tofersen

Therapeutic Classification: none assigned

Pharmacologic Classification: antisense oligonucleotides

Indications ⬆ ⬇

REMS

Amyotrophic lateral sclerosis in patients who have a mutation in the superoxide dismutase 1 (SOD1) gene.

Action ⬆ ⬇

Antisense oligonucleotide causes degradation of SOD1 mRNA through binding to SOD1 mRNA, which results in a reduction of SOD1 protein synthesis.

Therapeutic effects:

Reduction in neurofilament light chain levels (biomarker of axonal injury and neurodegeneration) in plasma and SOD1 protein levels in CSF.

Pharmacokinetics ⬆ ⬇

Absorption: Extent of absorption unknown.

Distribution: Well distributed to CNS tissues.

Metabolism/Excretion: Metabolized through exonuclease-mediated hydrolysis. Excretion pathway unknown.

Half-Life: 4 wk.

Time/Action Profile ⬆ ⬇

(reduction in neurofilament light chain levels)

ROUTE	ONSET	PEAK	DURATION
Intrathecal	4–8 wk	20–28 wk	≥1 yr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

None.

Use Cautiously in:

OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

EENT: papilledema

MS: arthralgia, myalgia, pain, muscle stiffness, myelitis

Neuro: ↑WBC count in CSF, fatigue, ↑intracranial pressure, ↑protein in CSF, aseptic meningitis, neuralgia, radiculitis

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

IT (Adults ): Loading dose: 100 mg every 14 days × 3 doses; then proceed with maintenance dose. Maintenance dose: 100 mg every 28 days, starting 28 days after 3rd loading dose.

Availability ⬆ ⬇

Solution for intrathecal injection: 6.7 mg/mL

Assessment ⬆ ⬇

Monitor for symptoms of myelitis and radiculitis. If symptoms occur, initiate diagnostic workup, treat as clinically indicated, and consider holding or discontinuing tofersen depending on resolution of symptoms.
Monitor for papilledema and ↑ intracranial pressure. If symptoms occur, initiate diagnostic workup and treatment as clinically indicated.
Monitor for symptoms of aseptic meningitis. If symptoms occur, initiate diagnostic workup and treatment as clinically indicated.

Lab Test Considerations:

May ↑ WBC and protein in CSF.

Implementation ⬆ ⬇

Consider sedation and imaging to guide injection.
Assess for lumbar puncture-related complications prior to and after injection.
IT: Bring vial to room temperature. Solution is clear to slightly yellow. Discard if discolored or contains particulates. Do not shake. Administer IT over 1–3 min using lumbar puncture needle.
- If the 2nd loading dose is missed, administer as soon as possible, and the 3rd loading dose 14 days later. If the 3rd loading dose or a maintenance dose is missed, administer as soon as possible, and the next dose 28 days later.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional if symptoms of myelitis or radiculitis (back pain, extremity weakness, burning or tingling in extremities, ↓ bowel or bladder control, sensitivity to touch), papilledema or ↑ intracranial pressure (headache, nausea, vomiting, visual changes), or aseptic meningitis (fever with headache, nausea, or vomiting; stiff neck; light sensitivity; malaise) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