YOUR GUIDE TO INFUSING KRYSTEXXA

KRYSTEXXA is an infusion drug, and like all infusion drugs, there are steps that your office needs to take to prepare your patients for infusion, and to ensure that KRYSTEXXA is administered properly.

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PROCESS FOR NEW PATIENTS

STEP 1: IDENTIFY SITE OF CARE AND SUBMIT SERVICE REQUEST FORM (SEE BELOW)

Initiates enrollment into KRYSTEXXAConnect services, including PATIENT ACCESS MANAGER

Within 2 business days:

You receive an Initial Summary of Benefits and your patient receives a Welcome Kit

STEP 2: CONFIRM NORMAL G6PD* ACTIVITY FROM LAB TESTS AND THAT URATE-LOWERING THERAPIES HAVE BEEN DISCONTINUED

If using an Alternate Site of Care (ASOC), refer to ASOC Letter Template (see below)

STEP 3: INFUSE WITH KRYSTEXXA

Perform preinfusion sUA test, preferably within 48 hours prior to each infusion (with exception of the first infusion)

Predictive biomarker for infusion reactions risk and product efficacy

Infusion

2-hour infusion (minimum)

1 hour of observation (recommended)

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KRYSTEXXAConnect Enrollment Form

Starting a patient on KRYSTEXXA? Get them connected to their Patient Access Manager faster by completing this enrollment form.

DOWNLOAD FORM
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Alternate Site of Care Letter – Template

Download the following resource to recommend infusion of KRYSTEXXA. This template is a suggestion and should be printed on the physician’s letterhead. The physician is responsible for completing this letter in a way that completely and accurately represents a patient’s circumstances.

DOWNLOAD LETTER DOWNLOAD INSTRUCTIONS
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Preinfusion Medications

Download this guide to see if your patients should take an antihistamine, analgesic, or IV corticosteroid prior to infusing KRYSTEXXA.

DOWNLOAD GUIDE

STEPS TO A SUCCESSFUL INFUSION DAY

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Infusion Checklist

Make sure you perform every step of the infusion process for KRYSTEXXA by downloading the Infusion Checklist.

DOWNLOAD CHECKLIST
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Infusion Protocol

Download and fill out this infusion protocol template to give preinfusion medication and infusion instructions to an Alternate Site of Care.

DOWNLOAD TEMPLATE Full Prescribing Information
STEP 1: CONFIRM

Prior to the first infusion, confirm the patient has normal G6PD* activity from lab tests and has discontinued taking urate-lowering therapies (eg, allopurinol, febuxostat)

Do not administer KRYSTEXXA to patients with G6PD deficiency

Prior to each subsequent infusion, confirm sUA level was tested in the last 48 hours, beginning after the first infusion. Notify prescribing healthcare provider (HCP) if sUA level has not been tested or if any preinfusion sUA level is ≥6 mg/dL, and consider discontinuing therapy, particularly after 2 preinfusion sUA levels are >6 mg/dL. See Stopping Rules

STEP 2: COUNSEL

Answer any questions the patient may have regarding treatment and provide a Medication Guide

Remind the patient that they may have gout flares, and KRYSTEXXA therapy can be continued regardless of gout flares

A Patient Access Manager (PAM) is available to support the patient throughout therapy

STEP 3: PREPARE AND ADMINISTER

Administer preinfusion medications per prescribing HCP’s orders. See Prescribing Information

Visually inspect vial for particulate matter and ensure solution is clear and colorless

Using aseptic technique, withdraw 1 mL into a sterile syringe and inject into a 250 mL bag of normal or half-normal saline. Gently mix the bag by inverting several times and discard any unused portion of the remaining product. Do not shake

No loading dose recommended or required

KRYSTEXXA is a single-dose vial

The diluted solution should be used within 4 hours

Before administration, allow the diluted solution of KRYSTEXXA to reach room temperature

Artificial heating should not be used

If not administered immediately, it is recommended that the diluted solution should be stored in the refrigerator and away from light

