SPINRAZA Solution for injection Ref.[9367] Active ingredients: Nusinersen

Lumbar puncture procedure

There is a risk of adverse reactions occurring as part of the lumbar puncture procedure (e.g. arachnoiditis, headache, back pain, vomiting; see section 4.8). Potential difficulties with this route of administration may be seen in very young patients and those with scoliosis. The use of ultrasound or other imaging techniques to assist with intrathecal administration of Spinraza, can be considered at the physician’s discretion. Should arachnoiditis be suspected, an MRI should be performed to confirm arachnoiditis and the extent of the inflammation. Identification of arachnoiditis precludes the use of the injection site until local inflammation has been ruled out.

Thrombocytopenia and coagulation abnormalities

Thrombocytopenia and coagulation abnormalities, including acute severe thrombocytopenia, have been observed after administration of other subcutaneously or intravenously administered antisense oligonucleotides. If clinically indicated, platelet and coagulation laboratory testing is recommended prior to administration of Spinraza.

Renal toxicity

Renal toxicity has been observed after administration of other subcutaneously and intravenously administered antisense oligonucleotides. If clinically indicated, urine protein testing (preferably using a first morning urine specimen) is recommended. For persistent elevated urinary protein, further evaluation should be considered.

Hydrocephalus

There have been reports of communicating hydrocephalus not related to meningitis or bleeding in patients treated with nusinersen in the post-marketing setting. Some patients were implanted with a ventriculo-peritoneal shunt. In patients with decreased consciousness, an evaluation for hydrocephalus should be considered. The benefits-and risks of nusinersen treatment in patients with a ventriculo-peritoneal shunt are unknown at present and the maintenance of treatment needs to be carefully considered.

Excipients

Sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per 5 ml vial, that is to say essentially ‘sodium-free’.

Potassium

This medicinal product contains potassium, less than 1 mmol (39 mg) per 5 ml vial, i.e. essentially ‘potassium-free’.

No interaction studies have been performed. In vitro studies indicated that nusinersen is not an inducer or inhibitor of CYP450 mediated metabolism. In vitro studies indicate that the likelihood for interactions with nusinersen due to competition for plasma protein binding, or competition with or inhibition of transporters is low.

Pregnancy

There are no or limited amount of data from the use of nusinersen in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of nusinersen during pregnancy.

Breast-feeding

It is unknown whether nusinersen/metabolites are excreted in human milk.

A risk to the newborn/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from nusinersen therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

In toxicity studies in animals no effects on male or female fertility were observed (see section 5.3). There are no data available on the potential effects on fertility in humans.

Nusinersen has no or negligible influence on the ability to drive and use machines .

Summary of safety profile

The most common adverse reactions (ADRs) associated with the administration of Spinraza by lumbar puncture were headache, vomiting and back pain.

The safety of Spinraza was assessed in clinical trials based on two Phase 3 clinical studies in infants (CS3B) and children (CS4) with SMA, together with one Phase 2 study in infants and children with SMA (CS7) and open-label studies including presymptomatic infants (CS5) genetically diagnosed with SMA and infants and children with SMA. Study CS11 enrolled infantile and later-onset patients including those who had completed studies CS3B, CS4 and CS12. Of the 352 patients who received Spinraza up to a maximum of 10.8 years, 256 patients received treatment for at least 5 years.

Tabulated list of adverse reactions

The safety assessment of Spinraza is based on data from patients from clinical trials and from post-marketing surveillance. The ADRs associated with Spinraza administration are summarised in Table 2.

The assessment of undesirable effects is based on the following frequency data: Very common (≥1/10), Not known (cannot be estimated from the available data).

Table 2. Adverse reactions related to Spinraza administration:

^* Adverse reactions considered related to the lumbar puncture procedure. These reactions can be considered manifestations of post-lumbar puncture syndrome. These adverse reactions were reported in CS4 (later onset SMA) with an incidence at least 5% higher in patients treated with Spinraza (n=84) compared to Sham control.
^** e.g. angiodema, urticaria and rash.

Events of communicating hydrocephalus have been observed in the post-marketing setting (see section 4.4).

Description of selected adverse reactions

Adverse reactions associated with the administration of Spinraza by lumbar puncture have been observed. The majority of these are reported within 72 hours of the procedure. The incidence and severity of these events were consistent with events expected to occur with lumbar puncture. No serious complications of lumbar puncture, such as serious infections, have been observed in the clinical trials of Spinraza.

Some adverse reactions commonly associated with lumbar puncture (e.g. headache and back pain) could not be assessed in the infant population exposed to Spinraza due to the limited communication appropriate for that age group.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.