Version May 2024
Cases of acute liver failure with fatal outcomes have been reported. Acute serious liver injury and elevated aminotransferases can occur with onasemnogene abeparvovec. Patients with preexisting liver impairment may be at higher risk. Prior to infusion, assess liver function of all patients by clinical examination and laboratory testing. Administer systemic corticosteroid to all patients before and after onasemnogene abeparvovec infusion. Continue to monitor liver function for at least 3 months after infusion and at other times as clinically indicated.
(For additional information see "Onasemnogene abeparvovec: Pediatric drug information")
Spinal muscular atrophy (SMA):
Note: Patients should be clinically stable in overall baseline health status (eg, hydration and nutritional status, absence of infection [including no signs or symptoms of infection]) prior to administration due to increased risk of systemic immune responses. Postpone therapy until resolution of any infection. One day prior to infusion, administer oral corticosteroids ( prednisolone 1 mg/kg/day or equivalent) and continue for ≥30 days; may use IV corticosteroids if oral therapy not tolerated. Evaluate baseline labs (SCr, CBC [platelets, Hb]), troponin-I, for presence of anti-AAV9 antibodies, and assess liver function.
Infants and Children <2 years: IV infusion: 1.1 × 1014 vector genomes/kg as a single dose.
Dose volume based on weight range:
|
Weight range (kg) |
Dose Volume (mL) |
|---|---|
|
2.6 to 3 kg |
16.5 mL |
|
3.1 to 3.5 kg |
19.3 mL |
|
3.6 to 4 kg |
22 mL |
|
4.1 to 4.5 kg |
24.8 mL |
|
4.6 to 5 kg |
27.5 mL |
|
5.1 to 5.5 kg |
30.3 mL |
|
5.6 to 6 kg |
33 mL |
|
6.1 to 6.5 kg |
35.8 mL |
|
6.6 to 7 kg |
38.5 mL |
|
7.1 to 7.5 kg |
41.3 mL |
|
7.6 to 8 kg |
44 mL |
|
8.1 to 8.5 kg |
46.8 mL |
|
8.6 to 9 kg |
49.5 mL |
|
9.1 to 9.5 kg |
52.3 mL |
|
9.6 to 10 kg |
55 mL |
|
10.1 to 10.5 kg |
57.8 mL |
|
10.6 to 11 kg |
60.5 mL |
|
11.1 to 11.5 kg |
63.3 mL |
|
11.6 to 12 kg |
66 mL |
|
12.1 to 12.5 kg |
68.8 mL |
|
12.6 to 13 kg |
71.5 mL |
|
13.1 to 13.5 kg |
74.3 mL |
|
13.6 to 14 kg |
77 mL |
|
14.1 to 14.5 kg |
79.8 mL |
|
14.6 to 15 kg |
82.5 mL |
|
15.1 to 15.5 kg |
85.3 mL |
|
15.6 to 16 kg |
88 mL |
|
16.1 to 16.5 kg |
90.8 mL |
|
16.6 to 17 kg |
93.5 mL |
|
17.1 to 17.5 kg |
96.3 mL |
|
17.6 to 18 kg |
99 mL |
|
18.1 to 18.5 kg |
101.8 mL |
|
18.6 to 19 kg |
104.5 mL |
|
19.1 to 19.5 kg |
107.3 mL |
|
19.6 to 20 kg |
110 mL |
|
20.1 to 20.5 kg |
112.8 mL |
|
20.6 to 21 kg |
115.5 mL |
Concomitant therapy: Beginning the day prior to onasemnogene abeparvovec infusion, oral corticosteroid (prednisolone 1 mg/kg/day or equivalent) should be administered and continued for ≥30 days to help prevent hepatic toxicity. At the end of 30 days, clinically assess liver status and check LFTs (ALT, AST, total bilirubin, PT, and INR) and manage as follows:
• If unremarkable findings (normal clinical exam, total bilirubin, PT, INR, and ALT and AST concentrations <2 × ULN), taper corticosteroid over 28 days; do not discontinue abruptly.
