WHY SPINRAZA/SAFETY
The SPINRAZA safety profile was evaluated in clinical trials1
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 and later-onset spinal muscular atrophy (SMA), 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 the sham-controlled studies for patients with infantile-onset and later-onset SMA, 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.
Did you know that SPINRAZA has been studied in the longest clinical trial program in SMA to date?2
Most common adverse events (AEs) in ENDEAR
AEs that occurred in ≥5% of patients treated with SPINRAZA and ≥5% more frequently or ≥2 times as frequently than in control patients with infantile-onset SMA or early-onset SMA.
ENDEAR
*Loading doses followed by 12 mg (5 mL) once every 4 months
†Includes adenovirus infection, bronchiolitis, 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 AEs in CHERISH
AEs as occurred in ≥5% of patients treated with SPINRAZA 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 considerations
- Serious AEs 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
Postmarketing events
- The following AEs 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 observed. Hydrocephalus, aseptic meningitis, and hypersensitivity reactions (eg, angioedema, urticaria, rash) have also been reported