Dosage & Administration
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Krystexxa Prescribing Information
- Anaphylaxis and infusion reactions have been reported to occur during and after administration of KRYSTEXXA.
- Anaphylaxis may occur with any infusion, and generally manifests within 2 hours of the infusion. However, delayed hypersensitivity reactions have also been reported.
- KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions.
- Premedicate with antihistamines and corticosteroids and closely monitor for anaphylaxis for an appropriate period of time after administration of KRYSTEXXA.
- Monitor serum uric acid levels prior to each infusion and discontinue treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.
- Screen patients at risk for G6PD deficiency prior to starting KRYSTEXXA. Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. KRYSTEXXA is contraindicated in patients with G6PD deficiency.
KRYSTEXXA® (pegloticase) is indicated, for the treatment of chronic gout in adult patients refractory to conventional therapy.
Gout refractory to conventional therapy occurs in 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.
Limitations of Use:
KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia.
Important Administration Instructions
Precautions Prior to Treatment
It is recommended that before starting KRYSTEXXA patients discontinue oral urate-lowering medications and not institute therapy with oral urate-lowering agents while patients are on KRYSTEXXA therapy.
Monitoring Therapy: The risk of infusion reactions, including anaphylaxis, is higher in patients who have lost therapeutic response. Monitor serum uric acid levels prior to each infusion and discontinue treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed [see Warnings and Precautions (5.1, 5.2)].
Infusion Reaction Precautions
KRYSTEXXA should be administered in a healthcare setting by healthcare providers prepared to manage infusion reactions, including anaphylaxis. Observe patients for an appropriate period of time after administration [see Warnings and Precautions (5.1, 5.2)].
Patients should receive pre-infusion medications (e.g., antihistamines, corticosteroids), to minimize the risk of infusion reactions, including anaphylaxis.
If an infusion reaction occurs during the administration of KRYSTEXXA, the infusion may be slowed, or stopped and restarted at a slower rate, at the discretion of the physician. Since infusion reactions can occur after completion of infusion, observation of patients for approximately an hour post-infusion should be considered [see Warnings and Precautions (5.2), Adverse Reactions (6.1)].
Administration Precautions
KRYSTEXXA must be diluted prior to use. Do not administer KRYSTEXXA as an intravenous push or bolus. The KRYSTEXXA admixture should only be administered by intravenous infusion over no less than 120 minutes via gravity feed, syringe-type pump, or infusion pump.
Recommended Dosage and Administration
The recommended dosage is KRYSTEXXA 8 mg given as an intravenous infusion every two weeks, co-administered with weekly oral methotrexate 15 mg and folic acid or folinic acid supplementation. KRYSTEXXA alone may be used in patients for whom methotrexate is contraindicated or not clinically appropriate.
If co-administering with methotrexate, start weekly methotrexate and folic acid or folinic acid supplementation at least 4 weeks prior to initiating, and throughout treatment with KRYSTEXXA. [see Clinical Studies (14)]. Refer to the Full Prescribing Information for methotrexate.
The optimal treatment duration with KRYSTEXXA has not been established.
Preparation Instructions
Visually inspect KRYSTEXXA for particulate matter and discoloration before administration, whenever solution and container permit. Do not use vials if either is present.
Use appropriate aseptic technique. Withdraw 1 mL of KRYSTEXXA from the vial into a sterile syringe. Discard any unused portion of product remaining in the vial. Inject into a single 250 mL bag of 0.9% Sodium Chloride Injection, USP or 0.45% Sodium Chloride Injection, USP for intravenous infusion. Do not mix or dilute with other drugs.
Invert the infusion bag containing the dilute KRYSTEXXA solution a number of times to ensure thorough mixing. Do not shake.
KRYSTEXXA diluted in infusion bags is stable for 4 hours at 2ºC to 8ºC (36ºF to 46ºF) and at room temperature (20ºC to 25ºC, 68ºF to 77ºF). However, it is recommended that diluted solutions be stored under refrigeration, not frozen, protected from light, and used within 4 hours of dilution [see How Supplied/Storage and Handling (16)].
Before administration, allow the diluted solution of KRYSTEXXA to reach room temperature. KRYSTEXXA in a vial or in an intravenous infusion fluid should never be subjected to artificial heating (e.g., hot water, microwave).
Injection: 8 mg/mL as a clear and colorless solution for dilution in a single-dose vial. KRYSTEXXA concentrations are expressed as concentrations of uricase protein. Each mL of pegloticase contains 8 mg of uricase protein conjugated to monomethoxypoly (ethylene glycol) [mPEG].
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 by subcutaneous injection to pregnant rats and rabbits during the period of organogenesis at doses up to 50 and 75 times, respectively, the maximum recommended human dose (MRHD). Decreases in mean fetal and pup body weights were observed at approximately 50 and 75 times the MRHD, respectively [see Data].
All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinical recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
In 2 separate embryo-fetal developmental studies, pregnant rats and rabbits received pegloticase during the period of organogenesis at doses up to 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). No evidence of structural abnormalities was observed in rats or rabbits. However, decreases in mean fetal and pup body weights were observed at approximately 50 and 75 times the MRHD in rats and rabbits, 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).
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 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. In a 52-week, randomized, double-blind trial which evaluated KRYSTEXXA co-administered with methotrexate compared to KRYSTEXXA alone, 85% of patients had chronic kidney disease based on estimated glomerular filtration rate (eGFR) of ≥ 40 to < 90 mL/min/1.73m2 at baseline. In the pre-marketing 24-week controlled clinical trials with KRYSTEXXA alone, 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.
KRYSTEXXA is contraindicated in:
- Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency [see Warnings and Precautions (5.3)]
- Patients with history of serious hypersensitivity reactions, including anaphylaxis, to KRYSTEXXA or any of its components