Lemtrada

LEMTRADA treatment should only be initiated and supervised by a neurologist experienced in the treatment of patients with multiple sclerosis (MS) in a hospital with ready access to intensive care. Specialists and equipment required for the timely diagnosis and management of adverse reactions, especially myocardial ischaemia and myocardial infarction, cerebrovascular adverse reactions, autoimmune conditions, and infections, should be available.

3 Resources for the management of cytokine release syndrome, hypersensitivity and/or anaphylactic reactions should be available. Patients treated with LEMTRADA must be given the Patient Alert Card and Patient Guide and be informed about the risks of LEMTRADA (see also package leaflet).

Posology The recommended dose of alemtuzumab is 12 mg/day administered by intravenous infusion for 2 initial treatment courses, with up to 2 additional treatment courses if needed. Initial treatment of 2 courses: • First treatment course: 12 mg/day on 5 consecutive days (60 mg total dose) • Second treatment course: 12 mg/day on 3 consecutive days (36 mg total dose) administered 12 months after the first treatment course.

1). Missed doses should not be given on the same day as a scheduled dose. Follow-up of patients The therapy is recommended as an initial treatment of 2 courses with up to 2 additional treatment courses if needed (see posology) with safety follow-up of patients from initiation of the first treatment course and for at least 48 months after the last infusion of the second treatment course.

4). Pre-treatment Patients should be pre-treated with corticosteroids immediately prior to LEMTRADA 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 LEMTRADA treatment course.

Pretreatment with antihistamines and/or antipyretics prior to LEMTRADA administration may also be considered. 4). In clinical trials, patients were administered aciclovir 200 mg twice a day or equivalent. Special populations Elderly Clinical studies did not include any patients aged over 61 years old.

It has not been determined whether they respond differently than younger patients. Renal or hepatic impairment LEMTRADA has not been studied in patients with renal or hepatic impairment. Paediatric population The safety and efficacy of LEMTRADA in children with MS aged 0 to 18 years have not yet been established.

1 years (maximum 12 years), resulting in 8,635 patient-years of safety follow-up. The most important adverse reactions are autoimmunity (ITP, thyroid disorders, nephropathies, cytopenias), IARs, and infections. 4. The most common adverse reactions with LEMTRADA (in ≥20% of patients) were rash, headache, pyrexia, and respiratory tract infections.

Tabulated list of adverse reactions The table below is based on the pooled safety data on all LEMTRADA 12 mg-treated patients during all available follow up in clinical trials. Adverse reactions are listed by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) and Preferred Term (PT).

Frequencies are defined according to the following convention: 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 have been presented in order of decreasing seriousness. 14 Table 1: Adverse reactions in study 1, 2, 3 and 4 observed in LEMTRADA 12 mg treated patients and post-marketing surveillance System Organ Class Very Common Common Uncommon Rare Not known Infections and infestations Upper respiratory tract infection, urinary tract infection, herpes virus infection,1 Herpes zoster infections2, lower respiratory tract infections, gastroenteritis, oral candidiasis, vulvovaginal candidiasis, influenza, ear infection, pneumonia, vaginal infection, tooth infection Onychomycosis, gingivitis, fungal skin infection, tonsillitis, acute sinusitis, cellulitis, tuberculosis, cytomegalovirus infection Listeriosis/l isteria meningitis, Epstein- Barr virus (EBV) infection (including reactivation ) Neoplasms benign, malignant and unspecified (incl.

