Onasemnogene Abeparvovec Dosage

Medically reviewed by Drugs.com. Last updated on Mar 4, 2024.

Usual Pediatric Dose for Spinal Muscular Atrophy

Prior to infusion:

• Assess liver function by clinical examination and laboratory testing (ALT, AST, total bilirubin, and prothrombin time)
• Obtain creatinine, complete blood count (including hemoglobin and platelet counts), and troponin-I
• Assess for the presence of anti-AAV9 antibodies

Corticosteroid

• Initiate systemic corticosteroids 1 day prior to IV infusion and continue for a total of 30 days (equivalent to oral prednisolone 1 mg/kg/day)

Single-dose: 1.1 x 10(14) vector genomes/kg IV through a venous catheter over 60 minutes

Comments:

• See Other comments/Administration advice for guidance on administration; the manufacturer's product labeling provides a dose table which includes dose volume (mL) based on weight.
• The use in patients with advance spinal muscular atrophy (e.g., complete paralysis of limbs, permanent ventilator-dependence) has not been evaluated.
• The safety and effectiveness of repeat administration have not been evaluated.

Use: For the treatment of patients less than 2 years with spinal muscular atrophy with bi-allelic mutations in the survival motor neuron 1 gene; because concomitant treatment with corticosteroids may adversely affect neurological development, infusion should be delayed until corresponding full-term gestational age is reached.

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

Preexisting liver impairment: Use with caution as these patients may be at higher risk for liver injury; monitor liver function in all patients

Dose Adjustments

CORTICOSTEROID TREATMENT: Systemic corticosteroid therapy equivalent to oral prednisolone 1 mg/kg/day should be administered to all patients starting one day prior to therapy and continuing for a total of 30 days. At 30 days postdose:

• Patients with unremarkable findings (normal clinical exam, total bilirubin, and prothrombin time, and ALT and AST levels below 2 × upper limit of normal [2xULN]) should taper the corticosteroid dose over the next 28 days
• Patients with with liver function abnormalities should continue corticosteroids until AST and ALT values are both below 2 x ULN and all other assessments return to normal range and then the corticosteroid dose should be tapered over the next 28 days
• If liver function abnormalities persist, the patient should be referred to a specialist

Precautions

US BOXED WARNING: ACUTE SERIOUS LIVER INJURY

• Acute serious liver injury and elevated aminotransferases can occur with this drug; patients with preexisting liver impairment may be at higher risk.
• Prior to infusion, assess liver function by clinical examination and laboratory testing (e.g., hepatic transaminases [ALT, AST], total bilirubin, and prothrombin time).
• Administer systemic corticosteroid before and after infusion; continue to monitor liver function for at least 3 months after infusion.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in premature neonates before reaching full-term gestational age.

• Because concomitant treatment with corticosteroids may adversely affect neurological development, infusion should be delayed until corresponding full-term gestational age is reached.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• One day prior treatment initiation, start corticosteroid therapy (equivalent to oral prednisolone at 1 mg/kg/day); corticosteroid therapy will continue for at least 30 days; see dose adjustment section for further guidance
• Administer as a single dose IV infusion through a venous catheter over 60 minutes; do not administer as an IV push or bolus

Reconstitution/preparation techniques::

• Place a 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
• Thaw before use; contents in kit will thaw in approximately 12 hours in the refrigerator or 4 hours at room temperature; if thawed in refrigerator, remove from refrigerator on day of dosing
• Once thawed, suspension should be clear to slightly opaque (colorless to faint white); do not use if particulates or discoloration are present
• Do not shake
• Draw appropriate dose volume into syringe and deliver syringe at room temperature to infusion location; use within 8 hours; discard if not used within 8-hour timeframe; do not refreeze
• Following Infusion, flush line with saline

Storage requirements:

• Shipped frozen (-76F [-60C]); Upon receipt, immediately refrigerate 36F to 46F (2C to 8C)
• Stable for 14 days from receipt when stored refrigerated; Do not refreeze; must use within 14 days of receipt
• Once drawn up in syringe for administration, keep at room temperature and use within 8 hours

General:

• Alterations in vaccination schedule may be necessary during corticosteroid use; prophylaxis against respiratory syncytial virus is recommended.
• This drug should not be administered to premature neonates before reaching full-term gestational age as concomitant treatment with corticosteroids may adversely affect neurological development; delay infusion until the corresponding full-term gestational age is reached.

Monitoring:

• Assess liver function (clinical exam, AST, ALT, total bilirubin, prothrombin time) prior to therapy and weekly for the first month and every other week for the second and third months until results are unremarkable (normal clinical exam, total bilirubin, and prothrombin results, and ALT and AST levels below 2 × ULN)
• Obtain creatinine, complete blood count (including hemoglobin and platelet count) prior to therapy and monitor platelet counts weekly for the first month, and then every other week for the second and third months, until platelet counts return to baseline
• Obtain troponin-I levels prior to therapy and monitor troponin-I weekly for the first month, and then monthly for the second and third months, until troponin-I level returns to baseline
• Perform baseline testing for the presence of anti-AAV9 antibodies; may retest if anti-AAV9 antibody titers are reported as greater than 1:50

Patient advice:

• Caregivers should watch for and report any unexpected bruising or bleeding, seizures, or decreased urine output immediately, especially in the first week after therapy.
• Caregivers should understand that this drug may cause liver injury and they should report any signs of liver injury such as skin or whites of eyes appearing yellow.
• Caregivers should understand that steroid therapy is necessary to reduce the risk of liver injury and if doses are missed or vomited, they should report this to the healthcare provider.
• Caregivers should contact their healthcare provider if patient develops signs of a viral respiratory infection.
• Caregivers should be aware that vector shedding may occur primarily through body waste; precautions should be followed for 1 month following infusion and include: sealing disposable diapers in disposable trash bags and discarding into regular trash; proper hand hygiene when coming into direct contact with patient body waste.

Frequently asked questions

• Is Zolgensma a cure for SMA?

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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