established by joint aspiration Must exclude infection and expertise with technique required Triamcinolone acetonide (or methylprednisolone acetate equivalent dose ) 40 mg (large joint-knee), 30 mg (medium joint-wrist, ankle, elbow), 10 mg (small joint) Limited evidence, but highly effective and work quickly (ie, within 24 hours) 4/12/2016 22 Treatment of Acute Gout. http://www.uptodate.com/contents/treatment-of-acute-gout Accessed Feb 10, 2016 Corticosteroids Oral Polyarticular disease Prednisone or prednisolone 0.5 mg/kg po daily for 5-10 days, followed by abrupt discontinuation Full dose therapy for 2-5 days with a 7- to 10-day taper to discontinue Caution in heart failure, poorly controlled hypertension, glucose intolerance Clinical experience suggests safety and efficacy, similar efficacy as NSAIDs Adverse events Mood changes, hyperglycemia, increased blood pressure, and fluid retention Parenteral Methylprednisolone IV/IM or triamcinolone acetate IM 4/12/2016 23 Treatment of Acute Gout. http://www.uptodate.com/contents/treatment-of-acute-gout Accessed Feb 10, 2016 11

Combination Therapy For severe polyarticular attacks, particularly attacks involving multiple large joints, or when low-dose colchicine is ineffective Colchicine + NSAID Colchicine + oral corticosteroid Intraarticular corticosteroid injections + any other first-line agent (NSAID, colchicine, oral corticosteroid) 4/12/2016 24 Urate Lowering Therapy (ULT) for Prophylaxis Allopurinol, febuxostat, probenecid, pegloticase 4/12/2016 25 12

ULT Criteria For Use Recurrent attacks ( 2 per year) Evidence of tophus or tophi CKD stage 2 or worse Past urolithiasis Asymptomatic hyperuricemia is not an indication for treatment 4/12/2016 26 Khanna D, Fitzgerald JD, Khanna PP, et al. Arthritis Care Res. 2012;64(10):1431 1446. Xanthine Oxidase Inhibitors (XOI) Allopurinol and febuxostat 4/12/2016 27 13

Allopurinol First-line ULT Initial dose based on renal function 100 mg po daily with normal renal function 50 mg po daily with CrCl l< 30 ml/min Titrate every 2 to 5 weeks as needed and tolerated SUA goal < 6 mg/dl Maximum dose 800 mg po daily 4/12/2016 28 Khanna D, Fitzgerald JD, Khanna PP, et al. Arthritis Care Res. 2012;64(10):1431 1446. Allopurinol Adverse reactions Nausea and diarrhea occur uncommonly Generalized, maculopapular rash in ~2% of patients Allopurinol hypersensitivity syndrome (AHS) Most serious, but rare (HLA)-B*5801 testing is recommended for patients at an elevated risk Drug interactions Increased effects of theophylline and warfarin Inhibition of azathioprine and 6-mercaptopurine metabolism Reduce doses by 75% with allopurinol co-therapy Increased risk of skin rashes with ampicillin 4/12/2016 29 Zyloprim (allopurinol) [product information]. http://dailymed.nlm.nih.gov/ Accessed Feb. 10, 2016. 14

Febuxostat (Uloric ) First-line ULT Substitute for allopurinol intolerance or failure, cost concerns Dose: 40 mg po once daily initially Increase to 80 mg po once daily if SUA not < 6 mg/dl after 2 weeks No dosage adjustment with mild or moderate renal impairment Adverse reactions Nausea, arthralgias, rash, and transient elevation of hepatic transaminases Liver function tests at baseline, 2 and 4 months after initiation, and then periodically Cross-reaction in patients with a history of AHS not expected 4/12/2016 30 Khanna D, Fitzgerald JD, Khanna PP, et al. Arthritis Care Res. 2012;64(10):1431 1446. Uloric (febuxostat) [product information]. http://dailymed.nlm.nih.gov/ Accessed Feb.10, 2016. Uricosuric Agents Probenecid Alternative first-line, may be combined with XOI Dose: 250 mg po BID for 1 week, then 500 mg po BID May increase by 500 mg po every 4 weeks to achieve SUA < 6 mg/dl Maximum dose 2 g po daily Contraindications: History of urolithiasis or urate nephropathy, CrCl < 50 ml/min Adverse effects: Nausea, fever, rash, and rarely, hepatic toxicity Losartan and fenofibrate Mild uricosuric effects Appropriate in patients with hypertension or dyslipidemia, respectively 4/12/2016 31 Khanna D, Fitzgerald JD, Khanna PP, et al. Arthritis Care Res. 2012;64(10):1431 1446. Benemid (probenecid) [product information]. http://dailymed.nlm.nih.gov/ Accessed Feb 10, 2016. 15

Pegloticase (Krystexxa ) Reserved for refractory cases only Recombinant form of uricase 8 mg IV infusion over at least 2 hours once every 2 weeks Optimal duration unknown Significant adverse effects Gout flares, infusion reactions, anaphylaxis (in up to 5% of patients) Pretreatment with antihistamines and corticosteroids required Contraindicated in patients with G6PD deficiency 4/12/2016 32 Khanna D, Fitzgerald JD, Khanna PP, et al. Arthritis Care Res. 2012;64(10):1431 1446. Sundy JS, Becker MA, Baraf HS, et al. Arthritis Rheum. 2008;58(9):2882 2891. Flare Prophylaxis Need to protect against acute attacks when ULT is initiated Continue 6 months or up to 3 to 6 months after no evidence of gout activity and the target SUA has been achieved Risk of precipitating attack continues for ~ 12 months Colchicine 0.6 mg po once or twice daily Severe renal impairment: Starting dose should be 0.3 mg po daily NSAIDs Low dose Naproxen 250 mg po BID May combine with acid suppressing therapy Low-dose prednisone or prednisolone (< 10 mg/day) is an alternative 4/12/2016 34 16