Initiate infusion at a rate of 125 mL/h or slower via infusion pump or gravity feed

Infuse over no less than 2 hours
DO NOT ADMINISTER AS INTRAVENOUS PUSH OR BOLUS

Use your normal protocol to monitor for infusion reactions

In the event of an infusion reaction, as clinically indicated, the infusion can be slowed or stopped and restarted at a slower rate

STEP 4: OBSERVE AND REMIND

Observe the patient for approximately 1 hour post-infusion

Remind the patient of their next sUA test and KRYSTEXXA infusion appointments

KRYSTEXXA should be given every 2 weeks—it is recommended to provide a standing order to the lab to check the patient’s sUA level prior to each infusion

*KRYSTEXXA is contraindicated for patients with G6PD deficiency. G6PD deficiency is an abnormally low level of glucose-6-phosphate dehydrogenase. Patients of African, Mediterranean, and Southern Asian ancestry have a higher risk of deficiency.3

Available through Group Purchasing Organization (GPO) wholesalers and specialty pharmacies, depending on patient benefit design.

References
  1. Baraf HS, Becker MA, Gutierrez-Urena SR, et al. Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy. Arthritis Res Ther. 2013;15(5):R137.
  2. Sundy JS, Baraf HS, Yood RA, et al. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA. 2011;306(7):711-720.
  3. KRYSTEXXA [prescribing information]. Horizon Pharma Rheumatology LLC. September 2016.
  4. Thiele RG, Schlesinger N. Diagnosis of gout by ultrasound. Rheumatology (Oxford). 2007;46(7):1116-1121.
  5. Rees F, Hui M, Doherty M. Optimizing current treatment of gout. Nat Rev Rheumatol. 2014;10(5):271-283.
  6. Naredo E, Uson J, Jiménez-Palop M, et al. Ultrasound-detected musculoskeletal urate crystal deposition: which joints and what findings should be assessed for diagnosing gout? Ann Rheum Dis. 2014;73(8):1522-1528.
  7. Dalbeth N, House ME, Horne A, Taylor WJ. Reduced creatinine clearance is associated with early development of subcutaneous tophi in people with gout. BMC Musculoskelet Disord. 2013;14:363.
  8. Dalbeth N, Pool B, Gamble GD, et al. Cellular characterization of the gouty tophus: a quantitative analysis. Arthritis Rheum. 2010;62(5):1549-1556.
  9. Doghramji PP, Wortmann RL. Hyperuricemia and gout: new concepts in diagnosis and management. Postgrad Med. 2012;124(6):98-109.
  10. Bongartz T, Glazebrook KN, Kavros SJ, et al. Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study. Ann Rheum Dis. 2015;74(6):1072-1077.
  11. Schett G, Schauer C, Hoffmann M, Hermann M. Why does the gout attack stop? A roadmap for the immune pathogenesis of gout. RMD Open. 2015;1:(suppl 1):e000046.
  12. Edwards NL. Gout A. Clinical features. In: Klippel JH, Stone JH, Crofford LJ, White PH, eds. Primer on the Rheumatic Diseases. 13th ed. New York, NY: Springer; 2008:241-249.
  13. Edwards NL. Crystal-induced joint disease. In: Nabel EG. ACP Medicine: A Publication of the American College of Physicians. Hamilton, Ontario: Decker Intellectual Properties; 2012:1-16.
  14. Yu KH, Lien LC, Ho HH. Limited knee joint range of motion due to invisible gouty tophi. Rheumatology (Oxford). 2004;43(2):191-194.
  15. Dalakas MC. Inflammatory muscle diseases. N Engl J Med. 2015;372:1734-1747.
  16. Ianuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007;357:2153-2165.
  17. Parsad K, Rath D, Kundu BK. Arthritis Robustus: review of a case of an "abnormal" rheumatoid. Springerplus. 2014 Oct 16;3:606.
  18. Rada B. Neutrophil extracellular traps and microcrystals. J Immunol Res. 2017;2017:2896380.
  19. McQueen FM, Doyle A, Reeves Q, et al. Bone erosions in patients with chronic gouty arthropathy are associated with tophi but not bone oedema or synovitis: new insights from a 3 T MRI study. Rheumatology (Oxford). 2014;53(1):95-103.
