Version May 2024
Anaphylaxis and infusion reactions have been reported to occur during and after administration of pegloticase. Anaphylaxis may occur with any infusion, and generally manifests within 2 hours of the infusion. However, delayed hypersensitivity reactions have also been reported. Pegloticase should be administered in health care settings by health care 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 pegloticase. 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 pegloticase. Hemolysis and methemoglobinemia have been reported with pegloticase in patients with G6PD deficiency. Pegloticase is contraindicated in patients with G6PD deficiency.
Note: Discontinue use of oral antihyperuricemic agents prior to initiating pegloticase and do not initiate during the course of therapy. Premedicate with antihistamines and corticosteroids. Gout flare prophylaxis with either NSAIDs or colchicine is also recommended, beginning at least 1 week prior to initiation and continuing for at least 6 months. Obtain serum uric acid levels prior to each infusion.
Gout: IV: 8 mg every 2 weeks as monotherapy (if methotrexate is contraindicated or not clinically appropriate), or coadministered with weekly oral methotrexate and folic acid or folinic acid supplementation; begin methotrexate and folic acid/folinic acid at least 4 weeks prior to starting pegloticase. Note: Discontinue pegloticase if preinfusion serum uric acid levels initially decrease but subsequent preinfusion levels rebound to >6 mg/dL, especially if 2 consecutive levels of >6 mg/dL are observed.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Dermatologic: Ecchymoses (≤11%)
Endocrine & metabolic: Acute gout attack (within the first 3 months: 74%; within 4 to 6 months: 41%)
Gastrointestinal: Nausea (12%)
Hematologic & oncologic: Bruise (≤11%)
Hypersensitivity: Infusion-related reaction (26%)
Immunologic: Antibody development (antipegloticase antibodies: 92%; anti-PEG antibodies: 42%)
1% to 10%:
Cardiovascular: Chest pain (6%), exacerbation of congestive heart failure (2%)
Gastrointestinal: Constipation (6%), vomiting (5%)
Hypersensitivity: Anaphylaxis (5% to 7%)
Respiratory: Nasopharyngitis (7%)
Postmarketing:
Cardiovascular: Peripheral edema
Hypersensitivity: Type IV hypersensitivity reaction
Nervous system: Asthenia, malaise
History of serious hypersensitivity, including anaphylaxis, to pegloticase or any component of the formulation; G6PD deficiency.
Concerns related to adverse effects:
• Hypersensitivity/anaphylactoid reactions: Anaphylaxis and infusion reactions have been reported during and after administration. Infusion reactions are varied; symptoms range from chest pain, pruritus/urticaria, erythema, or dyspnea to a clinical presentation of anaphylaxis (eg, hemodynamic instability, perioral or lingual edema). If a less severe (nonanaphylactic) infusion reaction occurs, the infusion may be slowed, or stopped and restarted at a slower rate, at the physician's discretion. Risk of an infusion reaction is increased in patients whose uric acid is >6 mg/dL. Since oral antihyperuricemic agents may blunt the rise of serum uric acid levels, discontinue use prior to and do not initiate during the course of pegloticase therapy.
• Gout flares: Therapy with antihyperuricemic agents commonly results in gout flare, particularly upon initiation due to rapid lowering of urate concentrations; gout flare-ups during treatment do not warrant discontinuation of therapy. Gout flare prophylaxis is recommended, using nonsteroidal anti-inflammatory agents (NSAID) or colchicine, unless contraindicated, beginning ≥1 week before initiation of pegloticase and continuing for at least 6 months.
Disease-related concerns:
• Heart failure: Exacerbation of heart failure has been observed in clinical trials; use caution in patients with preexisting heart failure.
• G6PD deficiency: Patients at increased risk for G6PD deficiency (eg, African, Mediterranean [including Southern European and Middle Eastern], and Southern Asian ancestry) should be screened prior to initiation of therapy.
Concurrent drug therapy issues:
• Oral antihyperuricemic agents: Use with oral antihyperuricemic agents may delay interpretations of ineffective pegloticase treatment (ie, serum uric acid >6 mg/dL) and ultimately increase risk for anaphylactoid and/or infusion reactions. Discontinue use of oral antihyperuricemic agents prior to and do not initiate during the course of pegloticase therapy.
