BRABIO

The initiation of glatiramer acetate treatment should be supervised by a neurologist or a physician experienced in the treatment of MS. Posology The recommended dosage in adults is 20 mg of glatiramer acetate (one pre- filled syringe), administered as a subcutaneous injection once daily.

At the present time, it is not known for how long the patient should be treated. A decision concerning long term treatment should be made on an individual basis by the treating physician. Paediatric population The safety and efficacy of glatiramer acetate in children and adolescents has not been established.

However, limited published data suggest that the safety profile in adolescents from 12 to 18 years of age receiving glatiramer acetate 20mg subcutaneously every day is similar to that seen in adults. There is not enough information available on the use of glatiramer acetate in children below 12 years of age to make any recommendation for its use.

Therefore, glatiramer acetate should not be used in this population. Special populations Elderly Glatiramer acetate has not been specifically studied in the elderly. 4). Method of administration Glatiramer acetate is for subcutaneous use.

Patients should be instructed in self-injection techniques and should be supervised by a health-care professional the first time they self-inject and for 30 minutes after. A different site should be chosen for every injection, so this will reduce the chances of any irritation or pain at the site of the injection.

Sites for self- injection include the abdomen, arms, hips and thighs. The MyJECT device is available should the patients want to make their injection with an injection device. The MyJECT device is an autoinjector to be used with Brabio 20 mg/mL Solution for Injection pre-filled syringes and it has not been tested with other pre-filled syringes.

The MyJECT device should be used as recommended in the information provided by the device manufacturer.

In all clinical trials, injection-site reactions were seen to be the most frequent adverse reactions and were reported by the majority of patients receiving glatiramer acetate. In controlled studies, the proportion of patients reporting these reactions, at least once, was higher following treatment with glatiramer acetate (70%) than placebo injections (37%).

The most commonly reported injection-site reactions, in clinical trials and in post-marketing experience, were erythema, pain, mass, pruritus, oedema, inflammation, hypersensitivity and rare occurrences of lipoatrophy and skin necrosis.

4). This reaction may occur within minutes of a glatiramer acetate injection. At least one component of this Immediate Post-Injection Reaction was reported at least once by 31% of patients receiving glatiramer acetate compared to 13% of patients receiving placebo.

Adverse reactions identified from clinical trials and post marketing experience, are presented in the table below. Data from clinical trials was derived from four pivotal, double-blind, placebo-controlled clinical trials with a total of 512 patients treated with glatiramer acetate and 509 patients treated with placebo for up to 36 months.

Three trials in relapsing-remitting MS (RRMS) included a total of 269 patients treated with glatiramer acetate and 271 patients treated with placebo for up to 35 months. The fourth trial in patients who have experienced a first clinical episode and were determined to be at high risk of developing clinically definite MS included 243 patients treated with glatiramer acetate and 238 patients treated with placebo for up to 36 months.