  20. Choi HK, Al-Arfaj AM, Eftekhari A, et al. Dual energy computed tomography in tophaceous gout. Ann Rheum Dis. 2009;68(10):1609-1612.
  21. Park JJ, Roudier MP, Soman D, Mokadam NA, Simkin PA. Prevalence of birefringent crystals in cardiac and prostatic tissues, an observational study. BMJ Open. 2014;4(7):e005308.
  22. Popovich I, Dalbeth N, Doyle A, Reeves Q, McQueen FM. Exploring cartilage damage in gout using 3-TMRI: distribution and associations with joint inflammation and tophus deposition. Skeletal Radiol. 2014;43(7):917-924.
  23. Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431-1446.
  24. Perez-Ruiz F. Treating to target: a strategy to cure gout. Rheumatology (Oxford). 2009;48(suppl 2):ii9–ii14.
  25. Araujo EG, Bayat S, Petsch C, et al. Tophus resolution with pegloticase; a prospective dual-energy CT study. RMD Open. 2015;1(1):e000075.
  26. Schumacher HR, Becker MA, Wortmann RL, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008;59(11):1540-1548.
  27. Data on file. Horizon Pharma Rheumatology LLC; 2016.
  28. Baraf HS, Yood RA, Ottery FD, Sundy JS, Becker MA. Infusion-related reactions with pegloticase, a recombinant uricase for the treatment of chronic gout refractory to conventional therapy. J Clin Rheumatol. 2014;20(8):427-432.
  29. McDonagh EM, Thorn CF, Callaghan JT, Altman RB, Klein TE. PharmGKB summary: uric acid-lowering drugs pathway, pharmacodynamics. Pharmacogenet Genomics. 2014;24(9):464–476.
  30. Terkeltaub R, Bushinsky DA, Becker MA. Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics. Arthritis Res Ther. 2006;8(suppl 1):S4.
  31. Yood RA, Ottery FD, Irish W, Wolfson M. Effect of pegloticase on renal function in patients with chronic kidney disease: a post hoc subgroup analysis of 2 randomized, placebo-controlled, phase 3 clinical trials. BMC Res Notes. 2014;7:54.
  32. Levey AS, Bosch JP, Lewis JB, et al. Ann Intern Med. 1999;130(6):461-470.
  33. Levey AS, Stevens LA, Schmid CH, et al; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) [published correction appears in Ann Intern Med. 2011;155(6):408]. Ann Intern Med. 2009;150(9):604-612.
  34. Michels WM, Grootendorst DC, Verduijn M, et al. Clin J Am Soc Nephrol. 2010;5(6):1003-1009.
  35. Poggio ED, Wang X, Greene T, et al. J Am Soc Nephrol. 2005;16(2):459-466.
  36. Bleyer AJ, Wright D, Alcorn H. Pharmacokinetics and pharmacodynamics of pegloticase in patients with end-stage renal failure receiving hemodialysis. Clin Nephrol. 2015;83(5):286-292.
For U.S. Healthcare Professionals  |  Patient Site

Indications and Usage

KRYSTEXXA® (pegloticase) is indicated for the treatment of chronic gout in adult patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated.

Important Limitations of Use: KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia.

Important Safety Information

WARNING: ANAPHYLAXIS AND INFUSION REACTIONS

Anaphylaxis and infusion reactions have been reported to occur during and after administration of KRYSTEXXA. Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion. However, delayed-type hypersensitivity reactions have also been reported. KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions. Patients should be premedicated with antihistamines and corticosteroids. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA. Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.

CONTRAINDICATIONS: G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA

Screen patients for G6PD deficiency prior to starting KRYSTEXXA. Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. Do not administer KRYSTEXXA to these patients.

INDICATIONS AND USAGE

KRYSTEXXA® (pegloticase) is indicated for the treatment of chronic gout in adult patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated.

