August 31, 2015

Krystexxa




Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Anaphylaxis

During pre-marketing controlled clinical trials, anaphylaxis was reported with a frequency of 6.5% of patients treated with KRYSTEXXA every 2 weeks, compared to none with placebo. Manifestations included wheezing, peri-oral or lingual edema, or hemodynamic instability, with or without rash or urticaria. Cases occurred in patients being pre-treated with one or more doses of an oral antihistamine, an intravenous corticosteroid and/or acetaminophen. This pre-treatment may have blunted or obscured symptoms or signs of anaphylaxis and therefore the reported frequency may be an underestimate. [See ADVERSE REACTIONS]

KRYSTEXXA should be administered in a healthcare setting by healthcare providers prepared to manage anaphylaxis. Patients should be pre-treated with antihistamines and corticosteroids. 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. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA. Patients should be informed of the symptoms and signs of anaphylaxis and instructed to seek immediate medical care should anaphylaxis occur after discharge from the healthcare setting.

The risk of anaphylaxis is higher in patients whose uric acid level increases to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed. Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL. Because of the possibility that concomitant use of oral urate-lowering therapy and KRYSTEXXA may potentially blunt the rise of serum uric acid levels, it is recommended that before starting KRYSTEXXA patients discontinue oral urate-lowering medications and not institute therapy with oral urate-lowering agents while taking KRYSTEXXA.

Infusion Reactions

During pre-marketing controlled clinical trials, infusion reactions were reported in 26% of patients treated with KRYSTEXXA 8 mg every 2 weeks, and 41% of patients treated with KRYSTEXXA 8 mg every 4 weeks, compared to 5% of patients treated with placebo. These infusion reactions occurred in patients being pre-treated with an oral antihistamine, intravenous corticosteroid and/or acetaminophen. This pre-treatment may have blunted or obscured symptoms or signs of infusion reactions and therefore the reported frequency may be an underestimate. [See ADVERSE REACTIONS]

KRYSTEXXA should be administered in a healthcare setting by healthcare providers prepared to manage infusion reactions. Patients should be pre-treated with antihistamines and corticosteroids. KRYSTEXXA should be infused slowly over no less than 120 minutes. In the event of an infusion reaction, the infusion should be slowed, or stopped and restarted at a slower rate.

The risk of infusion reaction is higher in patients whose uric acid level increases to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed. Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL. Because of the possibility that concomitant use of oral urate-lowering therapy and KRYSTEXXA may potentially blunt the rise of serum uric acid levels, it is recommended that before starting KRYSTEXXA patients discontinue oral urate-lowering medications and not institute therapy with oral urate-lowering agents while taking KRYSTEXXA.

Gout Flares

Gout flares may occur after initiation of KRYSTEXXA. [see ADVERSE REACTIONS] An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. 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. KRYSTEXXA does not need to be discontinued because of a gout flare. The gout flare should be managed concurrently as appropriate for the individual patient. [see DOSAGE AND ADMINISTRATION]

Congestive Heart Failure

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

Re-treatment With KRYSTEXXA

No controlled trial data are available on the safety and efficacy of re-treatment with KRYSTEXXA after stopping treatment for longer than 4 weeks. Due to the immunogenicity of KRYSTEXXA, patients receiving re-treatment may be at increased risk of anaphylaxis and infusion reactions. Therefore, patients receiving re-treatment after a drug-free interval should be monitored carefully. [see ADVERSE REACTIONS]

Patient Counseling Information

See Medication Guide

General Information

Provide and instruct patients to read the accompanying Medication Guide before starting treatment and before each subsequent treatment.

Anaphylaxis and Infusion Reactions
  • Anaphylaxis and infusion reactions can occur at any infusion while on therapy. Counsel patients on the importance of adhering to any prescribed medications to help prevent or lessen the severity of these reactions.
  • Educate patients on the signs and symptoms of anaphylaxis, including wheezing, peri-oral or lingual edema, hemodynamic instability, and rash or urticaria.
  • Educate patients on the most common signs and symptoms of an infusion reaction, including urticaria (skin rash), erythema (redness of the skin), dyspnea (difficulty breathing), flushing, chest discomfort, chest pain, and rash.
  • Advise patients to seek medical care immediately if they experience any symptoms of an allergic reaction during or at any time after the infusion of KRYSTEXXA. [see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS]
  • Advise patients to discontinue any oral urate-lowering agents before starting on KRYSTEXXA and not to take any oral urate-lowering agents while on KRYSTEXXA.
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

Inform patients not to take KRYSTEXXA if they have a condition known as G6PD deficiency. Explain to patients that G6PD deficiency is more frequently found in individuals of African or Mediterranean ancestry and that they may be tested to determine if they have G6PD deficiency, unless already known. [See CONTRAINDICATIONS]

Gout Flares

Explain to patients that gout flares may initially increase when starting treatment with KRYSTEXXA, and that medications to help reduce flares may need to be taken regularly for the first few months after KRYSTEXXA is started. [see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS] Advise patients that they should not stop KRYSTEXXA therapy if they have a flare.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of pegloticase.

The genotoxic potential of pegloticase has not been evaluated.

There was no evidence of impairment on fertility at pegloticase doses up to 40 mg/kg (approximately 50 times the MRHD on mg/m² basis) every other day in rats.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of KRYSTEXXA in pregnant women. KRYSTEXXA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pegloticase was not teratogenic in rats and rabbits at approximately 50 and 75 times the maximum recommended human dose (MRHD), respectively (on a mg/m² basis at maternal doses up to 40 and 30 mg/kg twice weekly, in rats and rabbits, respectively). Statistically significant decreases in mean fetal and pup body weights were observed at approximately 50 and 75 times the MRHD respectively (on a mg/m² basis at maternal doses up to 40 and 30 mg/kg every other day, in rats and rabbits, respectively). No effects on mean fetal body weights were observed at approximately 10 and 25 times the MRHD in rats and rabbits, respectively (on a mg/m² basis at maternal doses up to 10 mg/kg twice weekly in both species).

Nursing Mothers

It is not known whether this drug is excreted in human milk. Therefore KRYSTEXXA should not be used when breastfeeding unless the clear benefit to the mother can overcome the unknown risk to the newborn/infant.

Pediatric Use

The safety and effectiveness of KRYSTEXXA in pediatric patients less than 18 years of age have not been established.

Geriatric Use

Of the total number of patients treated with KRYSTEXXA 8 mg every 2 weeks in the controlled studies, 34% (29 of 85) were 65 years of age and older and 12% (10 of 85) were 75 years of age and older. No overall differences in safety or effectiveness were observed between older and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No dose adjustment is needed for patients 65 years of age and older.

Renal Impairment

No dose adjustment is required for patients with renal impairment. A total of 32% (27 of 85) of patients treated with KRYSTEXXA 8 mg every 2 weeks had a creatinine clearance of ≤ 62.5 mL/min. No overall differences in efficacy were observed.

Last reviewed on RxList: 8/7/2015
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions

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