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1 X 12 mg / 1.2 ml
The recommended dose is 12 mg/day administered by intravenous infusion for 2 treatment courses.
1) Initial treatment course: 12 mg/day for 5 consecutive days (60 mg total dose)
2) Second treatment course: 12 mg/day for 3 consecutive days (36 mg total dose) administered 12 months after the initial treatment course.
Missed doses should not be given on the same day as a scheduled dose.
Follow-up of patients: The therapy is recommended as 2 treatment courses with safety follow-up of patients from initiation of treatment and until 48 months after the last infusion.
Pre-treatment: Patients should be pre-treated with corticosteroids immediately prior to Alemtuzumab administration on each of the first 3 days of any treatment course. In clinical trials, patients were pre-treated with 1,000 mg methylprednisolone for the first 3 days of each Alemtuzumab treatment course. Additionally, pretreatment with antihistamines and/or antipyretics prior to Alemtuzumab administration may also be considered.
Oral prophylaxis for herpes infection should be administered to all patients starting on the first day of each treatment course and continuing for a minimum of 1 month following treatment with Alemtuzumab. In clinical trials, patients were administered aciclovir 200 mg twice a day or equivalent.
Elderly: Clinical studies did not include any patients aged over 55 years old. It has not been determined whether they respond differently than younger patients.
Renal or hepatic impairment: Alemtuzumab has not been studied in patients with renal or hepatic impairment.
Paediatric population: The safety and efficacy of Alemtuzumab in children with MS aged 0 to 18 years have not yet been established. There is no relevant use of Alemtuzumab in children aged from birth to less than 10 years for the treatment of multiple sclerosis. No data are available.
Method of administration: Alemtuzumab must be diluted before infusion. The diluted solution should be administered by intravenous infusion over a period of approximately 4 hours.
For instructions on dilution of the medicinal product before administration: See prescrbing information for full details.
Indicated for adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features.
Hypersensitivity to the active substance, or to any of the excipients.
Human Immunodeficiency Virus (HIV) infection.
Patients with severe active infection until resolution.
This drug is not recommended for patients with inactive disease or those stable on current therapy.
Patients treated with LEMTRADA must be given the Patient Alert Card and the Patient Guide. Before treatment, patients must be informed about the risks and benefits, and the need to commit to followup from treatment initiation until 48-months after the last infusion of the second LEMTRADA.
Autoimmunity: Treatment may result in the formation of autoantibodies and increase the risk of autoimmune mediated conditions including immune thrombocytopenic purpura (ITP), thyroid disorders or, rarely, nephropathies (e.g. anti-glomerular basement membrane disease). Caution should be exercised in patients with previous autoimmune conditions other than MS, although available data suggests there is no worsening of pre-existing autoimmune conditions after Alemtuzumab treatment.
Immune Thrombocytopenic Purpura (ITP): Serious events of ITP have been observed in approximately 1% of patients treated in controlled clinical trials in MS. In a controlled clinical trial in patients with MS, one patient developed ITP that went unrecognised prior to implementation of monthly blood monitoring requirements and died from intracerebral haemorrhage. ITP onset has generally occurred between 14 and 36 months after first exposure. Symptoms of ITP could include (but are not limited to) easy bruising, petechiae, spontaneous mucocutaneous bleeding (e.g., epistaxis, haemoptysis), heavier than normal or irregular menstrual bleeding. Haemoptysis may also be indicative of anti-GBM disease, and an appropriate differential diagnosis has to be undertaken. Remind the patient to remain vigilant for symptoms they may experience and to seek immediate medical help if they have any concerns. Complete blood counts with differential should be obtained prior to initiation of treatment and at monthly intervals thereafter until 48 months after the last infusion. After this period of time, testing should be performed based on clinical findings suggestive of ITP. If ITP is suspected a complete blood count should be obtained immediately. If ITP onset is confirmed, appropriate medical intervention should be promptly initiated, including immediate referral to a specialist. Data from clinical trials in MS has shown that adherence to the blood monitoring requirements and education relative to signs and symptoms of ITP has led to early detection and treatment of ITP with most cases responding to first-line medical therapy.
The potential risk associated with retreatment with this drug following the occurrence of ITP is unknown.
Nephropathies: Nephropathies, including anti-glomerular basement membrane (anti-GBM) disease, have been observed in 0.3% of patients in clinical trials in MS and generally occurred within 39 months following the last administration of Alemtuzumab. In clinical trials, there were 2 cases of anti-GBM disease. Both cases were serious, were identified early through clinical and laboratory monitoring, and had a positive outcome after treatment.
Clinical manifestations of nephropathy may include elevation in serum creatinine, haematuria, and/or proteinuria. While not observed in clinical trials, alveolar haemorrhage manifested as haemoptysis may occur with anti-GBM disease. Haemoptysis may also be indicative of ITP, and an appropriate differential diagnosis has to be undertaken. The patient should be reminded to remain vigilant for symptoms they may experience and to seek immediate medical help if they have any concerns. Anti-GBM disease may lead to renal failure requiring dialysis and/or transplantation if not treated rapidly and can be life-threatening if left untreated. Serum creatinine levels should be obtained prior to initiation of treatment and at monthly intervals thereafter until 48 months after the last infusion. Urinalysis with microscopy should be obtained prior to initiation and at monthly intervals thereafter until 48 months after the last infusion. The observation of clinically significant changes from baseline in serum creatinine, unexplained haematuria, and/or proteinuria, should prompt further evaluation for nephropathies including immediate referral to a specialist. Early detection and treatment of nephropathies may decrease the risk of poor outcomes. After this period of time, testing should be performed based on clinical findings suggestive of nephropathies. The potential risk associated with retreatment with Alemtuzumab following the occurrence of nephropathies is unknown.
Thyroid disorders: Autoimmune thyroid disorders have been observed in an estimated 36% of patients treated with Alemtuzumab 12 mg in clinical trials in MS through 48 months following first Alemtuzumab exposure. The incidence of thyroid events was higher in patients with a medical history of thyroid disorders both in the Alemtuzumab and interferon beta 1a (IFNB-1a) treatment groups. In patients with ongoing thyroid disorder Alemtuzumab should be administered if the potential benefit justifies the potential risks. Observed autoimmune thyroid disorders included hyperthyroidism or hypothyroidism. Most events were mild to moderate in severity. Prior to authorisation, serious events occurred in <1% of patients, with only Basedow’s disease (also known as Graves’ disease), hyperthyroidism, and hypothyroidism occurring in more than 1 patient. Most thyroid events were managed with conventional medical therapy however some patients required surgical intervention. In clinical trials, patients who developed thyroid events were permitted to receive re-treatment with Alemtuzumab. Although experience is limited, patients who were re-treated generally did not experience a worsening in severity of thyroid disorders. Further treatment with Alemtuzumab should be considered on an individual basis taking into account the clinical condition of the respective patient.
Cytopenias: Suspected autoimmune cytopenias such as neutropenia, haemolytic anaemia and pancytopenia have been infrequently reported in clinical trials in MS. Complete blood count results (see above under ITP) should be used to monitor for cytopenias. If a cytopenia is confirmed, appropriate medical intervention should be promptly initiated, including referral to a specialist.
Infusion-associated Reactions (IARs): In controlled clinical trials, infusion associated reactions (IARs) were defined as any adverse event occurring during or within 24 hours of Alemtuzumab infusion. The majority of these may be due to cytokine release during infusion. Most patients treated with Alemtuzumab in controlled clinical trials in MS experienced mild to moderate IARs during and/or up to 24 hours after Alemtuzumab 12 mg administration, which often included headache, rash, pyrexia, nausea, urticaria, pruritus, insomnia, chills, flushing, fatigue, dyspnoea, dysgeusia, chest discomfort, generalised rash, tachycardia, dyspepsia, dizziness, and pain. Serious reactions occurred in 3% of patients including cases of pyrexia, urticaria, atrial fibrillation, nausea, chest discomfort, and hypotension. Clinical manifestations of anaphylaxis may appear similar to clinical manifestations of infusion associated reactions, but would tend to be more severe or potentially life-threatening. Reactions attributed to anaphylaxis have been reported rarely in contrast to infusion associated reactions.
Infections: Infections occurred in 71% of patients treated with Alemtuzumab 12 mg as compared to 53% of patients treated with subcutaneous interferon beta-1a [IFNB 1a](44mcg 3-times weekly) in controlled clinical trials in MS up to 2 years in duration and were predominantly mild to moderate in severity. Infections that occurred more often in Alemtuzumab -treated patients than IFNB 1a patients included nasopharyngitis, urinary tract infection, upper respiratory tract infection, sinusitis, oral herpes, influenza, and bronchitis. Serious infections occurred in 2.7% of patients treated with Alemtuzumab as compared to 1% of patients treated with IFNB-1a in controlled clinical trials in MS. Serious infections in the Alemtuzumab group included: appendicitis, gastroenteritis, pneumonia, herpes zoster, and tooth infection. Infections were generally of typical duration and resolved following conventional medical treatment.
Malignancy: As with other immunomodulatory therapies, caution should be exercised in initiating Alemtuzumab therapy in patients with pre-existing and/or an on-going malignancy. It is not currently known if Alemtuzumab confers a higher risk for developing thyroid malignancies, since thyroid autoimmunity may itself be a risk factor for thyroid malignancies.
Vaccines: It is recommended that patients have completed local immunisation requirements at least 6 weeks prior to treatment with Alemtuzumab. The ability to generate an immune response to any vaccine following Alemtuzumab treatment has not been studied.
See prescribing information for full details.
The most important adverse reactions are autoimmunity (ITP, thyroid disorders, nephropathies, cytopenias), IARs, and infections.
The most common adverse reactions with LEMTRADA (in ≥20% of patients) are rash, headache, pyrexia, and respiratory tract infections.
See prescribing information for full details.
No formal drug interaction studies have been conducted with Alemtuzumab using the recommended dose in patients with MS. In a controlled clinical trial in MS patients recently treated with beta interferon and glatiramer acetate were required to discontinue treatment 28 days before initiating treatment with LEMTRADA.
Pregnancy and Lactation
Pregnancy: There is a limited amount of data from the use of Alemtuzumab in pregnant women. Alemtuzumab should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lactation: It is unknown whether Alemtuzumab is excreted in human milk.
See prescribing information for full details.
In controlled clinical trials two MS patients accidentally received up to 60 mg Alemtuzumab (i.e. total dose for initial treatment course) in a single infusion and experienced serious reactions (headache, rash, and either hypotension or sinus tachycardia). Doses of Alemtuzumab greater than those tested in clinical studies may increase the intensity and/or duration of infusion-associated adverse reactions or its immune effects.
There is no known antidote for Alemtuzumab over dosage. Treatment consists of discontinuation of the medicinal product and supportive therapy.
Compatibility: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except: For intravenous administration, withdraw 1.2 ml of this drugfrom the vial into a syringe using aseptic technique. Inject into 100 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose (5%) solution for infusion.
This medicinal product must not be diluted with other solvents. The bag should be inverted gently to mix the solution.
This formulation contains no antimicrobial preservatives and, therefore, care should be taken to ensure the sterility of the prepared solution. It is recommended that the diluted product be administered immediately.
Each vial is intended for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Storage: Concentrate: Store in a refrigerator (2°C – 8°C). Do not freeze. Do not shake. Keep the vial in the outer carton in order to protect from light.