The safety of SPINRAZA® (nusinersen) High Dose Regimen is generally consistent with the known
safety of SPINRAZA Low Dose Regimen1
See Adverse Reactions tab for differences in safety from the study.
Warnings and Precautions
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been observed after administration of some antisense oligonucleotides (ASOs). In the sham-controlled studies for patients with infantile-onset (Study 1) and later-onset (Study 2) spinal muscular atrophy (SMA) who received Low Dose Regimen (12 mg loading doses/12 mg maintenance doses), 24 of 146 (16%) SPINRAZA-treated patients with high, normal, or unknown platelet count at baseline developed a platelet level below the lower limit of normal, compared to 10 of 72 (14%) sham-controlled patients. Because of the risk of thrombocytopenia and coagulation abnormalities from SPINRAZA, patients may be at increased risk of bleeding complications.
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some ASOs. SPINRAZA is present in and excreted by the kidney. In Study 1 and Study 2, 71 of 123 (58%) SPINRAZA-treated patients had elevated urine protein, compared to 22 of 65 (34%) sham-controlled patients. Conduct quantitative spot urine protein testing (preferably using a first morning urine specimen) at baseline and prior to each dose of SPINRAZA. For urinary protein concentration greater than 0.2 g/L, consider repeat testing and further evaluation. Please see lab testing and monitoring information below.
Laboratory testing and monitoring information
Due to the risk of coagulation abnormalities, thrombocytopenia, and renal toxicity, the following laboratory tests are recommended at baseline and prior to each dose of SPINRAZA and as clinically needed:
Conduct quantitative spot urine protein testing (preferably using a first morning urine specimen) at baseline and prior to each dose of SPINRAZA. For urinary protein concentration >0.2 g/L, consider repeat testing and further evaluation.
Please see Adverse Reactions tab above for additional safety information.
ASO, antisense oligonucleotide; SMA, spinal muscular atrophy.
SPINRAZA Low Dose Regimen (12 mg loading doses/12 mg maintenance doses)
Most common adverse reactions (ARs) in infantile-onset SMA (ENDEAR study)2
ARs that occurred in ≥5% of SPINRAZA patients and ≥5% more frequently or ≥2 times as frequently than in control patients with infantile-onset SMA.
ENDEAR
*Low Dose SPINRAZA [see Dosage and Administration (2.1)].
†Includes adenovirus infection, bronchiolitis, bronchitis, bronchitis viral, corona virus infection, influenza, lower respiratory tract infection, lower respiratory tract infection viral, lung infection, parainfluenzae virus infection, pneumonia, pneumonia bacterial, pneumonia influenza, pneumonia moraxella, pneumonia parainfluenzae viral, pneumonia pneumococcal, pneumonia pseudomonal, pneumonia respiratory syncytial viral, pneumonia viral, and respiratory syncytial virus bronchiolitis.
Most common ARs in later-onset SMA (CHERISH study)2
ARs that occurred in ≥5% of SPINRAZA patients and ≥5% more frequently or ≥2 times as frequently than in control patients with later-onset SMA.
CHERISH
‡Loading doses followed by 12 mg (5 mL) once every 6 months.
Additional safety considerations2
- Serious ARs of atelectasis were more frequent in patients treated with SPINRAZA (18%) than in control patients (10%)
- Cases of rash were reported in patients treated with SPINRAZA. One patient, 8 months after starting SPINRAZA treatment, developed painless red macular lesions on the forearm, leg, and foot over an 8-week period. The lesions ulcerated and scabbed over within 4 weeks, and resolved over several months. A second patient developed red macular skin lesions on the cheek and hand 10 months after the start of SPINRAZA treatment, which resolved over 3 months
- Both cases continued to receive SPINRAZA and had spontaneous resolution of the rash
- SPINRAZA may cause a reduction in growth as measured by height when administered to infants. It is unknown whether any effect of SPINRAZA on growth would be reversible with cessation of treatment
- In an open-label clinical study in infants with symptomatic SMA, severe hyponatremia was reported in a patient treated with SPINRAZA requiring salt supplementation for 14 months
SPINRAZA High Dose Regimen (50 mg loading doses/28 mg maintenance doses)
Most common ARs in infantile-onset SMA (DEVOTE study)2
ARs that occurred in ≥5% of SPINRAZA High Dose Regimen patients and ≥5% more frequently or ≥2 times as frequently than matched sham control in patients with infantile-onset SMA.
DEVOTE
Postmarketing experience2
- The following ARs have been identified during post-approval use of SPINRAZA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure
- Serious infections associated with lumbar puncture, such as meningitis, have been reported. Hydrocephalus, aseptic meningitis, and hypersensitivity reactions (eg, angioedema, urticaria, rash), and arachnoiditis have also been reported
AR, adverse reaction; SMA, spinal muscular atrophy.