• If evidence of liver function abnormalities exists, continue oral corticosteroid (prednisolone 1 mg/kg/day or equivalent) until AST and ALT <2 × ULN and all other assessments return to normal, then taper corticosteroid over 28 days or longer if needed; do not discontinue abruptly.
• If liver function abnormalities persist ≥2 × ULN after 30 days of corticosteroid therapy, consult pediatric gastroenterologist or hepatologist.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling. Patients with preexisting hepatic impairment may be at increased risk for hepatotoxicity; patients with ALT, AST, or total bilirubin >2 × ULN were not included in clinical trials (this excludes neonatal jaundice); assess risk versus benefit. Acute liver injury may occur after therapy and may require prolonged corticosteroid therapy (see "Dosing: Pediatric"). Monitor liver function closely (clinical exams, AST, ALT, total bilirubin, PT, and INR).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in neonates, infants, and young children.
>10%:
Hepatic: Increased serum alanine aminotransferase (≤27%), increased serum aspartate aminotransferase (≤27%)
Immunologic: Antibody development (100%)
1% to 10%: Gastrointestinal: Vomiting (7%)
Postmarketing:
Cardiovascular: Troponin increased in blood specimen
Hematologic & oncologic: Thrombocytopenia, thrombotic microangiopathy (Chand 2021)
Hepatic: Acute hepatic failure, acute hepatotoxicity
Miscellaneous: Fever
There are no contraindications listed in the US manufacturer's labeling.
Canadian labeling: Hypersensitivity to onasemnogene abeparvovec or any component of the formulation.
Concerns related to adverse effects:
• Cardiac effects: Increases in troponin-I levels have been observed, but clinical significance is unknown; cardiac toxicity was observed in animal studies. Consider cardiology consult in patients with troponin elevations accompanied by cyanosis, heart rate changes, respiratory distress, or tachypnea.
• Hepatotoxicity: Acute serious liver injury and acute liver failure, including fatalities, as well as elevated transaminases have been reported and may be immune mediated in nature; concomitant systemic corticosteroids therapy should be continued for ≥28 days after dose. Patients with preexisting hepatic impairment or acute hepatic viral illness may be at increased risk for hepatotoxicity; use with caution.
• Thrombocytopenia: Transient decreases in platelet counts have been observed, typically within the first 2 weeks after the infusion.
• Thrombotic microangiopathy: Cases of thrombotic microangiopathy (TMA), including acute kidney injury, microangiopathic hemolytic anemia, and thrombocytopenia, have been reported within the first 2 weeks after therapy; may be life-threatening or fatal. Concurrent immune system activation (eg, infections, vaccinations) was present in some cases. Monitor patients closely and further evaluate patients for hemolytic anemia and renal impairment if signs occur in the presence of thrombocytopenia. Consult a pediatric hematologist and/or nephrologist immediately if clinical symptoms or laboratory findings are consistent with TMA.
Disease related concerns:
• Infection: Underlying active infection (acute or chronic) can lead to increased risk of serious systemic immune response, resulting in a more severe clinical course of the infection. Patients should be clinically stable in overall baseline health (eg, hydration and nutritional status, absence of infection) prior to infusion. Postpone therapy in patients with concurrent infection until the infection has resolved; risk of serious systemic immune response may occur.
Concurrent drug therapy issues:
• Vaccines: Vaccination schedule may need to be adjusted due to corticosteroid administration before and after onasemnogene abeparvovec infusion. Update seasonal influenza and respiratory syncytial virus vaccines prior to onasemnogene abeparvovec infusion.
Other warnings/precautions:
• Immunogenicity: Safety and efficacy have not been evaluated in patients with anti-AAV9 antibody titers above 1:50. Perform baseline testing for the presence of anti-AAV9 antibodies; retesting may be performed if anti-AAV9 antibody titers are reported as >1:50.
