Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 2mg/mL (20mg/10mL single-dose vial)
Fabry Disease
Indicated for adults with confirmed Fabry disease
1 mg/kg IV q2weeks
Use actual body weight to calculate dose
Pretreatment
-
Enzyme replacement therapy (ERT)-experienced patients
- If pretreatment with antihistamines, antipyretics, and/or corticosteroids was used before administering ERT, consider similar pretreatment with these medications before first several pegunigalsidase infusions
- If tolerated after 4-6 infusions, consider a stepwise decrease in pretreatment medication dose(s) and/or discontinuing
-
ERT-naïve patients
- Consider administering antihistamines, antipyretics, and/or corticosteroids before pegunigalsidase alfa infusion
Dosage Modifications
Hypersensitivity and/or infusion-associated reactions (IAR)
-
Mild-to-moderate
- Consider temporarily holding infusion for 15-30 minutes or slowing infusion rate by 25-50%, and initiating appropriate medical treatment
- If symptoms persist despite holding or slowing infusion, stop infusion and monitor; consider reinitiating within 7-14 days with infusion rate decreased by 25-50%
- If symptoms subside after holding infusion, resume and decrease infusion rate by 25-50% as tolerated
- Starting with next infusion, increase infusion rate by increments of 25% every third infusion as tolerated until infusion rate at which the reaction occurred is reached, and closely monitor
-
Severe
- Immediately discontinue infusion and initiate appropriate medical treatment
Renal or hepatic impairment
- No recommendations are provided in the prescribing information
Safety and efficacy not established
Adverse Effects
>10%
Infusion-associated reaction (32%)
Nasopharyngitis (21%)
Headache (21%)
Diarrhea (19%)
Fatigue (17%)
Nausea (17%)
Back pain (15%)
Pain in extremity (15%)
Sinusitis (15%)
Abdominal pain (12%)
Proteinuria (12%)
1-10%
Hypersensitivity (9%)
Upper respiratory tract congestion (8%)
Neuralgia (8%)
Peripheral neuropathy (6%)
Sciatica (6%)
Infusion site extravasation (6%)
Hematuria (6%)
Frequency Not Defined
Membranoproliferative glomerulonephritis in 1 patient
Warnings
Black Box Warnings
Hypersensitivity reactions, including anaphylaxis, reported
Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during administration
If a severe hypersensitivity reaction (eg, anaphylaxis) occurs, discontinue immediately and initiate appropriate medical treatment
In patients with severe hypersensitivity reaction, a desensitization procedure to may be considered
Contraindications
None
Cautions
Hypersensitivity
- Hypersensitivity reactions, including anaphylaxis, reported
- Consider pretreating with antihistamines, antipyretics, and/or corticosteroids
- Risk of hypersensitivity may be increased in certain patients with pre-existing anti-drug antibodies (ADA) from prior ERT; consider monitoring patients who demonstrate hypersensitivity reactions during treatment for presence of IgG and IgE ADA
- Also, see Boxed Warning and Dosage Modifications
Infusion-associated reactions (IARs)
- IARs reported, including nausea, chills, pruritus, rash, chest pain, dizziness, vomiting, asthenia, pain, sneezing, dyspnea, nasal congestion, throat irritation, abdominal pain, erythema, diarrhea, burning sensation, neuralgia, headache, paresthesia, tremor, agitation, increased body temperature, flushing, bradycardia, myalgia, hypertension, and hypotension
- Reactions may occur up to 24 hr after completing infusion
- Consider pretreating with antihistamines, antipyretics, and/or corticosteroids
- Risk of hypersensitivity may be increased in certain patients with pre-existing anti-drug antibodies (ADA) from prior ERT; consider monitoring
- Patients with advanced Fabry disease may have compromised cardiac function which, may predispose them to higher risk of severe complications from IARs; closely monitor patients with compromised cardiac function if administered to these patients
- Also, see Dosage Modifications
Membranoproliferative glomerulonephritis
- A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported during clinical trials
- This event led to a decline in renal function that slowly improved upon discontinuation but did not return to baseline by the end of the clinical trial
- Monitor serum creatinine and urinary protein to creatinine ratio
- If glomerulonephritis is suspected, discontinue pegunigalsidase alfa until a diagnostic evaluation can be conducted
Pregnancy & Lactation
Pregnancy
There are no available data regarding use in pregnant females to evaluate a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
As an enzyme replacement, pegunigalsidase alfa is not expected to cause adverse outcomes during pregnancy
Pregnancy safety study
- There is a pregnancy safety study for pegunigalsidase alfa
- If a patient becomes pregnant during treatment, report exposure by calling 1-888-661-9260 or visiting chiesirarediseases.com/contact-us/medical-information-form
Animal studies
- No adverse effects on embryofetal development were observed in pregnant rats administered pegunigalsidase alfa IV twice per week at exposures up to 3.6 times the maximum recommended human dose (MRHD)
