KRYSTEXXA Solution for infusion (2020)
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Horizon Therapeutics USA, Inc.
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BOXED WARNING SECTION
<b>WARNING: ANAPHYLAXIS AND INFUSION REACTIONS; G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA</b> <b>Anaphylaxis and infusion reactions have been reported to occur during and after administration ...
1. Indications and Usage
KRYSTEXXA (pegloticase) is a PEGylated uric acid specific enzyme indicated for the treatment of chronic gout in adult patients refractory to conventional therapy. Gout refractory to conventional therapy ...
2. Dosage and Administration
2.1 Dosage The recommended dose and regimen of KRYSTEXXA for adult patients is 8 mg (uricase protein) given as an intravenous infusion every two weeks. The optimal treatment duration with KRYSTEXXA has ...
3. Dosage Forms and Strengths
KRYSTEXXA is a clear, colorless, sterile 8 mg/mL solution of pegloticase in a 2 mL single-dose vial, expressed as amounts of uricase protein. KRYSTEXXA must be diluted prior to use.
4. Contraindications
Glucose-6-phosphate dehydrogenase (G6PD) deficiency <em>[see Warnings and Precautions (5.3)]</em>
5. Warnings and Precautions
5.1 Anaphylaxis During pre-marketing clinical trials, anaphylaxis was reported with a frequency of 6.5% (8/123) of patients treated with KRYSTEXXA every 2 weeks and 4.8% (6/126) for the every 4-week dosing ...
6. Adverse Reactions
The following serious adverse reactions are discussed in greater detail in other sections of the label: Anaphylaxis <em>[see Warnings and Precautions (5.1)]</em> Infusion Reactions <em>[see Warnings and ...
6.1. Clinical Trials Experience
The data described below reflect exposure to KRYSTEXXA in patients with chronic gout refractory to conventional therapy in two replicate randomized, placebo-controlled, double-blind 6-month clinical trials: ...
6.2. Immunogenicity
Anti-pegloticase antibodies developed in 92% of patients treated with KRYSTEXXA every 2 weeks, and 28% for placebo. Anti-PEG antibodies were also detected in 42% of patients treated with KRYSTEXXA. High ...
6.3. Postmarketing Experience
The following adverse reactions have been identified during postapproval use of KRYSTEXXA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible ...
7. Drug Interactions
No studies of interactions of KRYSTEXXA with other drugs have been conducted. Because anti-pegloticase antibodies appear to bind to the PEG portion of the drug, there may be potential for binding with ...
8.1. Pregnancy
Risk Summary There are no adequate and well-controlled studies of KRYSTEXXA in pregnant women. Based on animal reproduction studies, no structural abnormalities were observed when pegloticase was administered ...
8.2. Lactation
Risk Summary 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 ...
8.4. Pediatric Use
The safety and effectiveness of KRYSTEXXA in pediatric patients less than 18 years of age have not been established.
8.5. 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 ...
8.6. 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 ...
10. Overdosage
No reports of overdosage with KRYSTEXXA have been reported. The maximum dose that has been administered as a single intravenous dose is 12 mg as uricase protein. Patients suspected of receiving an overdose ...
11. Description
KRYSTEXXA (pegloticase) is a uric acid specific enzyme which is a PEGylated product that consists of recombinant modified mammalian urate oxidase (uricase) produced by a genetically modified strain of ...
12.1. Mechanism of Action
KRYSTEXXA is a uric acid specific enzyme which is a recombinant uricase and achieves its therapeutic effect by catalyzing the oxidation of uric acid to allantoin, thereby lowering serum uric acid. Allantoin ...
12.2. Pharmacodynamics
Approximately 24 hours following the first dose of KRYSTEXXA, mean plasma uric acid levels for subjects in the KRYSTEXXA groups were 0.7 mg/dL for the KRYSTEXXA 8 mg every 2 weeks group. In comparison, ...
12.3. Pharmacokinetics
Pegloticase levels were determined in serum based on measurements of uricase enzyme activity. Absorption Following single intravenous infusions of 0.5 mg to 12 mg pegloticase in 23 patients with symptomatic ...
13.1. Carcinogensis, 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 ...
13.2. Animal Toxicology and/or Pharmacology
Pegloticase at similar to and higher than the maximum recommended human dose (MRHD) on a plasma AUC basis [at intravenous (IV) doses of ≥0.4 mg/kg in dogs] caused cytoplasmic vacuoles in multiple organs, ...
14. Clinical Studies
The efficacy of KRYSTEXXA was studied in adult patients with chronic gout refractory to conventional therapy in two replicate, multicenter, randomized, double-blind, placebo- controlled studies of six ...
16.1. How Supplied
KRYSTEXXA is supplied as a clear, colorless, sterile solution in phosphate buffered saline intended for intravenous infusion after dilution. KRYSTEXXA is supplied in a single-dose 2 mL glass vial with ...
16.2. Storage and Handling
Before the preparation for use, KRYSTEXXA must be stored in the carton and maintained at all times under refrigeration between 2° to 8°C (36° to 46°F). <b>Protect from light. Do not shake or freeze.</b> ...
17. Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). General Information Provide and instruct patients to read the accompanying Medication Guide before starting treatment and ...