A M B U L AT O RY C A S E P R E S E N TAT I O N

THE GOUTP R E S E N T E D BY: DA N T RA N

OBJECTIVES

By the end of this presentation, you should be able to:

• Sort the following 4 preferred treatments, in order of preference, for acute gout exacerbation: non-pharmacologic, NSAIDS, colchicine, and steroids

• Identify alternative drug treatment options for chronic gout in patients with severe renal insufficiency or who are refractory to conventional treatment.

SETTING

MTM and Medication Review Consult

New Patient to Franciscan Clinic• “Cold” Visit:• Reported chronic renal failure by referring physician. • No Prior Drug History, and no med list• No access to patient lab results

OVERVIEW OF CASE

• PMH: • History of renal insufficiency• Colon cancer (remission)• Anemia• Hip arthritis• Gout• Type 2 diabetes• Atrial fibrillation

• Chronic Conditions: • Gout • Edema• Diabetes • Hyperlipidemia• Glaucoma• hypothyroidism

• Clinical S/Sx: Remarkably able-bodied, appears obese, reports feeling healthy, complains about pain and tenderness in great toe

• SH: • Lives with husband in non-

smoking home. • Frequently gardens in

backyard. • Denies alcohol use.

“MM” is a 90 yr old caucasian female with recent hospital discharge following a “fall” incident.

MEDICATION THERAPY

Indication Drug Strength Dose Route Duration/Frequency

Gout Allopurinol 300 mg 1 tablet Po Daily

Hypertension Furosemide 20 mg 2 tablets Po Daily

Hyperlipidemia

Simvastatin 40 mg 1 tablet Po At bedtime

Thyroid Levothyroxine 125 mcg 1 tablet Po Daily

Diabetes

Glipizide XL 2.5 mg 1 tablet Po Daily

Metformin 500 mg 1 tablet Po Twice a day

Glaucoma

Timolol Maleate 0.5% 1 drop In both eyes Twice daily

Travoprost 0.004% 1 drop In both eyes At bedtime

PE Prophylaxis

Warfarin Sodium 3 mg 1 tablet Po Daily on Su/Tu/Th/Sa

Warfarin Sodium 2 mg 1 tablet Po Daily on Mon/Wed/Fri

Pain

Tramadol

25 mg 1 tablet Po Every 6 hours as needed(average 1 tab/day)

Acetaminophen 500 mg 1 capsule Po Every 4-6 hrs. as needed (average 1-2 tabs/week)

No reported herbals or other OTC products.

DRUG THERAPY EVALUATION

• Concerns:

1. Metformin appears to not be on her med drug list or hospitalization discharge paperwork list but was brought in her brown bag.

2. Allopurinol and Metformin both require assessment in cases of renal insufficiency.

3. Address the root cause behind pain in the patient’s great toe and to relieve her discomfort.

DRUG THERAPY EVALUATION

• Gout Evaluation:

Subjective/Objective

Evaluation

Presence of inflammation in the great toe indicative of “podagra”

Podagra is a common acute exacerbation of gout.

MM is taking allopurinol 300 mg for her gout

Allopurinol may build up and increase risk due to her renal function.

Dosing for pain meds are appropriate. MM reports mild usage of these drugs.

It appears that pain is adequately controlled with current tramadol and acetaminophen therapy.

GOUT: ETIOLOGY 1

• Acute arthritis associated with monosodium urate crystals in synovial fluid• Uric acid is a byproduct of xanthine oxidase in purine

metabolism

• Elevated serum urate concentration: hyperuricemia• Uric acid vs. Monosodium Urate

• Aggregates of crystals around joints can form tophi, which is painful and can cause deformity• Associated with:• Renal failure and renal tissue disease: underexcretion of

uric acid• Uric Acid nephrolithiasis

1. Pittman JR, Bross MH. Diagnosis and Management of Gout. Am Fam Physician 1999 Apr 1; 59(7):1799-1806

DIAGNOSIS OF GOUT

• Dx: 1977 ARA Criteria (any 6 of the following) 2 Etiology-related 1. Hyperuricemia

2. Monosodium urate microcrystals in joint fluid during attack

MM reports having these signs/symptoms

1. Redness observed over joints,2. Max inflammation developed in 1 day3. Monoarthritis attack,4. Unilateral first metatarsophalangeal joint

attack (great toe)5. >1 attack of acute arthritis

Unknown 1. Unilateral tarsal joint attack (ankle)2. Tophus3. Swelling within a joint on x-ray4. Joint fluid culture negative during attack.

Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yü T-F. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977;20:895-900.

2012 ACR GUIDELINES

1. Khanna D, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis care & research 64.10 (2012): 1431-1446.

2. Khanna D, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: Therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis care & research 64.10 (2012): 1447-1461.

