Treatment with Spinraza should only be initiated by a physician with experience in the management of spinal muscular atrophy (SMA). The decision to treat should be based on an individualised expert evaluation of the expected benefits of treatment for that individual, balanced against the potential risk of treatment with Spinraza.
Patients with profound hypotonia and respiratory failure at birth, where Spinraza has not been studied, may not experience a clinically meaningful benefit due to severe survival motor neuron (SMN) protein deficiency. Posology Two dosing regimens are available.
A low dose regimen of 12 mg, and a high dose regimen of 50/28 mg. Spinraza treatment should be initiated as early as possible after diagnosis. Low dose regimen This regimen is administered with a loading dose of 12 mg on Day 0, 14, 28 and 63, and a maintenance dose of 12 mg once every 4 months thereafter.
High dose regimen A 50 mg loading dose should be administered on Day 0 and on Day 14. A maintenance dose of 28 mg should be administered once every 4 months thereafter. Switching low dose regimen to the high dose regimen Patients currently treated with Spinraza 12 mg may be transitioned to the 50/28 mg dosing regimen with one loading dose of 50 mg administered at least 4 months (+/- 14 days) after the last dose of 12 mg.
The maintenance dose of 28 mg should be administered once every 4 months thereafter. Duration of treatment The need for continuation of therapy should be reviewed regularly and considered on an individual basis depending on the patient’s clinical presentation and response to the therapy.
Missed or delayed doses If a loading or a maintenance dose is delayed or missed, Spinraza should be administered according to the schedule in Table 1 and Table 2 below for the 12 mg and 50/28 mg dosing regimens, respectively.
Table 1:
Recommendations for delayed or missed dose for 12 mg dosing regimen Delayed or Missed dose Timing of Dosing Administration Loading dose • Administer the delayed or missed loading dose as soon as possible with at least 14 days between doses; continue with subsequent doses on the prescribed intervals from the last dose.
g. if the third loading dose is administered 30 days late at Day 58 (instead of the original schedule at Day 28), then the fourth loading dose should be administered 35 days later at Day 93 (instead of the original schedule at Day 63) with a maintenance dose 4 months thereafter.
Maintenance dose Timing of Dosing Administration > 4 to < 8 months from last dose • Administer the delayed maintenance dose as soon as possible; then • The next maintenance dose per the original scheduled date, as long as these two doses are administered at least 14 days apart*; ≥ 8 to < 16 months from last dose • Administer the missed dose as soon as possible and then the next dose 14 days later*; ≥ 16 to < 40 months from last dose • Administer the missed dose as soon as possible and then the next dose 14 days later, followed by a third dose 14 days later*; ≥ 40 months from last dose • Administer the entire loading regimen on the prescribed intervals (Days 0, 14, 28 and 63)*; * Then subsequently to the above recommendations, a maintenance dose 4 months after the last dose should be administered and repeated every 4 months.
5 months, administer the missed 50 mg loading dose as soon as possible; administer the 28 mg maintenance dose per the original scheduled date, as long as these two doses are administered at least 14 days apart; then administer 28 mg every 4 months thereafter.
5 months, administer the missed 50 mg loading dose as soon as possible; followed by the 28 mg maintenance dose 14 days later, then administer the next 28 mg maintenance dose 4 months thereafter. 5 months, restart regimen. Maintenance dose <8 months from last dose • Administer the missed dose as soon as possible; then • Administer the next maintenance dose per the original scheduled date, as long as these two doses are administered at least 14 days apart; then • Administer next maintenance doses every 4 months thereafter.
8 months to <12 months from last dose • Administer the delayed dose as soon as possible; then • Administer one additional maintenance dose 14 days later; then • Administer next maintenance doses every 4 months thereafter ≥12 months from last dose • Restart regimen Special populations Renal impairment Nusinersen has not been studied in patients with renal impairment.
The safety and efficacy in patients with renal impairment has not been established and they should be closely observed. Hepatic impairment Nusinersen has not been studied in patients with hepatic impairment. 2). Method of administration Spinraza is for intrathecal use by lumbar puncture.
Treatment should be administered by health care professionals experienced in performing lumbar punctures. Spinraza is administered as an intrathecal bolus injection over 1 to 3 minutes, using a spinal anaesthesia needle. The injection must not be administered in areas of the skin where there are signs of infection or inflammation.
It is recommended that the volume of cerebral spinal fluid (CSF), equivalent to the volume of Spinraza to be injected, is removed from the patient prior to administration of Spinraza. Sedation may be required to administer Spinraza, as indicated by the clinical condition of the patient.
Ultrasound (or other imaging techniques) may be considered to guide intrathecal administration of Spinraza, particularly in younger patients and in patients with […]