Other warnings/precautions:
• Immunogenicity: Potential for immunogenicity exists with the use of therapeutic proteins. Antipegloticase antibodies and antiPEG antibodies commonly occurred during clinical trials in pegloticase-treated patients. High antipegloticase antibody titers were associated with failure to maintain uric acid normalization and were also associated with a higher incidence of infusion reactions. Due to potential for immunogenicity, closely monitor patients who reinitiate therapy after discontinuing treatment for >4 weeks; patients may be at increased risk for anaphylaxis and infusion reactions.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Krystexxa: 8 mg/mL (1 mL)
No
Solution (Krystexxa Intravenous)
8 mg/mL (per mL): $33,552.67
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
IV: Administer diluted solution by IV infusion over ≥120 minutes via gravity feed or an infusion pump or syringe-type pump. Do not administer by IV push or bolus. Administer in a healthcare setting by healthcare providers prepared to manage potential anaphylaxis. Monitor closely for infusion reactions during infusion and for an appropriate period of time after the infusion (manufacturer recommends for ~1 hour). In the event of a less severe infusion reaction, infusion may be slowed, or stopped and restarted at a slower rate, based on the discretion of the physician.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125293s104lbl.pdf#page=18, must be dispensed with this medication.
Gout: Treatment of chronic gout in adults refractory to conventional therapy
Limitations of use: Not for the treatment of asymptomatic hyperuricemia
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Allopurinol: May enhance the adverse/toxic effect of Pegloticase. Specifically, Allopurinol may blunt increases in serum urate that would signal an increased risk of anaphylaxis and infusion reactions. Risk X: Avoid combination
Benzbromarone: May enhance the adverse/toxic effect of Pegloticase. Specifically, Benzbromarone may blunt increases in serum urate that would signal an increased risk of anaphylaxis and infusion reactions. Risk X: Avoid combination
Febuxostat: May enhance the adverse/toxic effect of Pegloticase. Specifically, Febuxostat may blunt increases in serum urate that would signal an elevated risk of anaphylaxis and infusion reactions. Risk X: Avoid combination
Pegvaliase: PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor therapy
PEGylated Drug Products: Pegloticase may diminish the therapeutic effect of PEGylated Drug Products. Risk C: Monitor therapy
Probenecid: May enhance the adverse/toxic effect of Pegloticase. Specifically, Probenecid may blunt increases in serum urate that would signal an elevated risk of anaphylaxis and infusion reactions. Risk X: Avoid combination
Sulfinpyrazone: May enhance the adverse/toxic effect of Pegloticase. Specifically, Sulfinpyrazone may blunt increases in serum urate that would signal an increased risk of anaphylaxis and infusion reactions. Risk X: Avoid combination
Adverse events have been observed in some animal reproduction studies.
It is not known if pegloticase is present in breast milk. The manufacturer does not recommend breastfeeding unless the potential benefit to the mother is greater than the possible risk to the infant.
Serum uric acid levels at baseline and prior to infusions (beginning with the second infusion and preferably drawn 24 to 48 hours before the infusion to inform the impending dose [Keenan 2019]); consider discontinuation if preinfusion levels initially decrease but subsequent preinfusion levels rebound to >6 mg/dL, especially if 2 consecutive levels of >6 mg/dL are observed. Monitor for infusion reactions and anaphylaxis (during infusion and for ~1 hour postinfusion); due to potential for immunogenicity, closely monitor patients who reinitiate therapy after discontinuing treatment for >4 weeks; patients may be at increased risk for anaphylaxis and infusion reactions. Perform G6PD deficiency screening (in patients at high risk for deficiency).
Uric acid, serum:
Adults:
Normal values:
Males: 3.4 to 7 mg/dL or slightly more
Females: 2.4 to 6 mg/dL or slightly more
Goal during therapy: <6 mg/dL; <5 mg/dL in patients with severe gout (eg, tophi, frequent attacks, chronic arthropathy) (EULAR [Richette 2017]). Levels <3 mg/dL are not recommended long-term (EULAR [Richette 2017]).
Note: Serum uric acid values >7 mg/dL do not necessarily represent clinical gout; the American College of Rheumatology clinical practice guidelines recommend against initiating pharmacologic management of asymptomatic hyperuricemia (ACR [FitzGerald 2020]).
Pegloticase is a pegylated recombinant form of urate-oxidase enzyme, also known as uricase (an enzyme normally absent in humans and high primates), which converts uric acid to allantoin (an inactive and water soluble metabolite of uric acid); it does not inhibit the formation of uric acid.
Onset of action: ~24 hours following the first dose, serum uric acid concentrations decreased
Duration: >300 hours (12.5 days)
Half-life elimination: Median: ~14 days
Excretion: Urine (as allantoin)
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