• Vector shedding: Temporary vector shedding of onasemnogene abeparvovec occurs primarily through body waste. Recommended procedures when handling patient feces include sealing disposable diapers in disposable trash bags and then discarding into regular trash. Use proper hand hygiene when coming into direct contact with patient body waste. Follow these precautions for 1 month after the infusion.
Administration to premature infants should be delayed until PMA is corrected to full term; concomitant use of corticosteroids may adversely affect neurological development.
Two cases of necrotizing enterocolitis (NEC) have been reported following onasemnogene administration in infants <2 months of age. In one report, hematochezia was initially observed 5 days post-infusion and 19 days post-infusion in the other case; causality has not been determined; monitor closely signs of NEC (eg, vomiting, hematochezia) (Gaillard 2023).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Injection [preservative free]:
Zolgensma: Onasemnogene abeparvovec-xioi 20000000000000 VG/mL (5.5 mL, 8.3 mL)
Kit (Zolgensma 20.6-21.0 kg Intravenous)
14x8.3 mL (per each): $0.00
Kit (Zolgensma 10.1-10.5 kg Intravenous)
7x8.3 mL (per each): $0.00
Kit (Zolgensma 10.6-11.0 kg Intravenous)
2x5.5ML &6x8.3ML (per each): $0.00
Kit (Zolgensma 11.1-11.5 kg Intravenous)
1x5.5ML &7x8.3ML (per each): $0.00
Kit (Zolgensma 11.6-12.0 kg Intravenous)
8x8.3 mL (per each): $0.00
Kit (Zolgensma 12.1-12.5 kg Intravenous)
2x5.5ML &7x8.3ML (per each): $0.00
Kit (Zolgensma 12.6-13.0 kg Intravenous)
1x5.5ML &8x8.3ML (per each): $0.00
Kit (Zolgensma 13.1-13.5 kg Intravenous)
9x8.3 mL (per each): $0.00
Kit (Zolgensma 13.6-14.0 kg Intravenous)
2x5.5ML &8x8.3ML (per each): $0.00
Kit (Zolgensma 14.1-14.5 kg Intravenous)
1x5.5ML &9x8.3ML (per each): $0.00
Kit (Zolgensma 14.6-15.0 kg Intravenous)
10x8.3 mL (per each): $0.00
Kit (Zolgensma 15.1-15.5 kg Intravenous)
2x5.5ML &9x8.3ML (per each): $0.00
Kit (Zolgensma 15.6-16.0 kg Intravenous)
1x5.5ML &10x8.3ML (per each): $0.00
Kit (Zolgensma 16.1-16.5 kg Intravenous)
11x8.3 mL (per each): $0.00
Kit (Zolgensma 16.6-17.0 kg Intravenous)
2x5.5ML &10x8.3ML (per each): $0.00
Kit (Zolgensma 17.1-17.5 kg Intravenous)
1x5.5ML &11x8.3ML (per each): $0.00
Kit (Zolgensma 17.6-18.0 kg Intravenous)
12x8.3 mL (per each): $0.00
Kit (Zolgensma 18.1-18.5 kg Intravenous)
2x5.5ML &11x8.3ML (per each): $0.00
Kit (Zolgensma 18.6-19.0 kg Intravenous)
1x5.5ML &12x8.3ML (per each): $0.00
Kit (Zolgensma 19.1-19.5 kg Intravenous)
13x8.3 mL (per each): $0.00
Kit (Zolgensma 19.6-20.0 kg Intravenous)
2x5.5ML &12x8.3ML (per each): $0.00
Kit (Zolgensma 2.6-3.0 kg Intravenous)
2x8.3 mL (per each): $0.00
Kit (Zolgensma 20.1-20.5 kg Intravenous)
1x5.5ML &13x8.3ML (per each): $0.00
Kit (Zolgensma 3.1-3.5 kg Intravenous)
2x5.5ML &1x8.3ML (per each): $0.00
Kit (Zolgensma 3.6-4.0 kg Intravenous)
1x5.5ML &2x8.3ML (per each): $0.00
Kit (Zolgensma 4.1-4.5 kg Intravenous)
3x8.3 mL (per each): $0.00
Kit (Zolgensma 4.6-5.0 kg Intravenous)
2x5.5ML &2x8.3ML (per each): $0.00
Kit (Zolgensma 5.1-5.5 kg Intravenous)
1x5.5ML &3x8.3ML (per each): $0.00
Kit (Zolgensma 5.6-6.0 kg Intravenous)
4x8.3 mL (per each): $0.00
Kit (Zolgensma 6.1-6.5 kg Intravenous)
2x5.5ML &3x8.3ML (per each): $0.00
Kit (Zolgensma 6.6-7.0 kg Intravenous)