ACUTE GOUT 1

• Goal: Stop the acute gout attack! • 1st Line: Non-Pharmacologic

• Reduce dietary intake of meals high in purines• Increase fluid intake, reduce salt intake• Apply ice to arthritic joints• Consider weight loss

• 2nd Line: NSAID• Indomethacin SR 75 mg BID until attack subsides. Alternatives:

naproxen and sulindac. Not appropriate for MM due to renal failure

• 3rd Line: Colchicine (PO)• Anti-mitotic drug, can cause GI effects (nausea, diarrhea)

• 4th Line: Steroids1. Pittman JR, Bross MH. Diagnosis and Management of Gout. Am Fam Physician 1999 Apr 1; 59(7):1799-1806

CHRONIC GOUT

• 2 or more attacks per year = Chronic Gout Therapy• Uricosuric Drug vs. Xanthine Oxidase Inhibitor • Probenecid

• Renal Dosing Consideration• Probenecid: contraindicated in patients with renal

insufficiency• Allopurinol 3 : • CrCl 20 ml/min : 100 mg po daily • CrCl 10 ml/min : 100 mg po every 2 days• CrCl 0 ml/min : 100 mg po every 3 days

• Correct underlying causes (secondary)

• .Allopurinol

3. Dalneth N, Stamp L. Allopurinol dosing in renal impairment: walking the tightrope between adequate urate lowering and adverse events. Semin Dial 2007; 20:391-5.

ALTERNATIVE TREATMENT?

• Uloric (febuxostat) 4 • Xanthine Oxidase inhibitor• Recommended starting dose: Uloric 40 mg once daily

• Eliminated by both hepatic and renal pathways 4 • “Use with caution” in patients with severe renal

impairment• Following multiple doses 80 mg doses in patients with

severe renal impairment (CrCl 10-29 ml/min), the Cmax of febuxostat did not change compared to patients with normal renal function.

4. Uloric [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc; 2012.

ALTERNATIVE TREATMENT?

• Krystexxa (pegloticase) 5 • PEGylated enzyme specific for uric acid• Administered as IV push or bolus. Requires discontinuation of oral

urate-lowering agents before starting therapy.• No dose adjustment for renal or hepatic impairment

• Indicated for adult patients refractory to conventional therapy• Rapidly resolves gouty deposits and dramatically lowers uric acid

levels.• Severe infusion reactions (41%), gout flares, possibly worsen CHF.

• Price: Allopurinol $100/yr , Uloric $2000/yr Krystexxa $20,000/year

Krystexxa [package insert]. East Brunswick, NJ: Savient Pharmaceuticals, Inc.; 2010.

MM’S CARE PLAN

• Recommend non-pharmacological therapy (1st line) • Acute gouty arthritis appears to be mild and pain is well-

controlled with current non-opiate therapy.• Patient education to ice joint and reduce purine intake.

• Get labs; reassess renal function. • Possibly consider changing therapy to Uloric (febuxostat)

40mg orally once daily if renal function worsens.

CARE PLAN

• Monitor: Inflammation, worsening of symptoms of hyperuricemia including joint pain or podagra, renal function.

• Efficacy: reduction/resolution of acute gout symptoms.

• Toxicity: monitor for worsening symptoms, hyperuricemia, reduction in renal function (SCr, CrCl

SUMMARY OF KEY POINTS

• Gout is a heterogeneous group of diseases associated with monosodium urate crystals in synovial fluid and arthritic joint attack.

• Acute gout exacerbation is primarily handled with non-pharmacological treatment, then NSAIDS, colchicine, and steroids.

• Renal Insufficiency is a key concern related to most common chronic gout treatments: Uricosuric drugs and Xanthine Oxidase inhibitors (except Uloric).

QUIZ TIME!

• MM’s doctor asks you for an alternative drug treatment option instead of allopurinol for MM’s chronic gout due to her severe renal insufficiency. What other drug can you suggest?

• 1. Probenecid• 2. Uloric• 3. Zyloprim• 4. There are no alternatives.

THE ANSWER IS A B C D. JUST NOT IN THAT ORDER.

• Sort the following 4 preferred treatments, in order of preference, for acute gout exacerbation:

A. Colchicine B. Non-pharmacologicC. NSAIDS D. Steroids Order: ____ , _____ , _____ , _____

REFERENCES

1. Pittman JR, Bross MH. Diagnosis and Management of Gout. Am Fam Physician 1999 Apr 1; 59(7):1799-1806

2. Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yü T-F. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977;20:895-900.

3. Dalneth N, Stamp L. Allopurinol dosing in renal impairment: walking the tightrope between adequate urate lowering and adverse events. Semin Dial 2007; 20:391-5.

4. Uloric [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc; 2012.

5. Khanna D, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis care & research 64.10 (2012): 1431-1446.

6. Khanna D, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: Therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis care & research 64.10 (2012): 1447-1461.

7. Krystexxa [package insert]. East Brunswick, NJ: Savient Pharmaceuticals, Inc.; 2010.