mes; ULN after ZOLGENSMAinfusion. These patients, who were otherwise asymptomatic with normal total bilirubin, weremanaged with systemic corticosteroids, and the abnormalities resolved without clinical sequelae.
Prior to ZOLGENSMA infusion, assess liver function by clinical examination and laboratorytesting (hepatic aminotransferases [AST and ALT], total bilirubin level, and prothrombin time).
Continue to monitor liver function for at least 3 months after ZOLGENSMA infusion (weeklyfor the first month, and then every other week for the second and third months, until results areunremarkable). [see Laboratory Testing and Monitoring to Assess Safety (2.3)] Administersystemic corticosteroid before and after ZOLGENSMA infusion [see Dose and Administration(2.1)].
5.2 Thrombocytopenia
Transient decreases in platelet counts, some of which met the criteria for thrombocytopenia,were observed at different time points after ZOLGENSMA infusion. Monitor platelet countsbefore ZOLGENSMA infusion and on a regular basis afterwards (weekly for the first month;every other week for the second and third months until platelet counts return to baseline) [seeLaboratory Testing and Monitoring to Assess Safety (2.3)].
5.3 Elevated Troponin-I
Transient increases in cardiac troponin-I levels (up to 0.176 µg/L) were observed followingZOLGENSMA infusion in clinical trials. The clinical importance of these findings is not known.
However, cardiac toxicity was observed in animal studies [see Animal Toxicology and/orPharmacology (13.2)]. Monitor troponin-I before ZOLGENSMA infusion and on a regular basisfor at least 3 months afterwards (weekly for the first month, and then monthly for the second andthird months until troponin-I level returns to baseline) [see Laboratory Testing and Monitoringto Assess Safety (2.3)].
6 ADVERSE REACTIONS
The most common adverse reactions (incidence ≥ 5%) were elevated aminotransferases andvomiting.
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction ratesobserved in the clinical trials of a drug cannot be directly compared to rates in the clinical trialsof another product and may not reflect the rates observed in practice.
The safety data described in this section reflect exposure to ZOLGENSMA in four open-labelstudies conducted in the United States, including one completed clinical trial, two ongoingclinical trials, and one ongoing observational long-term follow-up study of the completed trial. Atotal of 44 patients with SMA received intravenous infusion of ZOLGENSMA, 41 patients at orabove the recommended dose, and 3 patients at a lower dose. The patient population ranged inage from 0.3 months to 7.9 months at the time of infusion (weight range 3.0 kg to 8.4 kg).
The most frequent adverse reactions (incidence ≥ 5%) observed in the 4 studies are summarizedin Table 2.
Table 2: Adverse Reactions Following Treatment with ZOLGENSMA (N = 44)
Adverse Reactions Patients
n (%)
Elevated aminotransferasesab
(> ULN) 12 (27.3%)
Vomiting 3 (6.8%)
ULN = upper limit of normal.
a Elevated aminotransferases include elevation of alanine aminotransferase (ALT) and/or aspartate aminotransferase
(AST).
bIn the completed clinical trial, one patient (the first patient infused in that study) was enrolled prior to the protocolamendment instituting administration of prednisolone before and aft |
