Version May 2024
Patients treated with pegunigalsidase alfa have experienced hypersensitivity reactions, including anaphylaxis. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during pegunigalsidase alfa administration. If a severe hypersensitivity reaction (eg, anaphylaxis) occurs, discontinue pegunigalsidase alfa immediately and initiate appropriate medical treatment. In patients with severe hypersensitivity reaction, a desensitization procedure to pegunigalsidase alfa may be considered.
Note: Consider premedication with an antipyretic (eg, acetaminophen), antihistamines (eg, diphenhydramine), and/or corticosteroids (eg, prednisone) in patients who are enzyme replacement therapy (ERT)–naive or who are ERT-experienced but previously required pretreatment medications. After 4 to 6 infusions, a stepwise decrease in pretreatment medication dose(s) and/or discontinuation of pretreatment medication(s) may be considered in patients tolerating treatment.
Fabry disease: IV: 1 mg/kg every 2 weeks.
Missed doses : If ≥1 dose is missed, administer the missed dose as soon as possible and restart the 2-week interval.
There are no dosage adjustments provided in the manufacturer's labeling.
Kidney toxicity during treatment:
Membranoproliferative glomerulonephritis: Discontinue pegunigalsidase alfa.
There are no dosage adjustments provided in the manufacturer's labeling.
Hypersensitivity or infusion reaction, mild to moderate: Consider temporarily holding infusion for 15 to 30 minutes or slowing the infusion rate by 25% to 50%; institute appropriate medical treatment.
If symptoms persist after initially holding or slowing infusion rate: Discontinue the infusion and monitor the patient; consider reinitiating the infusion within 7 to 14 days at 25% to 50% of the rate at which the reaction occurred with appropriate pretreatment.
If symptoms subside after initially holding the infusion: Resume infusion at a 25% to 50% reduced rate as tolerated. Starting with the next infusion, increase the infusion rate in increments of 25% every third infusion as tolerated until the infusion rate at which the reaction occurred is reached; monitor closely.
If symptoms subside after initially reducing the infusion rate: Complete infusion at the reduced rate as tolerated. Starting with the next infusion, increase the infusion rate in increments of 25% every third infusion as tolerated until the infusion rate at which the reaction occurred is reached; monitor closely.
Hypersensitivity (eg, anaphylaxis) or infusion reaction, severe: Immediately discontinue pegunigalsidase alfa and institute appropriate medical treatment. Consider the risks and benefits of readministering pegunigalsidase alfa; patients may be rechallenged using slower infusion rates or desensitization measures.
Refer to adult dosing.
Type 1 hypersensitivity reaction, including anaphylaxis and severe hypersensitivity reaction, have been reported with pegunigalsidase alfa. Signs and symptoms of hypersensitivity included airway obstruction, angioedema, bronchospasm, headache, hypotension, macroglossia, nausea, pruritus, rash, rigors, tachycardia, throat tightness, urticaria, and vomiting.
Mechanism: Non–dose-related; immediate allergic hypersensitivity reactions (eg, anaphylaxis) are typically IgE mediated; delayed-type reactions may be T-cell mediated or antibodies other than IgE (eg, IgG mediated) (Ref)
Onset: Rapid; anaphylaxis occurred within 5 to 40 minutes after infusion initiation; other hypersensitivity reactions including rash and face swelling may occur up to 24 hours after infusion completion.
Risk factors:
• Preexisting anti-drug antibodies from prior enzyme replacement therapy
• Anti–pegunigalsidase alfa-iwxj IgE antibodies
• Higher infusion rates
Infusion-related reaction (IRR) has been reported with pegunigalsidase alfa. Most IRRs were mild to moderate, although serious reactions were also reported (Ref).
Onset: Rapid; has been reported after the start of the infusion and extending up to 24 hours after completion of infusion.
Risk factors:
• IgG or IgE anti-drug antibodies (Ref)
• Preexisting anti-drug antibodies from prior enzyme replacement therapy
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in enzyme replacement therapy (ERT)-experienced adults.
>10%:
Gastrointestinal: Abdominal pain (12%), diarrhea (19%), nausea (17%)
Genitourinary: Proteinuria (12%)
Hypersensitivity: Hypersensitivity reaction (9% to 14%; including anaphylaxis and severe hypersensitivity reaction) (table 1), infusion-related reaction (29% to 32%) (table 2)
|
Drug (Pegunigalsidase Alfa) |
Comparator (Agalsidase Beta) |
Number of Patients (Pegunigalsidase Alfa) |
Number of Patients (Agalsidase Beta) |
|---|---|---|---|
|
14% |
N/A |
N/A |
N/A |
|
9% |
16% |
52 |
32 |
|
Drug (Pegunigalsidase Alfa) |
Comparator (Agalsidase Beta) |
Number of Patients (Pegunigalsidase Alfa) |
Number of Patients (Agalsidase Beta) |
|---|---|---|---|
|
32% |
32% |
52 |
32 |
|
29% |
N/A |
N/A |
N/A |
Immunologic: Antibody development (females: 13% [neutralizing: 4%]; males: 59% [neutralizing: 48%])
Nervous system: Fatigue (17%), headache (21%)
Neuromuscular & skeletal: Back pain (15%), limb pain (15%)
Respiratory: Nasopharyngitis (21%), sinusitis (15%)
1% to 10%:
Genitourinary: Hematuria (6%)
Nervous system: Neuralgia (8%), peripheral neuropathy (6%), sciatica (6%)
Renal: Membranoproliferative glomerulonephritis (2%)
Respiratory: Respiratory congestion (upper respiratory tract: 8%)
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Antibody formation: The development of IgG anti-drug antibodies may occur and has been observed within 26 weeks from the onset of therapy. Patients who have received prior enzyme replacement therapy are more likely to have preexisting anti-drug antibodies, which may reduce pegunigalsidase alfa efficacy and increase the risk for hypersensitivity and infusion-related reactions.
