SAFETY STARTS WITH THE STOPPING RULES

The KRYSTEXXA sUA Stopping Rules were developed after a post hoc analysis of the pivotal clinical trials. Data showed a correlation between the preinfusion sUA level rising above 6 mg/dL and the occurrence of infusion reactions for patients already on KRYSTEXXA.1,2

Since 95% of infusion reactions occurred when sUA levels were >6 mg/dL, preinfusion sUA levels were determined to be a powerful predictive biomarker for those adverse events.*

Use these guidelines to help avoid anaphylaxis and other infusion reactions and ensure maximum safety.

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Full Prescribing Information

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STOPPING RULES: USE sUA AS A BIOMARKER TO REDUCE THE RISK OF INFUSION REACTIONS1,2

The KRYSTEXXA sUA Stopping Rules were based on the results of 852 infusions.

Incidence of infusion reactions per 100 infusions3

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INFUSION REACTIONS (IR) IN THE PHASE 3 CLINICAL TRIAL1

IR Frequency (%)
Hives 10.6
Chest discomfort 9.5
Chest pain 9.5
Reddening of the skin 9.5
Itching of the skin 9.5
Difficulty breathing 7.1

The majority of IRs in the clinical trial were resolved by slowing or interrupting the infusion and restarting at the same or a slower rate.3†

Approximately 75% of infusion reactions with a recorded intervention.

CHARACTERIZATION OF SEVERE IRs3

A total of 4 cases of severe IRs identified by investigators were retrospectively reclassified as anaphylaxis by the FDA (n=85).

PATIENT IR TREATMENT OUTCOME
1 Difficulty breathing, swelling of the tongue Infusion discontinued (Benadryl®: 25 mg IV) Resolved
2 Difficulty breathing, hives, elevated heart rate, elevated blood pressure Infusion discontinued (Benadryl®, Ventolin®, IV)
3 Itchy eye, puffy eye, chest discomfort, throat irritation, joint pain, back pain Infusion discontinued
4 Flushing, itchy skin, low blood pressure, elevated heart rate, hives Infusion discontinued (Benadryl®, Demerol®)
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Patient did not take full premedication regimen.

Of the 4 cases reclassified as anaphylaxis, 3 likely would have been prevented by using the KRYSTEXXA sUA Stopping Rules.4

In the pivotal clinical trials, no patients with infusion reactions required intubation, mechanical ventilator support, or hospitalization. There were no infusion-related deaths.3

SELECT IMPORTANT SAFETY INFORMATION

Patients should be premedicated with antihistamines and corticosteroids

Patients should discontinue oral urate-lowering agents while taking KRYSTEXXA

Patients treated with KRYSTEXXA experienced the following most common serious adverse events: gout flares, 77% (65/85); infusion reactions, 26% (22/85); and anaphylaxis, 5% (4/85) compared to patients treated with placebo: gout flares, 81% (35/43); infusion reactions, 5% (2/43); and anaphylaxis, 0%

References
  1. KRYSTEXXA [prescribing information]. Horizon Pharma Rheumatology LLC.
  2. Data on file. Horizon Pharma Rheumatology LLC; September 2016.
  3. Baraf HS, et al. J Clin Rheumatol. 2014;20(8):427-432.
  4. Data on file. Horizon Pharma Rheumatology LLC; May 2017.
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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.