1x5.5ML &4x8.3ML (per each): $0.00
Kit (Zolgensma 7.1-7.5 kg Intravenous)
5x8.3 mL (per each): $0.00
Kit (Zolgensma 7.6-8.0 kg Intravenous)
2x5.5ML &4x8.3ML (per each): $0.00
Kit (Zolgensma 8.1-8.5 kg Intravenous)
1x5.5ML &5x8.3ML (per each): $0.00
Kit (Zolgensma 8.6-9.0 kg Intravenous)
6x8.3 mL (per each): $0.00
Kit (Zolgensma 9.1-9.5 kg Intravenous)
2x5.5ML &5x8.3ML (per each): $0.00
Kit (Zolgensma 9.6-10.0 kg Intravenous)
1x5.5ML &6x8.3ML (per each): $0.00
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Injection:
Zolgensma: Onasemnogene abeparvovec-xioi 20000000000000 VG/mL (5.5 mL, 8.3 mL)
Parenteral: IV: For slow IV infusion only; do not administer as IV push or bolus. Flush with saline before and after administration. Infuse onasemnogene abeparvovec slowly over 60 minutes.
Spinal muscular atrophy: Treatment of pediatric patients <2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene
Limitations of use: Safety and effectiveness of repeat administration has not been evaluated. Use in patients with advanced SMA (eg, complete paralysis of limbs, permanent ventilator-dependence) has not been evaluated.
None known.
There are no known significant interactions.
Animal reproduction studies have not been conducted. Onasemnogene abeparvovec is not approved for use in patients of reproductive age.
It is not known if onasemnogene abeparvovec is present in breast milk.
It is not known if breastfeeding should be restricted in mothers who may be seropositive for anti-AAV9 antibodies. 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 benefits of treatment to the mother; however, onasemnogene abeparvovec is not approved for use in patients of reproductive age.
Baseline: Liver function (clinical exam, AST, ALT, total bilirubin, and PT), CBC (Hb, platelet count), SCr, troponin-I, and anti-AAV9 antibody test.
First month after treatment: Liver function (clinical exam, AST, ALT, total bilirubin, and PT), platelets, and troponin-I (check weekly); signs and symptoms of thrombotic microangiopathy (eg, hypertension, bruising, decreased urine output, seizures).
Second and third month after treatment: Liver function (clinical exam, AST, ALT, total bilirubin, and PT) every other week until AST/ALT are <2 × ULN, PT is normal, total bilirubin is normal, and clinical exam is normal; platelet count every other week until counts return to baseline, and troponin-I monthly until troponin-I level returns to baseline; signs and symptoms of thrombotic microangiopathy (eg, hypertension, bruising, decreased urine output, seizures).
A recombinant adeno-associated virus vector-based gene therapy that delivers a normal copy of the gene encoding human survival motor neuron (SMN) protein.
Following administration, generalized SMN expression was shown in spinal motor neurons, neuronal and glial cells of the brain, and in the heart, liver, skeletal muscles, and other tissues. Vector DNA can be detected in the spleen, heart, pancreas, inguinal lymph node, skeletal muscles, peripheral nerves, kidney, lung, intestines, spinal cord, brain, and thymus; the highest concentrations have been found in the liver. Vector DNA is shed in saliva, urine, and stool; undetectable levels here achieved within 3 weeks, 1 to 2 weeks, and 1 to 2 months, respectively, following infusion.
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