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Tysabri is a brand name for Natalizumab. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Tysabri is indicated as single disease modifying therapy in adults with highly active relapsing remitting multiple sclerosis (RRMS) for the following patient groups: • Patients with highly active disease despite a full and adequate course of treatment with at least one disease modifying therapy (DMT) (for exceptions…
Verbatim from this product's EMA label. Tap a section to expand.
Therapy is to be initiated and continuously supervised by specialised physicians experienced in the diagnosis and treatment of neurological conditions, in centres with timely access to MRI. Patients treated with this medicinal product must be given the Patient Card and be informed about the risks of the medicinal product (see also package leaflet).
After 2 years of treatment, patients should be re-informed about the risks, especially the increased risk of Progressive Multifocal Leukoencephalopathy (PML), and should be instructed together with their caregivers on early signs and symptoms of PML.
3 Resources for the management of hypersensitivity reactions and access to MRI should be available. g. mitoxantrone, cyclophosphamide, azathioprine). These medicinal products have the potential to cause prolonged immunosuppression, even after dosing is discontinued.
4). Posology Tysabri 300 mg is administered by intravenous infusion once every 4 weeks. Continued therapy must be carefully reconsidered in patients who show no evidence of therapeutic benefit beyond 6 months. Data on the safety and efficacy of natalizumab at 2 years were generated from controlled, double– blind studies.
After 2 years continued therapy should be considered only following a reassessment of the potential for benefit and risk. 4). 4). Special populations Elderly This medicinal product is not recommended for use in patients aged over 65 years due to a lack of data in this population.
Renal and hepatic impairment Studies have not been conducted to examine the effects of renal or hepatic impairment. The mechanism for elimination and results from population pharmacokinetics suggest that dose adjustment would not be necessary in patients with renal or hepatic impairment.
Paediatric population The safety and efficacy of this medicinal product in children and adolescents up to 18 years have not been established. 1. Method of administration This medicinal product is for intravenous use. 6). 6), the infusion is to be administered over approximately 1 hour, and patients are to be observed during the infusion and for 1 hour after the completion of the infusion for signs and symptoms of hypersensitivity reactions.
After the first 12 intravenous Tysabri doses, patients should continue to be observed during infusion. If the patients have not experienced any infusion reactions, the post dose observation time may be reduced or removed according to clinical judgement.
8%). 6%). In clinical trials in 6 786 patients treated with natalizumab (intravenous infusion and subcutaneous injection), the most frequently occurring adverse reactions were headache (32%), nasopharyngitis 11 (27%), fatigue (23%), urinary tract infection (16%), nausea (15%), arthralgia (14%), and dizziness (11%) associated with natalizumab administration.
Tabulated list of adverse reactions Adverse reactions arising from clinical studies, post-authorisation safety studies and spontaneous reports are presented in Table 1, below.
Within the system organ classes they are listed under the following headings:
Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1 000 to <1/100); Rare (≥1/10 000 to <1/1 000); Very rare (<1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 1. Adverse reactions MedDRA System Organ Class Frequency of adverse reactions Very Common Common Uncommon Rare Not known Infections and infestations Nasopharyngitis Urinary tract infection Herpes infection Progressive multifocal leukoencephalopathy Herpes ophthalmic Meningoencephalitis herpetic JC virus granule cell neuropathy Necrotising herpetic retinopathy Blood and lymphatic system disorders Anaemia Thrombocytopenia, Immune thrombocytopenic purpura (ITP) Eosinophilia Haemolytic anaemia Nucleated red cells Immune system disorders Hypersensitivity Anaphylactic reaction Immune reconstitution inflammatory syndrome Nervous system disorders Dizziness Headache Vascular disorders Flushing Respiratory, thoracic and mediastinal disorders Dyspnoea Gastrointestinal disorders Nausea Vomiting Hepatobiliary disorders Hyperbilirubinaemia Liver injury Skin and subcutaneous tissue disorders Pruritus Rash Urticaria Angioedema Musculoskeletal and connective tissue disorders Arthralgia General disorders and administration site conditions Fatigue Pyrexia Chills Infusion site reaction Injection site reaction Face oedema 12 MedDRA System Organ Class Frequency of adverse reactions Very Common Common Uncommon Rare Not known Investigations Hepatic enzyme increased Drug specific antibody present Injury, poisoning and procedural complications Infusion related reaction Description of selected adverse reactions Infusion-related reactions (IRR) In 2-year controlled clinical trials in MS patients, an infusion-related event was defined as an adverse event occurring during the infusion or within 1 hour of the completion of the infusion.
Traceability In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded. Progressive Multifocal Leukoencephalopathy (PML) Use of this medicinal product has been associated with an increased risk of PML, an opportunistic infection caused by JC virus, which may be fatal or result in severe disability.
Due to this increased risk of developing PML, the benefits and risks of treatment should be individually reconsidered by the specialist physician and the patient; patients must be monitored at regular intervals throughout and should be instructed together with their caregivers on early signs and symptoms of PML.
JC virus also causes JCV granule cell neuronopathy (GCN) which has been reported in patients treated with this medicinal product. e. cerebellar syndrome). The following risk factors are associated with an increased risk of PML: • The presence of anti-JCV antibodies.
• Treatment duration, especially beyond 2 years. After 2 years all patients should be re-informed about the risk of PML with the medicinal product. • Immunosuppressant use prior to receiving the medicinal product. Patients who are anti-JCV antibody positive are at an increased risk of developing PML compared to patients who are anti-JCV antibody negative.
, are anti-JCV antibody positive and have received more than 2 years of therapy with this medicinal product and have received prior immunosuppressant therapy) have a significantly higher risk of PML. In anti-JCV antibody positive natalizumab treated patients who have not used prior immunosuppressants the level of anti-JCV antibody response (index) is associated with the level of risk for PML.
5 In anti-JCV antibody positive patients, extended interval dosing of Tysabri (average dosing interval of approximately 6 weeks) is suggested to be associated with a lower PML risk compared to approved dosing. 1, Intravenous administration Q6W).
1. Progressive multifocal leukoencephalopathy (PML). 8)). Combination with other DMTs. Known active malignancies, except for patients with cutaneous basal cell carcinoma.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Other brands of Natalizumab in European Union.
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4 Patients restarting natalizumab treatment after a treatment gap ≥ 6 months are to be observed during the infusion and for 1 hour after the completion of the infusion for signs and symptoms of hypersensitivity reactions for the first 12 intravenous infusions after restarting therapy.
Tysabri 300 mg concentrate for solution for infusion must not be administered as a bolus injection.
7%). Events reported more commonly with natalizumab than with placebo included dizziness, nausea, urticaria and rigors. Hypersensitivity reactions In 2-year controlled clinical trials in MS patients, hypersensitivity reactions occurred in up to 4% of patients.
Anaphylactic/anaphylactoid reactions occurred in less than 1% of patients receiving this medicinal product. 4). In post-marketing experience, there have been reports of hypersensitivity reactions which have occurred with one or more of the following associated symptoms: hypotension, hypertension, chest pain, chest discomfort, dyspnoea, angioedema, in addition to more usual symptoms such as rash and urticaria.
Immunogenicity In 10% of patients, antibodies against natalizumab were detected in 2-year controlled clinical trials in MS patients. Persistent anti-natalizumab antibodies (one positive test reproducible on retesting at least 6 weeks later) developed in approximately 6% of patients.
Antibodies were detected on only one occasion in an additional 4% of patients. Persistent antibodies were associated with a substantial decrease in the effectiveness of natalizumab and an increased incidence of hypersensitivity reactions.