- Maternal toxicity was observed in pregnant rabbits administered pegunigalsidase alfa IV twice per week at doses that were ≥3.2 times the MRHD (based on human equivalent dose)
Lactation
Data are unavailable on presence in either human or animal milk, effects on breastfed infants, or effects on milk production
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Fabry disease is caused by deficiency of the lysosomal enzyme alpha-galactosidase A involved in the metabolism of globotriaosylceramide (GL-3)
Pegunigalsidase alfa is an exogenous source of alpha-galactosidase A
Pegunigalsidase alfa is internalized and transported into lysosomes where it is thought to exert enzymatic activity and reduce accumulated Gb3 and reduce GL-3 deposition in capillary endothelium, and thereby, improving associated clinical manifestations (eg, vascular occlusion, stroke, renal failure, heart failure)
Absorption
Peak plasma concentration
- Day 1: 11.1 mcg/mL
- Week 13: 11.9 mcg/mL
- Week 26: 13.3 mcg/mL
- Week 52: 17.3 mcg/mL
AUC
- Day 1: 391 mcgh/mL
- Week 13: 510 mcgh/mL
- Week 26: 748 mcgh/mL
- Week 52: 1428 mcgh/mL
Distribution
Vd
- Day 1: 321 mL/kg
- Week 13: 271 mL/kg
- Week 26: 226 mL/kg
- Week 52: 186 mL/kg
Metabolism
Expected metabolism into small peptides by catabolic pathways
Elimination
Half-life
- Day 1: 78.9 hr
- Week 13: 85.7 hr
- Week 26: 96.5 hr
- Week 52: 121 hr
Clearance
- Day 1: 2.9 mL/hr/kg
- Week 13: 2.3 mL/hr/kg
- Week 26: 1.6 mL/hr/kg
- Week 52: 1.1 mL/hr/kg
Administration
IV Compatibilities
0.9% NaCl
IV Preparation
Determine number of pegunigalsidase alfa vials to be diluted based on actual body weight in kg and the recommended dose
Round number of vials up to next whole number
Remove vials from refrigerator and allow to sit for 15-30 minutes at room temperature before use; do not use an external heat source to heat product (heat may damage product)
Visually inspect solution for particulate matter and discoloration
Solution should be clear and colorless; discard vial(s) if solution discolored or if visible particulate matter is present
Further dilution required
- Dilute solution required for dose in 0.9% NaCl to a total volume based on actual body weight
-
Total volume of dilution and body weight
- <70 kg: 150 mL
- 70-100 kg: 250 mL
- >100 kg: 500 mL
- Before adding volume of pegunigalsidase alfa dose, remove equal volume of 0.9% NaCl from infusion bag
- Withdraw dose from vials and inject solution directly into 0.9% NaCl through infusion bag port; do not inject in the airspace within the infusion bag
- Discard any unused solution remaining in vial(s)
- Gently invert infusion bag to mix; avoid vigorous shaking or agitation
IV Administration
Administer pretreatment regimen if applicable
Appropriate medical support measures including cardiopulmonary resuscitation equipment should be readily available during administration
Use an in-line low protein-binding, 0.2 micron, in-line filter
At end of infusion, flush line with 0.9% NaCl using same infusion rate at completion of infusion
Do not infuse in same IV line with other products
If initial 4-6 infusions tolerated, duration of every third infusion may be decreased in decrements of 30 minutes as tolerated; minimum recommended infusion duration is 1.5 hr
Infusion rate for initial 4-6 doses
- Base infusion rate on actual body weight
-
Enzyme replacement therapy (ERT)-experienced patients
- <70 kg: 150 mL total infusion volume at 0.83 mL/min (50 mL/hr)
- 70-100 kg: 250 mL total infusion volume at 1.39 mL/min (83 mL/hr)
- >100 kg: 500 mL total infusion volume at 2.78 mL/min 167 mL/hr)
-
Enzyme replacement therapy (ERT)-naïve patients
- <70 kg: 150 mL total infusion volume at 0.63 mL/min (37.5 mL/hr)
- 70-100 kg: 250 mL total infusion volume at 1 mL/min (60 mL/hr)
- >100 kg: 500 mL total infusion volume at 1.38 mL/min (83 mL/hr)
-
Previously treated with an ERT with infusion over 3 hours
- Use the same infusion rate for pegunigalsidase alfa infusion
- May decrease duration of every third infusion after the initial 4-6 infusions in decrements of 30 minutes as tolerated; minimum recommended infusion duration is 1.5 hr
Missed dose
- If ≥1 doses missed, restart treatment as soon as possible, maintaining the 2-week interval between infusions thereafter
- Do not double a dose to compensate for missed dose
Home infusion
- May consider for patients who have reached an infusion duration that is tolerated well
- Decision to move to home infusion based on evaluation and recommendation by a healthcare provider
- Infusion duration should remain constant for home administration and duration should only be decreased in a healthcare facility
- Contact clinician if dose is missed dose or delayed
Storage
Unopened vials
- Refrigerate at 2-8ºC (36-46ºF)
- Do not freeze
- Do not shake
Diluted solution
- Refrigerate at 2-8ºC (36-46ºF) for up to 24 hr, OR
- Store at room temperature of 20-25ºC (68-77ºF) for up to 8 hr
- Solution must be infused within 8 hr after removal from refrigerator or if stored at room temperature, inclusive of total infusion time, or discarded
- Do not freeze
- Do not shake
Images
Formulary
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