Spinraza (nusinersen sodium/PF)
Genetic Disorder Therapy - SMN Protein Deficiency Treatment Intrathecal Vial (Ml)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Nusinersen sodium is an antisense oligonucleotide that binds to the pre-mRNA of survival motor neuron 2 (SMN2).
Nusinersen is a 2'-O-methoxyethyl phosphorothioate-modified antisense oligonucleotide that binds to and modulates the splicing of survival motor neuron 2 (SMN2) pre-mRNA, thereby increasing production of the deficient survival motor neuron (SMN) protein in patients with spinal muscular atrophy.
Spinal muscular atrophy is caused by mutations in the survival motor neuron 1 (SMN1) gene located on chromosome 5q13. Absence of SMN1 leads to reliance on the nearly identical SMN2 gene; however, 80-90% of SMN2 mRNA transcripts exclude exon 7, thus encoding a truncated form of SMN protein that is rapidly degraded. Nusinersen binds specifically to the intronic splicing silencer N-1 (ISS-N1) site located downstream of exon 7 on the SMN2 transcript.
Hybridization of nusinersen to ISS-N1 prevents recruitment of splicing repressors, thus promoting inclusion of exon 7 and subsequent production of full-length, fully functional SMN protein. Autopsy findings from 3 infants who received nusinersen revealed 2.6-fold higher concentrations of SMN2 mRNA containing exon 7 in the thoracic spinal cord than in untreated infants.
Following intrathecal administration of nusinersen, trough plasma concentrations of the drug are relatively low compared with trough CSF concentrations. Intrathecally-administered nusinersen appears to rapidly distribute from the CSF into the systemic circulation, consistent with normal CSF turnover. Mean peak plasma concentrations and area under the concentration-time curve (AUC) of nusinersen increase approximately dose proportionally up to a dose of 12 mg; time to peak plasma concentration ranges from 1.7 to 6 hours, followed by a slow decline over approximately 20 hours.
Intrathecal injection of nusinersen into the CSF allows the drug to be distributed directly to target tissues in the CNS, including motor neurons. Autopsy data reveal that the drug also is distributed within peripheral tissues (e.g., skeletal muscle, liver, kidney). Nusinersen is metabolized by exonuclease-mediated hydrolysis.
Urinary excretion is likely the primary route of elimination for nusinersen and its short-chained metabolites. The mean terminal elimination half-life is estimated to be 135-177 days in CSF and 63-87 days in plasma. At 24 hours post-dose, only 0.5% of an administered dose of nusinersen was recovered in urine.
USES: This medication is used to treat a certain nervous system disorder that can lead to muscle weakness and muscle loss (spinal muscular atrophy). Nusinersen may help improve motor functions (such as crawling, walking).
Generic name: nusinersen sodium/PF
Pronunciation: (NUE-si-NER-sen)
Drug class: Genetic Disorder Therapy - SMN Protein Deficiency Treatment
Therapeutic class: Locomotor System
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Spinraza
Indications
The following indications are listed for Spinraza:
- Spinal Muscular Atrophy
Dosing
Dosage of nusinersen sodium is expressed in terms of nusinersen.
No dosing information is available for this tab.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Spinraza 28 Mg/5 Ml Vial | Maintenance | Inject 5 milliliters (28 mg) over 1-3 minute(s) by intrathecal route every 4 months. |
| Spinraza 50 Mg/5 Ml Vial | Maintenance | Inject 5 milliliters (50 mg) over 1-3 minute(s) by intrathecal route every 14 days for 2 doses. |
| Spinraza 12 Mg/5 Ml Vial | Maintenance | Inject 5 milliliters (12 mg) over 1-3 minute(s) by intrathecal route every 4 months. |
No dosing information is available for this tab.
Drug interactions
Drug interaction studies have not been conducted with nusinersen. In vitro findings indicate that nusinersen is not a substrate for, nor an inhibitor or inducer of, cytochrome P-450 (CYP) isoenzymes or of the various transporters.
There are no contraindication interactions for this drug.
Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
Myelosuppressives; Immunomodulators/Sodium Iodide I 131
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)
CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)
DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)
There are no moderate interactions for this drug.
Contraindications
*None.
There are no contraindication contraindications for this drug.
- Congenital long QT syndrome
- Increased risk of bleeding
- Thrombocytopenic disorder
Adverse reactions
The most common adverse effects occurring in at least 20% of patients with infantile-onset SMA receiving nusinersen and at least 5% more frequently than sham injections include lower respiratory infection and constipation.
The most common adverse effects occurring in at least 20% of patients with later-onset SMA receiving nusinersen and at least 5% more frequently than sham injections include pyrexia, headache, vomiting, and back pain.
More Frequent
- Lower respiratory infection
- Pneumonia
Less Frequent
- Accidental fall
- Anemia
- Aspiration pneumonia
- Atelectasis
- Nephrotoxicity
Rare or Very Rare
- Acquired communicating hydrocephalus
- Acute respiratory distress syndrome
- Acute respiratory failure
- Angioedema
- Chemical arachnoiditis
- Glomerulonephritis
- Hypersensitivity drug reaction
- Hyponatremia
- Hypoxia
- Infection
- Meningitis
- Non-infective meningitis
More Frequent
- Back pain
- Constipation
- Dysphagia
- Fever
- Headache disorder
- Proteinuria
- Upper respiratory infection
- Vomiting
Less Frequent
- Epistaxis
- Flatulence
- Increased risk of bleeding due to coagulation disorder
- Increased troponin-I level
- Infection of ear
- Respiratory tract congestion
- Seasonal allergic rhinitis
- Teething pain
- Thrombocytopenic disorder
- Urinary tract infection
- Weight loss
Rare or Very Rare
- Cough
- Maculopapular rash
- Nasal congestion
- Rhinorrhea
- Skin rash
- Urticaria
Precautions
No enhanced messaging available.
Safety and efficacy of nusinersen have been established in pediatric patients of all ages.
There are no adequate data regarding use of nusinersen in pregnant women.
In animal reproductive studies, developmental toxicity (adverse neurobehavioral effects) was observed when nusinersen was administered by subcutaneous injection to mice throughout organogenesis and lactation.
It is not known whether nusinersen is distributed into human milk; the drug was detected in milk of lactating mice when administered by subcutaneous injection. The effects of nusinersen on nursing infants or on milk production are unknown. The known benefits of breast-feeding should be considered along with the mother's clinical need for nusinersen and any potential adverse effects of the drug or disease on the breast-fed infant.
Clinical studies did not include a sufficient number of patients >=65 years of age to determine whether they respond differently from younger patients.
ICD codes
| Code | Type | Description |
|---|---|---|
| Spinal muscular atrophy | ||
| G12.0 | ICD10CM | Infantile spinal muscular atrophy, type I [werdnig-hoffman] |
| G12.1 | ICD10CM | Other inherited spinal muscular atrophy |
| G12.25 | ICD10CM | Progressive spinal muscle atrophy |
| G12.9 | ICD10CM | Spinal muscular atrophy, unspecified |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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