Miscellaneous musculoskeletal disorders:
Indications for: ZOLGENSMA
Spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.
Limitations of Use:
Safety and efficacy 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.
≥2yrs: not applicable.
Give as a slow IV infusion over 60mins. <2yrs: 1.1×1014 vg/kg (see full labeling). Starting one day prior to Zolgensma infusion: give systemic corticosteroids equivalent to oral prednisolone 1mg/kg/day for 30 days, then taper dose gradually over the next 28 days if LFTs are unremarkable.
Acute serious liver injury. Acute liver failure.
Risk of acute serious liver injury and acute liver failure (esp. preexisting liver impairment or acute hepatic viral infection). ALT, AST, or total bilirubin levels (except due to neonatal jaundice) >2×ULN: not studied. Monitor liver function prior to infusion, weekly for the 1st month, then every other week for the 2nd/3rd months until unremarkable results. Monitor creatinine, CBC prior to infusion. Monitor platelets and troponin-I prior to infusion, weekly for the 1st month, then every other week (platelets) and monthly (troponin-I) for the 2nd/3rd months until levels return to baseline. Monitor for thrombotic microangiopathy (TMA); evaluate for hemolytic anemia and renal dysfunction if thrombocytopenia develops. Increased risk of serious systemic immune response; delay infusion in those with concurrent infections until resolved. Perform baseline anti-AAV9 antibody testing prior to infusion; may retest if titers are >1:50. Consult a specialist if acute serious liver injury/liver failure is suspected, troponin elevations accompanied by signs/symptoms, or TMA occurs. Premature neonates: delay infusion until full-term gestational age is reached.
Adeno-associated virus vector-based gene therapy.
Adjust vaccination schedule to accommodate concomitant corticosteroid use before and after infusion.
Elevated aminotransferases, vomiting; hepatotoxicity, thrombocytopenia, TMA, elevated troponin-I.
Generic Drug Availability:
Customized kit—1 (2–9 vials + alcohol wipes)