Nusinersen

Indications

Nusinersen is used for: Spinal Muscular Atrophy

Adult Dose

Spinal Muscular Atrophy Indicated for spinal muscular atrophy (SMA) in children and adults 12 mg intrathecally per administration Initial: 4 loading doses; administer the first 3 doses at 14-day intervals and the fourth dose 30 days after the third dose Maintenance: One dose every 4 months

Child Dose

Spinal Muscular Atrophy Indicated for spinal muscular atrophy (SMA) in children and adults Safety and effectiveness have been established in children aged newborn to 17 years 12 mg intrathecally per administration Initial: 4 loading doses; administer the first 3 doses at 14-day intervals and the fourth dose 30 days after the third dose Maintenance: One dose every 4 months

Renal Dose

Administration

Intrathecal Preparation Obtain laboratory testing before each dose (see Dosing) Use aseptic technique Each vial is intended for single dose only Store drug in the carton in a refrigerator until time of use Allow the vial to warm to room temperature (25°C/77°F) prior to administration; do not use external heat sources Inspect vial content for particulate matter and discoloration prior to administration; do not administer if visible particulates are observed or if the liquid in the vial is discolored (should be clear and colorless) Use of external filters not required Withdraw 12 mg (5 mL) from the single-dose vial into a syringe and discard unused contents (ie, overfill) of the vial Administer within 4 hr of removal from vial Intrathecal Administration For intrathecal use only Consider sedation as indicated by the clinical condition of the patient Consider ultrasound or other imaging techniques to guide intrathecal administration of, particularly in younger patients Prior to administration, remove 5 mL of cerebrospinal fluid Administer as an intrathecal bolus injection over 1-3 minutes using a spinal anesthesia needle Do not administer in areas of the skin where there are signs of infection or inflammation

Contra Indications

Precautions

Coagulation Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been observed after administration of some antisense oligonucleotides Obtain platelet count and coagulation laboratory testing at baseline and prior to each administration and as clinically needed Renal toxicity Nusinersen is present in and excreted by the kidney Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides Conduct quantitative spot urine protein testing (preferably using a first morning urine specimen) at baseline and prior to each dose For urinary protein concentration >0.2 g/L, consider repeat testing and further evaluation

Pregnancy-Lactation

Pregnancy There are no adequate data on the developmental risk associated with use in pregnant women No adverse effects on embryofetal development were observed in animal studies in which nusinersen was administered by subcutaneous injection to mice and rabbits during pregnancy Lactation Unknown if distributed in human breast milk; detected in milk of lactating mice when administered by subcutaneous injection Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Interactions

Adverse Effects

Side effects of Nusinersen : >10% Headache (50%) Lower respiratory infection (43%) Back pain (41%) Postlumbar puncture syndrome (41%) Upper respiratory infection (39%) Elevated urine protein (33%) Constipation (30%) Atelectasis (14%) Thrombocytopenia (11%) 1-10% Upper respiratory tract congestion (6%) Aspiration (5%) Ear infection (5%) Emergent treatment antidrug antibodies (4%)

Mechanism of Action

An antisense oligonucleotide (ASO) designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency Using in vitro assays and studies in transgenic animal models of SMA, nusinersen was shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein