Spinraza · 4.8 Undesirable effects · 1

HOS-098082 · has-adverse-reaction-information · PDF-Seite 6

Summary of safety profile The most common adverse reactions (ADRs) associated with the administration of nusinersen by lumbar puncture were headache, vomiting, and back pain. Experience from administering 12 mg dosing regimen The safety of Spinraza 12 mg 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. A total of 385 SMA patients were treated with Spinraza 12 mg or lower and total time on study ranged from 1 to 3940 days (>10 years) (median 2388 days). Experience from administering 50/28 mg dosing regimen The safety of Spinraza at 50/28 mg in infants, children and adults with SMA was assessed in study SM203 and study SM302 in symptomatic SMA patients who ranged in age from 14 days to 65 years at the time of first study dose. A total of 128 SMA patients were treated with Spinraza 50 mg or 28 mg and total time on study ranged from 13 to 1521 days (>4 years) (median 740.5 days). 6 Tabulated list of adverse reactions The safety assessment of nusinersen is based on data from patients from clinical trials and from post- marketing surveillance. The ADRs associated with nusinersen administration are summarised in Table 3. 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 3: Adverse reactions related to Spinraza administration MedDRA System Organ Class Adverse reaction Frequency category Infections and infestations Meningitis Not known Immune system disorders Hypersensitivity* Not known Nervous system disorders Headache** Very common Aseptic meningitis Not known Arachnoiditis Not known Gastrointestinal disorders Vomiting** Very common Musculoskeletal and connective

Auszug; vollständigen Abschnitt im Original lesen.

HOS-098078 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-098077 · has-indication-information · PDF-Seite 2

Spinraza is indicated for the treatment of 5q Spinal Muscular Atrophy.

HOS-098080 · has-interaction-information · PDF-Seite 5

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 5 interactions with nusinersen due to competition for plasma protein binding, or competition with or inhibition of transporters is low.

HOS-098081 · has-pregnancy-information · PDF-Seite 6

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.

HOS-098079 · has-warning-information · PDF-Seite 5

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 12 mg 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’.