System Organ Class (SOC) 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) “not known” (cannot be estimated from the available data) Infections And Infestations Infection, Influenza Bronchitis, Gastroenteritis, Herpes Simplex, Otitis Media, Rhinitis, Tooth Abscess, Vaginal Candidiasis* Abscess, Cellulitis, Furuncle, Herpes Zoster, Pyelonephritis Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps) Benign Neoplasm Of Skin, Neoplasm Skin Cancer Blood And Lymphatic System Disorders Lymphadenopathy* Leukocytosis, Leukopenia, Splenomegaly, Thrombocytopenia, Lymphocyte Morphology Abnormal Immune System Disorders Hypersensitivity Anaphylactic reaction Endocrine Disorders Goitre, Hyperthyroidism Metabolism And Nutrition Disorders Anorexia, Weight Increased* Alcohol Intolerance, Gout, Hyperlipidaemia, Blood Sodium Increased, Serum Ferritin Decreased Psychiatric Disorders Anxiety*, Depression Nervousness Abnormal Dreams, Confusional State, Euphoric Mood, Hallucination, Hostility, Mania, Personality Disorder, Suicide Attempt Nervous System Disorders Headache Dysgeusia, Hypertonia, Migraine, Speech Disorder, Syncope, Tremor* Carpal Tunnel Syndrome, Cognitive Disorder, Convulsion, Dysgraphia, Dyslexia, Dystonia, Motor Dysfunction, Myoclonus, Neuritis, Neuromuscular Blockade, Nystagmus, Paralysis, Peroneal Nerve Palsy, Stupor, Visual Field Defect Eye Disorders Diplopia, Eye Disorder* Cataract, Corneal Lesion, Dry Eye, Eye Haemorrhage, Eyelid Ptosis, Mydriasis, Optic Atrophy Ear And Labyrinth Disorders Ear Disorder Cardiac Disorders Palpitations*, Tachycardia* Extrasystoles, Sinus Bradycardia, Tachycardia Paroxysmal Vascular Disorders Vasodilatation* Varicose Vein Respiratory, Thoracic And Mediastinal Disorders Dyspnoea* Cough, Rhinitis Seasonal Apnoea, Epistaxis, Hyperventilation, Laryngospasm, Lung Disorder, Choking Sensation Gastrointestinal Disorders Nausea* Anorectal Disorder, Constipation, Dental Caries, Dyspepsia, Dysphagia, Faecal Incontinence, Vomiting* Colitis, Colonic Polyp, Enterocolitis, Eructation, Oesophageal Ulcer, Periodontitis, Rectal Haemorrhage, Salivary Gland Enlargement Hepatobiliary Disorders Liver Function Test Abnormal Cholelithiasis, Hepatomegaly Toxic hepatitis, Liver injury Hepatic failure** Skin And Subcutaneous Tissue Disorders Rash* Ecchymosis, Hyperhidrosis, Pruritus, Skin Disorder*, Urticaria Angioedema, Dermatitis Contact, Erythema Nodosum, Skin Nodule Musculoskeletal And Connective Tissue Disorders Arthralgia, Back Pain* Neck Pain Arthritis, Bursitis, Flank Pain, Muscle Atrophy, Osteoarthritis Renal And Urinary Disorders Micturition Urgency, Pollakiuria, Urinary Retention Haematuria, Nephrolithiasis, Urinary Tract Disorder, Urine Abnormality Pregnancy, Puerperium And Perinatal Conditions Abortion Reproductive System And Breast Disorders Breast Engorgement, Erectile Dysfunction, Pelvic Prolapse, Priapism, Prostatic Disorder, Smear Cervix Abnormal, Testicular Disorder, Vaginal Haemorrhage, Vulvovaginal Disorder General Disorders And Administration Site Conditions Asthenia, Chest Pain*, Injection Site Reactions*§, Pain* Chills*, Face Oedema*, Injection Site Atrophy♣ , Local Reaction*, Oedema Peripheral, Oedema, Pyrexia Cyst, Hangover, Hypothermia, Immediate Post- Injection Reaction, Inflammation, Injection Site Necrosis, Mucous Membrane Disorder Injury, Poisoning And Procedural Complications Post Vaccination Syndrome * More than 2% (>2/100) higher incidence in the glatiramer acetate treatment group than in the placebo group.

Glatiramer acetate should only be administered subcutaneously. Glatiramer acetate should not be administered by intravenous or intramuscular routes. 8). The majority of these symptoms is short-lived and resolves spontaneously without any sequelae.

Should a severe adverse event occur, the patient must immediately stop glatiramer acetate treatment and contact his/her physician or any emergency doctor. Symptomatic treatment may be instituted at the discretion of the physician. There is no evidence to suggest that any particular patient groups are at special risk for these reactions.

Nevertheless, caution should be exercised when administering glatiramer acetate to patients with pre-existing cardiac disorders. These patients should be followed up regularly during treatment. 8). Cases with fatal outcome have been reported.

Some signs and symptoms of anaphylactic reactions may overlap with post-injection reactions. 8). 3). Glatiramer acetate-reactive antibodies were detected in patients' sera during daily chronic treatment with glatiramer acetate. Maximal levels were attained after an average treatment duration of 3-4 months and, thereafter, declined and stabilised at a level slightly higher than baseline.

There is no evidence to suggest that these glatiramer acetate-reactive antibodies are neutralising or that their formation is likely to affect the clinical efficacy of glatiramer acetate. In patients with renal impairment, renal function should be monitored while they are treated with glatiramer acetate.

Whilst there is no evidence of glomerular deposition of immune complexes in patients, the possibility cannot be excluded. Rare cases of severe liver injury have been observed (including hepatitis with jaundice, liver failure, and in isolated cases liver transplantation).

Liver injury occurred from days to years after initiating treatment with Glatiramer acetate. Most instances of severe liver injury resolved with discontinuation of treatment. In some cases, these reactions have occurred in the presence of excessive alcohol consumption, existing or history of liver injury and use of other potentially hepatotoxic medication.

1.