nusinersen

Increases exon 7 inclusion in survival motor neuron-2 messenger ribonucleic acid (mRNA) transcripts, which results in increased production of full-length survival motor neuron protein.

Therapeutic effects:

Reduction in risk of death or permanent ventilation and improvement in motor skills.

Pharmacokinetics ⬆ ⬇

Absorption: Delivered via intrathecal injection into cerebrospinal fluid (CSF).

Distribution: Distributed within CNS and peripheral tissues (skeletal muscle, liver, and kidney).

Metabolism/Excretion: Metabolized via exonuclease (3’- and 5’)-mediated hydrolysis; primarily excreted in urine.

Half-Life: 135–177 days (CSF); 63–87 days (plasma).

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IT	unknown	1.7–6 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

None.

Use Cautiously in:

OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash

EENT: ear infection

GI: constipation, vomiting, flatulence

GU: GLOMERULONEPHRITIS, urinary tract infection

Hemat: BLEEDING, thrombocytopenia

Metab: weight loss

MS: back pain

Neuro: headache

Resp: lower respiratory tract infection

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

IT (Adults and Children ): Loading dose: 12 mg every 14 days for 3 doses; then 12 mg given 30 days after the third dose; Maintenance dose: 12 mg every 4 mo.

Availability ⬆ ⬇

Solution for injection: 2.4 mg/mL

Assessment ⬆ ⬇

Assess motor development prior to and periodically during therapy.

Lab Test Considerations:

May cause bleeding. Monitor platelet count, prothrombin time, and activated partial thromboplastin time at baseline, prior to each injection, and as needed.
- May cause renal toxicity. Monitor quantitative spot urine protein testing at baseline, prior to each injection and as needed. For urinary protein concentration >0.2 g/L, consider repeat testing and further evaluation.

Implementation ⬆ ⬇

Consider sedation during procedure if needed.
IT: Allow solution to come reach room temperature before administering; do not use external sources of heat. Solution is clear and colorless; do not administer solutions that are discolored or contain particulate matter. Withdraw 12 mg (5 mL) of nusinersen from vial into syringe; discard unused solution in vial. Consider ultrasound or other imaging techniques to guide intrathecal administration, particularly in younger patients. Remove 5 mL cerebrospinal fluid prior to administration. Solution is stable if refrigerated for up to 14 days; protect from light.
Rate: Administer as an intrathecal bolus injection over 1–3 min. Do not administer in areas of skin infection or inflammation.

Patient/Family Teaching ⬆ ⬇

Explain purpose of nusinersen to patient and caregiver. Emphasize importance of dosing schedule. If a loading dose is missed, administer missed dose as soon as possible and adjust the date for all subsequent doses to maintain recommended interval between doses. If maintenance dose missed <8 mo from last dose, administer missed dose as soon as possible; administer next maintenance dose according to originally scheduled date as long as this dose and missed dose are administered ≥14 days apart. If maintenance dose missed ≥8 mo but <16 mo from last dose, administer missed dose as soon as possible followed by another dose 14 days later; administer next maintenance dose 4 mo thereafter. If maintenance dose missed ≥16 mo but <40 mo from last dose, administer missed dose as soon as possible followed by two additional doses 14 days apart; administer next maintenance dose 4 mo thereafter. If maintenance dose missed ≥40 mo from last dose, restart dosing recommended in Route/Dosage section.
Advise patient and caregiver to notify health care professional immediately if signs and symptoms of bleeding (unexpected bleeding, blood in stools or urine) or renal toxicity (edema, dyspnea) occur.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