cysts and polyps) Skin papilloma Blood and lymphatic system disorders Lymphopenia, leukopenia, including neutropenia Lymphadenopath y, immune thrombocytopeni c purpura, thrombocytopeni a, anaemia haematocrit decreased, leukocytosis Pancytopenia, haemolytic anaemia, acquired haemophilia A Haemophagocytic lymphohistiocytosis (HLH), thrombotic thrombocytopenic purpura (TTP) Immune system disorders Cytokine release syndrome*, hypersensitivity including anaphylaxis* Sarcoidosis Endocrine disorders Basedow’s disease, hyperthyrodisim, hypothyroidism Autoimmune thyroiditis including thyroiditis subacute, goitre, anti-thyroid antibody positive Metabolism and nutrition disorders Decreased appetite Psychiatric disorders Insomnia*, anxiety, depression Nervous system disorders Headache* MS relapse, dizziness*, hypoaesthesia, paraesthesia, Sensory disturbance, hyperaesthesia, tension headache, Haemorrha gic stroke**, cervicoceph 15 System Organ Class Very Common Common Uncommon Rare Not known Infections and infestations Upper respiratory tract infection, urinary tract infection, herpes virus infection,1 Herpes zoster infections2, lower respiratory tract infections, gastroenteritis, oral candidiasis, vulvovaginal candidiasis, influenza, ear infection, pneumonia, vaginal infection, tooth infection Onychomycosis, gingivitis, fungal skin infection, tonsillitis, acute sinusitis, cellulitis, tuberculosis, cytomegalovirus infection Listeriosis/l isteria meningitis, Epstein- Barr virus (EBV) infection (including reactivation ) tremor, dysgeusia*, migraine* autoimmune encephalitis alic arterial dissection* * Eye disorders Conjunctivitis, endocrine ophthalmopathy, vision blurred Diplopia Ear and labyrinth disorders Vertigo Ear pain Cardiac disorders Tachycardia* Bradycardia*, palpitations* Atrial fibrillation* Myocardial ischaemia* *, myocardial infarction** Vascular disorders Flushing* Hypotension*, hypertension* Respiratory, thoracic and mediastinal disorders Dyspnoea*, cough, epistaxis, hiccups, oropharyngeal pain, asthma Throat tightness*, throat irritation, pneumonitis Pulmonary alveolar haemorrhag e** Gastrointestinal disorders Nausea* Abdominal pain, vomiting, diarrhoea dyspepsia*, stomatitis Constipation, gastro- oesophageal reflux disease, gingival bleeding, dry mouth, dysphagia, gastrointestinal disorder, haematochezia Hepatobiliary disorders Aspartate aminotransferase increased, alanine aminotransferase increase Cholecystitis including acalculous cholecystitis and acute acalculous cholecystitis Autoimmun e hepatitis, Hepatitis (associated with EBV infection) 16 System Organ Class Very Common Common Uncommon Rare Not known Infections and infestations Upper respiratory tract infection, urinary tract infection, herpes virus infection,1 Herpes zoster infections2, lower respiratory tract infections, gastroenteritis, oral candidiasis, vulvovaginal candidiasis, influenza, ear infection, pneumonia, vaginal infection, tooth infection Onychomycosis, gingivitis, fungal skin infection, tonsillitis, acute sinusitis, cellulitis, tuberculosis, cytomegalovirus infection Listeriosis/l isteria meningitis, Epstein- Barr virus (EBV) infection (including reactivation ) Skin and subcutaneous tissue disorders Urticaria*, rash*, pruritus*, generalised rash* Erythema*, ecchymosis, alopecia, hyperhidrosis, acne, skin lesion, dermatitis Blister, night sweats, swelling face, eczema, vitiligo, alopecia areata Musculoskeletal and connective tissue disorders Myalgia, muscle weakness, arthralgia, back pain, pain in extremity, muscle spasms, neck pain, musculoskeletal pain Musculoskeletal stiffness, limb discomfort Adult Onset Still’s Disease (AOSD) Renal and urinary disorders Proteinuria, haematuria Nephrolithiasis, ketonuria, nephropathies including anti- GBM disease Reproductive system and breast disorders Menorrhagia, menstruation irregular Cervical dysplasia, amenorrhoea General disorders and administration […]

LEMTRADA is not recommended for patients with inactive disease or those stable on current therapy. Patients treated with LEMTRADA must be given the Package Leaflet, 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 follow-up from treatment initiation until at least 48 months after the last infusion of the second LEMTRADA treatment course.

If an additional course is administered, safety-follow up should be continued until at least 48 months after the last infusion. Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Autoimmunity Treatment may result in the formation of autoantibodies and increase the risk of autoimmune mediated conditions which may be serious and life threatening. g. anti-glomerular basement membrane disease), autoimmune hepatitis (AIH), acquired haemophilia A, thrombotic thrombocytopenic purpura, sarcoidosis, and autoimmune encephalitis.

In the post-marketing setting, patients developing multiple autoimmune disorders after LEMTRADA treatment have been observed. 3). Patients and physicians should be made aware of the potential later onset of autoimmune disorders after the 48 months monitoring period.

Acquired haemophilia A Cases of acquired haemophilia A (anti-factor VIII antibodies) have been reported in both clinical trial and post-marketing setting. Patients typically present with spontaneous subcutaneous haematomas and extensive bruising although haematuria, epistaxis, gastrointestinal or other types of bleeding may occur.

A 5 coagulopathy panel including aPTT must be obtained in all patients that present with such symptoms. In case of a prolonged aPTT patient should be referred to a haematologist. Educate patients on the signs and symptoms of acquired haemophilia A and to seek immediate medical attention, if any of these symptoms are observed.

1. Human Immunodeficiency Virus (HIV) infection. Patients with severe active infection until complete resolution. Patients with uncontrolled hypertension. Patients with a history of arterial dissection of the cervicocephalic arteries. Patients with a history of stroke.

Patients with a history of angina pectoris or myocardial infarction. Patients with known coagulopathy, on anti-platelet or anti-coagulant therapy. Patients with other concomitant autoimmune diseases (besides MS).