onasemnogene abeparvovec (Rx)

Brand and Other Names:Zolgensma, onasemnogene abeparvovec-xioi
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Dosing & Uses

AdultPediatric

See Pediatric Dosing

Dosage Forms & Strengths

suspension for IV infusion

  • Provided in a kit containing 2 to 9 vials, as a combination of 2 vial fill volumes (either 5.5 mL or 8.3 mL)
  • All vials have a nominal concentration of 2 x 10^13 vector genomes (vg) per mL
  • Each vial contains an extractable volume of not less than either 5.5 mL or 8.3 mL

Spinal Muscular Atrophy Type 1

Indicated for gene replacement therapy in children aged <2 years with spinal muscular atrophy (SMA) type 1 (also called Werdnig-Hoffman disease) who have biallelic mutation in the survival motor neuron 1 (SNM1) gene

≥2 years: Safety and efficacy not established

Administered as a one-time, single IV infusion through a venous catheter

1.1 x 10^14 vector genomes per kilogram (vg/kg) of body weight

Dose calculation

  • See prescribing information for weight-range dosing chart
  • Age <2 yr weighing 2.6-13.5 kg: Dose volume calculated using upper limit of patient weight range
  • Age <2 yr weighing ≥13.6 kg: Dose volume will require a combination of onasemnogene abeparvovec kits

Prior to infusion

  • Assess liver function
  • Measure platelet counts and troponin-I
  • Perform baseline testing for presence of anti-AAV9 antibodies
  • 1 day before infusion: Begin systemic corticosteroids equivalent to oral prednisolone 1 mg/kg/day for a total of 30 days

Dosing Considerations

Limitations of use

  • Safety and effectiveness of repeat administration has not been evaluated
  • Use for advanced SMA (eg, complete paralysis of limbs, permanent ventilator-dependence) has not been evaluated
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Interactions

Interaction Checker

and onasemnogene abeparvovec

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    Contraindicated

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            Adverse Effects

            >10%

            Elevated aminotransferases (>ULN) (27.3%)

            1-10%

            Vomiting (6.8%)

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            Warnings

            Black Box Warnings

            Acute serious liver injury and elevated aminotransferases can occur

            Patients with pre-existing liver impairment may be at higher risk

            Prior to infusion, assess liver function of all patients by clinical examination and laboratory testing (eg, AST, ALT, total bilirubin, prothrombin time)

            Administer systemic corticosteroid to all patients before and after onasemnogene abeparvovec infusion

            Continue monitoring liver function for at least 3 months after infusion

            Contraindications

            None

            Cautions

            Acute serious liver injury can occur; before infusion, assess liver function; continue monitoring liver function for at least 3 months after onasemnogene abeparvovec infusion; manage elevated aminotransferase with corticosteroids

            Transient decreases in platelet counts, some meeting criteria for thrombocytopenia, observed after infusion; monitor platelet counts before infusion and regularly afterwards (weekly for first month; q2wk for next 2 months)

            Transient increases in cardiac troponin-I levels observed after infusion; clinical importance of these findings are unknown; cardiac toxicity observed in animal studies; monitor troponin-I before infusion and then for at least 3 months afterwards (weekly for first month; q2wk for next 2 months)

            Drug interaction overview

            • Where feasible, adjust vaccination schedule to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion
            • Certain vaccines (eg, MMR, varicella) are contraindicated for patients on a substantially immunosuppressive steroid dose (ie, ≥2 weeks of prednisone 2 mg/kg/day or 20 mg/day or equivalent)
            • Seasonal RSV prophylaxis is not precluded
            • Refer to CDC vaccination guidelines for immunosuppressed patients
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            Pregnancy

            Pregnancy

            There are no data regarding use in pregnant women

            No animal reproductive studies conducted

            Lactation

            Unknown if secreted in human milk

            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.

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            Pharmacology

            Mechanism of Action

            Recombinant AAV9-based gene therapy designed to deliver a copy of the gene encoding the human survival motor neuron (SMN) protein

            Spinal muscular atrophy is caused by a bi-allelic mutation in the SMN1 gene, which results in insufficient SMN protein expression

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            Administration

            IV Preparation

            Thaw before use; contents of kit will thaw in ~12 hr if refrigerator or ~4 hr if at room temperature

            If thawed in refrigerator, remove from refrigerator on day of dosing

            When thawed, should appear clear to slightly opaque, colorless to faint white liquid, free of particles

            Visually inspect vials for particulate matter and discoloration before infusion

            Do not use vials if particulates or discoloration are present

            Do NOT shake

            Draw the appropriate dose volume from all vials into a syringe, remove air from the syringe, cap the syringe, and deliver the syringe at room temperature to the patient infusion location

            Use within 8 hr of drawing into syringe

            Discard the vector-containing syringe if the drug is not infused within the 8-hr time frame

            IV Administration

            For single-dose slow IV infusion only; do NOT infuse as an IV push or bolus

            Place primary catheter into vein (generally a peripheral vein in the arm or leg)

            Insertion of a back-up catheter is recommended

            Program syringe pump for saline priming, or prime tubing manually with saline

            Administer as a slow IV infusion over 60 minutes

            Flush line with saline following completion of infusion

            Storage

            Product is shipped and delivered frozen (≤ -60°C [-76°F]) in clear vials

            Upon receipt, immediately place the kit in refrigerator at 2-8°°C (36-46F)

            Stable for 14 days from receipt when stored refrigerated as directed

            Do NOT refreeze

            Must use within 14 days of receipt

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            Formulary

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.