er ZOLGENSMA infusion.
One patient in an ongoing non-United States clinical trial initially presented with respiratoryinsufficiency 12 days after ZOLGENSMA infusion and was found to have respiratory syncytialvirus (RSV) and parainfluenza in respiratory secretions. The patient had episodes of serioushypotension, followed by seizures, and was found to have leukoencephalopathy (brain whitematter defects) approximately 30 days after ZOLGENSMA infusion. The patient died afterwithdrawal of life support 52 days after ZOLGENSMA infusion.
6.2 Immunogenicity
In ZOLGENSMA clinical trials, patients were required to have baseline anti-AAV9 antibodytiters of ≤ 1:50, measured using an enzyme-linked immunosorbent assay (ELISA). Evidence ofprior exposure to AAV9 was uncommon. The safety and efficacy of ZOLGENSMA in patientswith anti-AAV9 antibody titers above 1:50 have not been eva luated. Perform baseline testing forthe presence of anti-AAV9 antibodies prior to ZOLGENSMA infusion. Retesting may beperformed if anti-AAV9 antibody titers are reported as > 1:50 [see Dose and Administration(2.1), Laboratory Testing and Monitoring to Assess Safety (2.3)].
Following ZOLGENSMA infusion, increases from baseline in anti-AAV9 antibody titersoccurred in all patients. In the completed clinical trial, anti-AAV9 antibody titers reached at least1:102,400 in every patient, and titers exceeded 1:819,200 in most patients. Re-administration ofZOLGENSMA in the presence of high anti-AAV9 antibody titer has not been eva luated.
7 DRUG INTERACTIONS
Where feasible, adjust a patient’s vaccination schedule to accommodate concomitantcorticosteroid administration prior to and following ZOLGENSMA infusion [see Dose andAdministration (2.1)].
Certain vaccines, such as MMR and varicella, are contraindicated forpatients on a substantially immunosuppressive steroid dose (i.e., ≥ 2 weeks of daily receipt of
20 mg or 2 mg/kg body weight of prednisone or equivalent). Seasonal RSV prophylaxis is notprecluded. (General Best Practice Guidelines for Immunization[www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf], eds2017)8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no available data regarding ZOLGENSMA use in pregnant women. No animalreproductive and developmental toxicity studies have been conducted with ZOLGENSMA.
In the United States general population, the estimated background risk of major birth defects andmiscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
8.2 Lactation
Risk Summary
There is no information available on the presence of ZOLGENSMA in human milk, the effectson the breastfed infant, or the effects on milk production. The developmental and health benefitsof breastfeeding should be considered along with the mother’s clinical need for ZOLGENSMAand any potential adverse effects on the breastfed child from ZOLGENSMA or from theunderlying maternal condition.
8.4 Pediatric Use
Administration of ZOLGENSMA to premature neonates before reaching full-term gestationalage is not recommended, because concomitant treatment with corticosteroids may adverselyaffect neurological development. Delay ZOLGENSMA infusion until the corresponding fulltermgestational age is reached.
There is no information on whether breastfeeding should be restricted in mothers who may be
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