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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 MHRA 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, with timely access to MRI. Patients must be monitored for early signs and symptoms of Progressive Multifocal Leukoencephalopathy (PML).
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). 4 for educational guidance). After 2 years of treatment, patients should be re-informed about the risks, especially the increased risk of PML, and should be instructed together with their caregivers on early signs and symptoms of PML.
Resources for the management of hypersensitivity reactions and access to MRI should be available. 4). g. mitoxantrone, cyclophosphamide, azathioprine). These medicinal products have the potential to cause prolonged immunosuppression, even after dosing is discontinued.
4). Posology The recommended dose for subcutaneous administration is 300 mg every 4 weeks. As each pre-filled syringe contains 150 mg natalizumab two pre-filled syringes need to be administered. 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 (intravenous infusion) 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). Any switch in route of administration of the medicinal product should be made 4 weeks after the previous dose. 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 Tysabri 150 mg solution for injection in pre-filled syringe is for subcutaneous (SC) injection only.
Summary of the safety profile The safety profile observed for natalizumab administered subcutaneously was consistent with the known safety profile of natalizumab administered intravenously, with the exception of injection site pain.
The overall frequency of injection site pain was common 4% (3/71) for subjects receiving natalizumab 300 mg, every 4 weeks, by subcutaneous administration. 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 (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 Frequency of adverse reactionsMedDRA System Organ Class 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 Anaemia Thrombocytopenia, Haemolytic anaemia Frequency of adverse reactionsMedDRA System Organ Class Very Common Common Uncommon Rare Not known lymphatic system disorders Immune thrombocytopenic purpura (ITP), Eosinophilia 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 Investigations Hepatic enzyme increased Drug specific antibody present Injury, poisoning and procedural complications Infusion related reaction Description of selected adverse reactions Hypersensitivity reactions Hypersensitivity reactions usually occurred within one hour after completion of the subcutaneous injections.
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 specialised 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.
In anti-JCV antibody positive patients, extended interval dosing of natalizumab (average dosing interval of approximately 6 weeks) is suggested to be associated with a lower PML risk compared to approved dosing. 1). The decrease in PML risk is based on data from intravenous route of administration.
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.
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It is not intended for intravenous (IV) infusion. Two pre-filled syringes should be administered (total dose 300 mg), one after the other without significant delay. The second injection should be administered no later than 30 minutes after the first injection.
The sites for subcutaneous injection are the thigh, abdomen (at least 6 cm away from the navel), or the posterior aspect of the upper arm (the latter only in case of injection by a healthcare professional or a caregiver). The injection should not be made into an area of the body where the skin is irritated, reddened, bruised, infected, or scarred in any way.
When removing the syringe from the injection site, the plunger should be let go of while pulling the needle straight out. Letting go of the plunger will allow the needle guard to cover the needle. The second injection should be more than 3 cm away from the first injection location (see instructions for administration at the end of the package leaflet).
Natalizumab naive patients should be observed during the injection and for 1 hour after for signs and symptoms of injection reactions including hypersensitivity for the first six natalizumab doses. For patients currently receiving natalizumab and who have already received at least six doses, regardless of the route of natalizumab administration used for the first six doses, the 1-hour post-injection observation time for subsequent subcutaneous injections may be reduced or removed according to clinical judgement if the patients have not experienced any injection/infusion reactions.
g. e. who have not experienced hypersensitivity reactions. The decision for a patient to receive injections outside a clinical setting should be made after evaluation and recommendation by the specialised physician. 4 for further information on PML and educational guidance).
e. who have not experienced hypersensitivity reactions. The decision should be made after evaluation and recommendation by the specialised physician. Patients or caregivers must administer at least two doses via SC route (two injections each) under the guidance of a healthcare professional.
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1). In 2-year controlled clinical trials in MS patients receiving natalizumab intravenously, 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 receiving natalizumab intravenously. 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). In the 32-week DELIVER study in MS patients with no prior exposure to natalizumab, persistent anti-natalizumab antibodies developed in 1 subject (4%) from 26 subjects who received natalizumab subcutaneously. Antibodies were detected on only one occasion in another 5 subjects (19%).
1). 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 (intravenously)- and placebo-treated patients. The nature of the infections was generally similar […]
No clinical data are available on either the safety or efficacy of this extended interval dosing with subcutaneous route of administration. 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 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 natalizumab 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. 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 […]