Important Limitations of Use: KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia.

IMPORTANT SAFETY INFORMATION

WARNING: ANAPHYLAXIS AND INFUSION REACTIONS

Anaphylaxis and infusion reactions have been reported to occur during and after administration of KRYSTEXXA. Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion. However, delayed-type hypersensitivity reactions have also been reported. KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions. Patients should be premedicated with antihistamines and corticosteroids. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA. Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.

The risk of anaphylaxis and infusion reactions is higher in patients who have lost therapeutic response.

Concomitant use of KRYSTEXXA and oral urate-lowering agents may blunt the rise of sUA levels. Patients should discontinue oral urate-lowering agents and not institute therapy with oral urate-lowering agents while taking KRYSTEXXA.

In the event of anaphylaxis or infusion reaction, the infusion should be slowed, or stopped and restarted at a slower rate.

Inform patients of the symptoms and signs of anaphylaxis, and instruct them to seek immediate medical care should anaphylaxis occur after discharge from the healthcare setting.

CONTRAINDICATIONS: G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA

Screen patients for G6PD deficiency prior to starting KRYSTEXXA. Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. Do not administer KRYSTEXXA to these patients.

GOUT FLARES

An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, including treatment with KRYSTEXXA. If a gout flare occurs during treatment, KRYSTEXXA need not be discontinued. Gout flare prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended starting at least 1 week before initiation of KRYSTEXXA therapy and lasting at least 6 months, unless medically contraindicated or not tolerated.

CONGESTIVE HEART FAILURE

KRYSTEXXA has not been studied in patients with congestive heart failure, but some patients in the clinical trials experienced exacerbation. Exercise caution when using KRYSTEXXA in patients who have congestive heart failure and monitor patients closely following infusion.

ADVERSE REACTIONS

The most commonly reported adverse reactions in clinical trials with KRYSTEXXA are gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis and vomiting.

Please see Full Prescribing Information and Medication Guide for more information.

INDICATIONS AND USAGE

KRYSTEXXA® (pegloticase) is indicated for the treatment of chronic gout in adult patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated.

Important Limitations of Use: KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia.

IMPORTANT SAFETY INFORMATION

WARNING: ANAPHYLAXIS AND INFUSION REACTIONS

Anaphylaxis and infusion reactions have been reported to occur during and after administration of KRYSTEXXA. Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion. However, delayed-type hypersensitivity reactions have also been reported. KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions. Patients should be premedicated with antihistamines and corticosteroids. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA. Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.

The risk of anaphylaxis and infusion reactions is higher in patients who have lost therapeutic response.

Concomitant use of KRYSTEXXA and oral urate-lowering agents may blunt the rise of sUA levels. Patients should discontinue oral urate-lowering agents and not institute therapy with oral urate-lowering agents while taking KRYSTEXXA.

In the event of anaphylaxis or infusion reaction, the infusion should be slowed, or stopped and restarted at a slower rate.

Inform patients of the symptoms and signs of anaphylaxis, and instruct them to seek immediate medical care should anaphylaxis occur after discharge from the healthcare setting.

CONTRAINDICATIONS: G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA

Screen patients for G6PD deficiency prior to starting KRYSTEXXA. Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. Do not administer KRYSTEXXA to these patients.

GOUT FLARES

An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, including treatment with KRYSTEXXA. If a gout flare occurs during treatment, KRYSTEXXA need not be discontinued. Gout flare prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended starting at least 1 week before initiation of KRYSTEXXA therapy and lasting at least 6 months, unless medically contraindicated or not tolerated.

CONGESTIVE HEART FAILURE

KRYSTEXXA has not been studied in patients with congestive heart failure, but some patients in the clinical trials experienced exacerbation. Exercise caution when using KRYSTEXXA in patients who have congestive heart failure and monitor patients closely following infusion.

ADVERSE REACTIONS

The most commonly reported adverse reactions in clinical trials with KRYSTEXXA are gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis and vomiting.

Please see Full Prescribing Information and Medication Guide for more information.