4). If, after approximately 6 months of therapy, persistent antibodies are suspected, either due to reduced efficacy or due to occurrence of infusion-related events, they may be detected and confirmed with a subsequent test 6 weeks after the first positive test.
Given that efficacy may be reduced, or the incidence of hypersensitivity or infusion-related reactions may be increased in a patient with persistent antibodies, treatment should be discontinued in patients who develop persistent antibodies.
5 per patient-year in both natalizumab- and placebo-treated patients. The nature of the infections was generally similar in natalizumab- and placebo-treated patients. A case of cryptosporidium diarrhoea was reported in MS clinical trials.
In other clinical trials, cases of additional opportunistic infections have been reported, some of which were fatal. The majority of patients did not interrupt natalizumab therapy during infections and recovery occurred with appropriate treatment.
13 In clinical trials, herpes infections (Varicella-Zoster virus, Herpes-simplex virus) occurred slightly more frequently in natalizumab-treated patients than in placebo-treated patients. In post-marketing experience, serious, life-threatening, and sometimes fatal cases of encephalitis and meningitis caused by herpes simplex or varicella zoster have been reported in […]
For further information, refer to the Healthcare Professional Guide. Patients considered at high risk with this treatment should only continue the treatment if the benefits outweigh the risks. For the estimation of PML risk in the different patient subgroups, please refer to the Healthcare Professional Guide.
Anti-JCV antibody testing Anti-JCV antibody testing provides supportive information for risk stratification of treatment with this medicinal product. Testing for serum anti-JCV antibody prior to initiating therapy or in patients receiving the medicinal product with an unknown antibody status is recommended.
Anti-JCV antibody negative patients may still be at risk of PML for reasons such as a new JCV infection, fluctuating antibody status or a false negative test result. Re-testing of anti-JCV antibody negative patients every 6 months is recommended.
Retesting low index patients who have no history of prior immunosuppressant use every 6 months once they reach the 2-year treatment point is recommended. The anti-JCV antibody assay (ELISA) should not be used to diagnose PML. Use of plasmapheresis/plasma exchange (PLEX) or intravenous immunoglobulin (IVIg) can affect meaningful interpretation of serum anti-JCV antibody testing.
e. 6 months = 5 half-lives for immunoglobulins). For further information on anti-JCV antibody testing please see the Healthcare Professional Guide. MRI screening for PML Before initiation of treatment with this medicinal product, a recent (usually within 3 months) MRI should be available as a reference and be repeated at least on a yearly basis.
g. on a 3 to 6 monthly basis) using an abbreviated protocol should be considered for patients at higher risk of PML. , are anti-JCV antibody positive and have received more than 2 years of therapy with this medicinal product and have received prior immunosuppressant therapy), or • Patients with a high anti-JCV antibody index who have received more than 2 years of therapy with this medicinal product and without prior history of immunosuppressant therapy.
5 for patients who have been on treatment with this medicinal product for longer than 2 years (see the Healthcare Professional Guide for further information). PML should be considered as a differential diagnosis in any MS patient taking Tysabri presenting with neurological symptoms and/or new brain lesions in MRI.
Cases of asymptomatic PML based on MRI and positive JCV DNA in the cerebrospinal fluid have been reported. Physicians should refer to the Healthcare Professional Guide for further information on managing the risk of PML in natalizumab-treated patients.
If PML or JCV GCN is suspected, further dosing must be suspended until PML has been excluded. 6 The specialised physician should evaluate the patient to determine if the symptoms are indicative of neurological dysfunction and, if so, whether these symptoms are typical of MS or possibly suggestive of PML or JCV GCN.
If any doubt exists, further evaluation, including MRI scan preferably with contrast (compared with pre-treatment baseline MRI), CSF testing for JC Viral DNA and repeat neurological assessments, should be considered as described in the Healthcare Professional Guide (see Educational guidance).
Once the clinician has excluded PML and/or JCV GCN (if necessary, by repeating clinical, imaging and/or […]