Outcome Evaluation and Monitoring Acute gout Pain relief and decreased swelling of the affected joint(s) within 48 hours Adverse reactions to treatment Urate lowering therapy Monitor SUA every 2-5 weeks Gradually titrate agent to achieve and maintain target < 6 mg/dl Assess for new gouty arthritis attacks or development of tophi Adverse reactions to treatment 4/12/2016 35 Khanna D, Fitzgerald JD, Khanna PP, et al. Arthritis Care Res. 2012;64(10):1431 1446. Emerging Pharmacological Approaches Acute attacks Corticotrophin (Adrenocorticotropic hormone [ACTH]) Interluekin-1 inhibitors: anakinra (Kineret ) and canakinumab (Ilaris ) SQ Chronic prophylaxis Lesinurad (Zurampic ) Approved in December 2015 FDA approves Zurampic to treat high blood uric acid levels associated with gout. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm478791.htm Accessed Feb. 10, 2016 4/12/2016 36 17

Lesinurad (Zurampic ) Inhibits function of transporter proteins involved in uric acid reabsorption Promotes renal excretion of uric acid Recommended in combination with a XOI in those who fail to respond to XOI therapy alone Safety and efficacy evaluated in 3 RCTs Dose: 200 mg po once daily (with allopurinol or febuxostat) Avoid if CrCl < 45 ml/min Adverse reactions: Headache, influenza, increased blood creatinine, gastroesophageal reflux disease, and boxed warning FDA approves Zurampic to treat high blood uric acid levels associated with gout. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm478791.htm Accessed Feb. 10, 2016 Zurampic (lesinurad)[product information]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207988lbl.pdf Accessed Feb. 10, 2016 4/12/2016 37 Patient Counseling Minimization of risk factors and adherence to lifestyle modifications Dietary items to avoid, limit and encourage Limit purine-rich meat and seafood, high fructose corn syrup sweetened soft drinks and energy drinks, and alcohol Encourage consumption of low-fat/nonfat dairy products and vegetables Weight loss for obese patents to achieve healthy BMI Exercise Hydration Smoking cessation Co-morbid disease state management 4/12/2016 38 Khanna D, Fitzgerald JD, Khanna PP, et al. Arthritis Care Res. 2012;64(10):1431 1446. 18

Patient Counseling Benefits of drug therapy adherence Prevention of acute attacks and chronic complications Reinforce in those with resistant disease Drug interaction prevention NSAIDs and anticoagulants Colchicine with CYP3A4 and p-glycoprotein inhibitors Various allopurinol interactions Recommend physician referral Initial diagnosis Increase in frequency/intensity of acute attacks 4/12/2016 39 Summary Gout is a common condition encountered in primary care with a rising incidence The American College of Rheumatology provides recommendations for both acute management and chronic prophylaxis NSAIDs, colchicine, and corticosteroids are used for acute attacks ULT with allopurinol or febuxostat is first-line for attack prevention Emerging agents provide promise for improved disease control Effective patient education and lifestyle interventions are crucial 4/12/2016 40 19

Questions? 4/12/2016 41 20

Exam Questions 1. Which joint is most commonly affected in a middle-aged patient presenting with an acute gout attack? a. Wrist b. Knee c. Metatarsophalangeal d. Elbow 2. Which of the following is NOT typically considered a long-term consequence of gout and hyperuricemia? a. Joint destruction b. Liver disease c. Tophi d. Nephropathy 3. What organization has published the most recent and practical guideline for the management of gout? a. American College of Rheumatology (ACR) b. European League Against Rheumatism (EULAR) c. The British Society for Rheumatology (BSR) d. American College of Cardiology (ACC) 4. Which regimen is most appropriate to recommend for acute attack management in an otherwise healthy patient? a. Celecoxib 800 mg po BID b. Naproxen 500 mg po BID c. Colchicine 1.2 mg po x 1 dose only d. Indomethacin 50 mg po once daily

5. The most severe, but rare side effect of allopurinol therapy is. a. Nausea b. Mild rash c. Allopurinol hypersensitivity syndrome (AHS) d. Diarrhea 6. What is the minimum serum uric acid (SUA) goal in a patient with gout treated with urate lowering therapy? a. < 4 mg/dl b. < 10 mg/dl c. < 6 mg/dl d. < 8 mg/dl 7. When indicated, what agent is recommended first-line for serum urate-lowering? a. Fenofibrate b. Fuboxostat c. Probenecid d. Pegloticase 8. When counseling a patient whom, despite taking Allopurinol 300 mg daily, still has several acute attacks yearly regarding what more can be done to prevent attacks, all of the following are appropriate options except: a. increase the dose of allopurinol to a maximum of 800 mg/day b. add lesinurad (Zurampic ) for chronic prevention c. counsel on long term lifestyle modifications (weight loss, hydration, limit alcohol, etc.) d. use a heating pad on the affected joints 9. Which patient counseling point is an appropriate recommendation for a beneficial lifestyle modification in gout management? a. Limit the use of alcohol, especially beer b. Increase intake of foods such as liver and kidney meat c. Weight loss is recommended, regardless of body mass index (BMI) d. Ice affected joints daily to prevent attacks

10. Patients prescribed allopurinol therapy should be counseled regarding the risk of a drug interaction with which agent? a. Warfarin b. Cimetidine c. Furosemide d. Losartan