Nusinersen

Mechanism :

Nusinersen is an antisense oligonucleotide (ASO) that targets the survival motor neuron-2 (SMN2) gene in order to treat SMA brought on by mutations in chromosome 5q mutations that result in SMN protein shortage.

Indication :

Treatment of Spinal muscular atrophy (SMA).

Contraindications :

General Details

When FDA approval was taken, the product label reported no contraindications for utilization of the drug in patients with spinal muscular atrophy (SMA).

Specialized care environment requirement with an qualified physician

Nusinersen therapy needs a qualified physician, well-trained in performing lumbar punctures and intrathecal drug administration. Administration of the drug needs a specialized care environment like a hospital or treatment facility. Treatment may require sedation, USG or other imaging guidance to enable efficient intrathecal administration of the drug.

Hemorrhage, low platelet count

Abnormal coagulation profiles and low platelet count such as acute severe thrombocytopenia, have been seen after administration of antisense oligonucleotides. Hence, patients may be at a higher risk of hemorrhage. Perform a thrombocyte count and coagulation profile testing at baseline, before each administration, and as needed clinically.

Renal dysfunction

Following administration of antisense oligonucleotides, renal toxicity has been observed, along with potentially deadly glomerulonephritis. The kidneys help to eliminate nusinersen. At baseline and before each dosage of nusinersen, it is advisable to perform quantitative spot urine protein testing (ideally using a first morning urine specimen). Consider repeat tests and more evaluation if the urine protein concentration is greater than 0.2 grams/L.

Dosing :

Available as solution for intrathecal administration: 12 mg/5 mL single-dose vial.

Intrathecal dosing:

In adults:

In Infants, Children, and Adolescents:

In Neonates:

Administer 12 mg via intrathecal route every 14 days for the first 3 loading doses. Administer the fourth loading dose 30 days after the third dose. Then, administer a maintenance dose once every 4 months. If there is a delay in a loading dose, administer the drug as soon as possible, with at least 14 days between doses. A missed maintenance dose may be given as soon as possible and dosing to be continued every 4 months. At baseline and prior to dosing, lab tests to be performed are: • Platelet count • Prothrombin time (PT), activated partial thromboplastin time (aPTT) • Quantitative spot urine protein testing

Adverse Effect :

>10%: Backache, lower respiratory tract infection, upper respiratory tract infection, atelectasis, headache, high urine protein, constipation, low platelet count, post-lumbar puncture syndrome

1-10%: Infection of the ear, aspiration, upper respiratory tract congestion, emergent treatment antidrug antibodies

Lactation :

There is limited data about the presence of the drug in human milk, its effects on breast-fed infants or on the effects on lactogenesis. Prior to administration of the drug in lactating women, consider the risks of neonatal drug exposure, risk of an untreated condition and benefits of breast-feeding. If a breast-fed infant experiences an adverse event associated with a mother treated with the drug, clinicians must report the adverse event to the FDA.

Pregnanacy :

There is not much available data about the utilization of the drug in pregnant females to assess drug-related toxicity. Animal data found an association of developmental toxicity in the form of long-term neuro-behavioral disturbances at all doses tested.