Warnings and precautions1
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been observed after administration of some ASOs. In a clinical study, 6 of 56 (11%) patients treated with SPINRAZA with normal or above normal platelet levels at baseline developed a platelet level below the lower limit of normal compared to 0 of 28 sham procedure–control 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 a clinical study (mean treatment exposure 7 months), 17 of 51 (33%) patients treated with SPINRAZA had elevated urine protein, compared to 5 of 25 (20%) sham-control patients. In a group of patients with later-onset SMA (mean treatment exposure 34 months), 36 of 52 (69%) had elevated urine protein. Patients may be at increased risk of renal toxicity.
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:
No elevations in serum creatinine or cystatin C were observed in studies with SPINRAZA. 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.
No patient had a platelet count less than 50,000 cells per microliter in this study and no patient developed a sustained low platelet count despite continued drug exposure.
Infantile-onset (Type 1) SMA treated with SPINRAZA