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis (occurring within 5 to 40 minutes of the initial infusion), have been reported with pegunigalsidase alfa use. Signs and symptoms of hypersensitivity have included airway obstruction, angioedema, bronchospasm, headache, hypotension, macroglossia, nausea, pruritus, rash, rigors, tachycardia, throat tightness, urticaria, and vomiting. Patients who develop IgE antibodies may be at a higher risk for hypersensitivity reactions. Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids.
• Infusion reactions: Infusion-related reactions (eg, abdominal pain, agitation, bradycardia, burning sensation, chest pain, chills, diarrhea, dizziness, dyspnea, erythema, fever, flushing, headache, hypertension, hypotension, myalgia, nasal congestion, nausea, neuralgia, pain, paresthesia, pruritus, rash, sneezing, throat irritation, tremor, weakness, vomiting) may occur at onset of infusion and up to 24 hours after the end of the infusion. Patients who develop IgG antibodies may be at a higher risk for infusion reactions. Reactions were usually managed with antipyretics, antihistamines, corticosteroids, IV fluids, and/or oxygen. Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids. Infusion reactions have occurred despite premedication.
• Membranoproliferative glomerulonephritis: Membranoproliferative glomerulonephritis with immune deposits in the kidney leading to decreased renal function has been reported. Renal function slowly improved upon discontinuation but did not return to baseline.
Disease-related concerns:
• Cardiovascular disease: Patients with advanced Fabry disease may have compromised cardiac function and be at increased risk of complications from infusion reactions.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Elfabrio: Pegunigalsidase alfa-iwxj 20 mg/10 mL (10 mL)
No
Solution (Elfabrio Intravenous)
20 mg/10 mL (per mL): $521.02
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: Infuse through a low protein-binding 0.2-micron in-line filter. See tables for initial infusion rates for the first 4 to 6 infusions. After the initial 4 to 6 infusions, the duration of every third infusion may be decreased in decrements of 30 minutes as tolerated; minimum infusion rate is 1.5 hours. After administration, flush infusion line with NS using the same infusion rate used for the last part of the pegunigalsidase infusion. Health care providers may consider home infusion in patients reaching an infusion duration that is well tolerated; infusion duration should remain constant and rate changes should only occur in a health care facility.
|
Patient weight (actual body weight) |
Infusion ratea,b |
|---|---|
|
a Infusion rate may be increased if the patient tolerates the initial 4 to 6 infusions or may be reduced if hypersensitivity or infusion reaction occurs. | |
|
b In patients previously treated with an enzyme replacement therapy infusion duration over 3 hours, use the same initial infusion rate for the pegunigalsidase infusion; may decrease duration of every third infusion in decrements of 30 minutes as tolerated. | |
|
<70 kg |
0.83 mL/minute |
|
70 to 100 kg |
1.39 mL/minute |
|
>100 kg |
2.78 mL/minute |
|
Patient weight (actual body weight) |
Infusion ratea |
|---|---|
|
a Infusion rate may be increased if the patient tolerates the initial 4 to 6 infusions or may be reduced if hypersensitivity or infusion reaction occurs. | |
|
<70 kg |
0.63 mL/minute |
|
70 to 100 kg |
1 mL/minute |
|
>100 kg |
1.38 mL/minute |
Fabry disease: Enzyme replacement therapy for adults with confirmed Fabry disease (Anderson-Fabry disease).
Pegunigalsidase alfa may be confused with pegaspargase or pegloticase.
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.
Pegloticase: May diminish the therapeutic effect of PEGylated Drug Products. Risk C: Monitor therapy
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
Adverse events were not observed in reproduction studies conducted in rats using doses 3.6 times the recommended human dose; maternal toxicity was observed in rabbit studies using doses 6.5 times the recommended dose. Adverse events in humans would not be expected when used for enzyme replacement therapy.
Data collection to monitor pregnancy and infant outcomes following exposure to pegunigalsidase alfa is ongoing. Health care providers are encouraged to enroll patients exposed to pegunigalsidase alfa during pregnancy in the safety study (1-888-661-9260 or https://chiesirarediseases.com/contact-us/medicalinformation-form).
It is not known if pegunigalsidase alfa is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Serum creatinine and urinary protein to creatinine ratio; signs and symptoms of hypersensitivity and infusion reactions (especially in patients with compromised cardiac function); presence of IgG and IgE anti-pegunigalsidase alfa antibodies in patients developing hypersensitivity or infusion reactions.
Pegunigalsidase alfa is a recombinant form of the enzyme alpha-galactosidase-A, which catalyzes the hydrolysis of globotriaosylceramide (Gb-3), cleaving a terminal galactose residue from the molecule. Accumulation of globotriaosylceramide (Gb-3) may occur within the tissues of patients with Fabry disease. Pegunigalsidase alfa is internalized and transported into lysosomes exerting enzymatic activity and reducing cellular levels of Gb-3.
Distribution: Vdss: Mean range: 95 to 392 mL/kg.
Half-life elimination: Mean range: 57.3 to 143 hours.
Excretion: Clearance: Mean range: 1 to 3.6 mL/hour/kg.
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