Natalizumab

VERBATIM (UK SPC section 4.2, subcutaneous presentation): '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.' VERBATIM (US FDA label section 2, intravenous): '300 mg infused intravenously over one hour, every four weeks. Do not give as an intravenous push or bolus'; section 2.4: 'Infuse TYSABRI 300 mg in 100 mL 0.9% Sodium Chloride Injection, USP, over approximately one hour (infusion rate approximately 5 mg per minute).' The final diluted solution has a concentration of 2.6 mg/mL; the vial supplies 300 mg/15 mL (20 mg/mL) and must be diluted only in 0.9% sodium chloride; use within 48 hours of preparation. NO MAXIMUM DOSE is stated: the dose is a single fixed 300 mg with no titration and no explicit maximum figure anywhere in the fetched labels, so maxDose is deliberately left empty rather than restating the dose. SPECIALIST SUPERVISION (verbatim): '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.' In the US, only prescribers registered in the MS TOUCH Prescribing Program may prescribe TYSABRI for multiple sclerosis. REVIEW (verbatim): 'Continued therapy must be carefully reconsidered in patients who show no evidence of therapeutic benefit beyond 6 months ... After 2 years continued therapy should be considered only following a reassessment of the potential for benefit and risk.' EXTENDED INTERVAL DOSING (verbatim, section 4.4): '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. If utilising extended interval dosing, caution is required because the efficacy of extended interval dosing has not been established and the associated benefit/risk balance is currently unknown ... The decrease in PML risk is based on data from intravenous route of administration. No clinical data are available on either the safety or efficacy of this extended interval dosing with subcutaneous route of administration.' ELDERLY (verbatim): 'This medicinal product is not recommended for use in patients aged over 65 years due to a lack of data in this population.' PRIOR IMMUNOSUPPRESSION (verbatim): some patients may have been exposed to immunosuppressive medicinal products (e.g. mitoxantrone, cyclophosphamide, azathioprine) which can cause prolonged immunosuppression even after dosing is discontinued, 'therefore, the physician must confirm that such patients are not immunocompromised before starting treatment.' OBSERVATION AFTER DOSING: SC — natalizumab-naive patients should be observed during the injection and for 1 hour after, for the first six doses; for patients who have already received at least six doses the 1-hour observation may be reduced or removed according to clinical judgement if no injection/infusion reactions have occurred. IV — observe during all infusions and for one hour after the infusion for the first 12 infusions; from the 13th infusion, post-infusion observation according to clinical judgment. HOME/SELF-ADMINISTRATION (SC only): may be considered for patients who have previously tolerated at least six doses well, after evaluation and recommendation by the specialised physician; patients or caregivers must administer at least two doses under the guidance of a healthcare professional, and after a treatment gap of 3 months or more the six subsequent doses must be administered under healthcare-professional supervision. RE-ADMINISTRATION (verbatim): 'The efficacy of re-administration has not been established.' SEPARATE INDICATION NOT ON THIS PAGE: the US label also gives 300 mg intravenously over one hour every four weeks for Crohn's disease, under the CD TOUCH Prescribing Program, with discontinuation if no therapeutic benefit by 12 weeks of induction therapy — that is a different indication and is recorded here only for completeness.