ients' responses to other PEG-containing therapeutics is unknown.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C
A complete eva luation of the reproductive and developmental toxicity of pegloticase has not been completed. Adequate animal reproduction studies have not been conducted with KRYSTEXXA. It is not known whether KRYSTEXXA can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. There are no adequate and well-controlled studies in pregnant women. KRYSTEXXA should be used during pregnancy only if clearly needed.
Pegloticase was not teratogenic in rats administered 0, 5, 10, or 40mg/kg twice weekly by the intravenous route on gestation days6 through 16 (the doses are approximately 6-fold to 50-fold higher than the maximum recommended human dose (MRHD) of 8mg (0.133mg/kg based on a 60kg person) every 2weeks based on a mg/m2 comparison).
8.3 Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, it is not recommended to administer KRYSTEXXA to a nursing mother.
8.4 Pediatric Use
The safety and effectiveness of KRYSTEXXA in pediatric patients less than 18years of age have not been established.
8.5 Geriatric Use
Of the total number of patients treated with KRYSTEXXA 8mg every 2weeks in the controlled studies, 34% (29 of 85) were 65years of age and older and 12% (10 of 85) were 75years 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 65years of age and older.
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 8mg every 2weeks had a creatinine clearance of ≤62.5mL/min. No overall differences in efficacy were observed.
10 OVERDOSAGE
No reports of overdosage with KRYSTEXXA have been reported. The maximum dose that has been administered as a single intravenous dose is 12mg as uricase protein.
Patients suspected of receiving an overdose should be monitored, and general supportive measures should be initiated as no specific antidote has been identified.
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 Escherichia coli. Uricase is covalently conjugated to monomethoxypoly(ethylene glycol) [mPEG] (10kDa molecular weight). The cDNA coding for uricase is based on mammalian sequences. Each uricase subunit has a molecular weight of approximately 34kDa per subunit. The average molecular weight of pegloticase (tetrameric enzyme conjugated to mPEG) is approximately 540kDa.
KRYSTEXXA is intended for intravenous infusion.
KRYSTEXXA is a sterile, clear, colorless solution containing 8mg/mL pegloticase in phosphate-buffered saline.
KRYSTEXXA (pegloticase) concentrations are expressed as concentrations of uricase protein. Each mL of KRYSTEXXA contains 8mg of uricase protein (conjugated to 24mg of 10kDa mPEG), 2.18mg Disodium Hydrogen Phosphate Dihydrate (Na2HPO4•2H2O), 8.77mg Sodium Chloride (NaCl), 0.43mg Sodium Dihydrogen Phosphate Dihydrate (NaH2PO4&bull |
