COPAXONE Solution for injection Ref.[8738] Active ingredients: Glatiramer

Copaxone should only be administered subcutaneously. Copaxone should not be administered by intravenous or intramuscular routes.

The treating physician should explain to the patient that a reaction associated with at least one of the following symptoms may occur within minutes of a Copaxone injection: vasodilatation (flushing), chest pain, dyspnoea, palpitations or tachycardia (see section 4.8). 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 Copaxone 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 Copaxone to patients with pre-existing cardiac disorders. These patients should be followed up regularly during treatment.

Convulsions and/or anaphylactoid or allergic reactions have been reported rarely.

Serious hypersensitivity reactions (e.g. bronchospasm, anaphylaxis or urticaria) may rarely occur. If reactions are severe, appropriate treatment should be instituted and Copaxone should be discontinued.

Glatiramer acetate-reactive antibodies were detected in patients' sera during daily chronic treatment with Copaxone. 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 Copaxone.

In patients with renal impairment, renal function should be monitored while they are treated with Copaxone. Whilst there is no evidence of glomerular deposition of immune complexes in patients, the possibility cannot be excluded.

Interaction between Copaxone and other medicinal products have not been formally evaluated.

Observations from existing clinical trials and post-marketing experience do not suggest any significant interactions of Copaxone with therapies commonly used in MS patients, including the concurrent use of corticosteroids for up to 28 days.

In vitro work suggests that glatiramer acetate in blood is highly bound to plasma proteins but that it is not displaced by, and does not itself displace, phenytoin or carbamazepine. Nevertheless, as Copaxone has, theoretically, the potential to affect the distribution of protein-bound substances, concomitant use of such medicinal products should be monitored carefully.

Pregnancy

Studies in animals have not shown reproductive toxicity (see section 5.3).

Current data on pregnant women indicate no malformative or feto/neonatal toxicity of Copaxone. To date, no relevant epidemiological data are available. As a precautionary measure, it is preferable to avoid the use of Copaxone during pregnancy unless the benefit to the mother outweighs the risk to the foetus.

Breastfeeding

It is unknown whether glatiramer acetate or its metabolites are excreted in human milk. In rats, no significant effects on offspring were observed except for a slight reduction in body weight gains in the offspring of mothers dosed during pregnancy and throughout lactation (see section 5.3).

A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Copaxone therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

No studies on the effects on the ability to drive and use machines have been performed.

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 Copaxone. In controlled studies, the proportion of patients reporting these reactions, at least once, was higher following treatment with Copaxone (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.

A reaction, associated with at least one or more of the following symptoms, has been described as the immediate post-injection reaction: vasodilatation (flushing), chest pain, dyspnoea, palpitation or tachycardia (see section 4.4). This reaction may occur within minutes of a Copaxone injection. At least one component of this Immediate Post-Injection Reaction was reported at least once by 31% of patients receiving Copaxone compared to 13% of patients receiving placebo.

All adverse reactions, which were more frequently reported in Copaxone vs. placebo-treated patients, are presented in the table below. This data was derived from four pivotal, double-blind, placebo-controlled clinical trials with a total of 512 patients treated with Copaxone 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 Copaxone 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 Copaxone and 238 patients treated with placebo for up to 36 months.

Very Common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)

Infections and infestations

Very common: Infection, Influenza

Common: Bronchitis, Gastroenteritis, Herpes Simplex, Otitis Media, Rhinitis, Tooth Abscess, Vaginal Candidiasis*

Uncommon: Abscess, Cellulitis, Furuncle, Herpes Zoster, Pyelonephritis

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Common: Benign Neoplasm Of Skin, Neoplasm

Uncommon: Skin Cancer

Blood and lymphatic system disorders

Common: Lymphadenopathy*

Uncommon: Leukocytosis, Leukopenia, Splenomegaly Thrombocytopenia, Lymphocyte Morphology Abnormal

Immune system disorders

Common: Hypersensitivity

Endocrine disorders

Uncommon: Goitre, Hyperthyroidism

Metabolism and nutrition disorders

Common: Anorexia, Weight Increased*

Uncommon: Alcohol Intolerance, Gout, Hyperlipidaemia, Blood Sodium Increased, Serum Ferritin Decreased

Psychiatric disorders

Very common: Anxiety*, Depression

Common: Nervousness

Uncommon: Abnormal Dreams, Confusional State, Euphoric Mood, Hallucination, Hostility, Mania, Personality Disorder, Suicide Attempt

Nervous system disorders

Very common: Headache

Common: Dysgeusia, Hypertonia, Migraine, Speech Disorder, Syncope, Tremor*

Uncommon: 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

Common: Diplopia, Eye Disorder*

Uncommon: Cataract, Corneal Lesion, Dry Eye, Eye Haemorrhage, Eyelid Ptosis, Mydriasis, Optic Atrophy

Ear and labyrinth disorders

Common: Ear Disorder

Cardiac disorders

Common: Palpitations*, Tachycardia*

Uncommon: Extrasystoles, Sinus Bradycardia, Tachycardia Paroxysmal

Vascular disorders

Very common: Vasodilatation*

Uncommon: Varicose Vein

Respiratory, thoracic and mediastinal disorders

Very common: Dyspnoea*

Common: Cough, Rhinitis Seasonal

Uncommon: Apnoea, Epistaxis, Hyperventilation, Laryngospasm, Lung Disorder, Choking Sensation

Gastrointestinal disorders

Very common: Nausea*

Common: Anorectal Disorder, Constipation, Dental Caries, Dyspepsia, Dysphagia, Faecal Incontinence, Vomiting*

Uncommon: Colitis, Colonic Polyp, Enterocolitis, Eructation, Oesophageal Ulcer, Periodontitis Rectal Haemorrhage, Salivary Gland Enlargement

Hepatobiliary disorders

Common: Liver Function Test Abnormal

Uncommon: Cholelithiasis, Hepatomegaly

Skin and subcutaneous tissue disorders

Very common: Rash*

Common: Ecchymosis, Hyperhidrosis, Pruritus, Skin Disorder*, Urticaria

Uncommon: Angioedema, Dermatitis Contact, Erythema Nodosum, Skin Nodule

Musculoskeletal and connective tissue disorders

Very common: Arthralgia, Back Pain*

Common: Neck Pain

Uncommon: Arthritis, Bursitis, Flank Pain, Muscle Atrophy, Osteoarthritis

Renal and urinary disorders

Common: Micturition Urgency, Pollakiuria, Urinary Retention

Uncommon: Haematuria, Nephrolithiasis, Urinary Tract Disorder, Urine Abnormality

Pregnancy, puerperium and perinatal Conditions

Uncommon: Abortion

Reproductive system and breast disorders

Uncommon: Breast Engorgement, Erectile Dysfunction, Pelvic Prolapse, Priapism, Prostatic Disorder, Smear Cervix Abnormal, Testicular Disorder, Vaginal Haemorrhage, Vulvovaginal Disorder

General disorders and administration site conditions

Very common: Asthenia, Chest Pain*, Injection Site Reactions*§, Pain*

Common: Chills*, Face Oedema*, Injection Site Atrophy♣, Local Reaction*, Oedema Peripheral, Oedema, Pyrexia

Uncommon: Cyst, Hangover, Hypothermia, Immediate Post-Injection Reaction, Inflammation, Injection Site Necrosis, Mucous Membrane Disorder

Injury, poisoning and procedural complications

Uncommon: Post Vaccination Syndrome

* More than 2% (>2/100) higher incidence in the Copaxone treatment group than in the placebo group. Adverse reaction without the * symbol represents a difference of less than or equal to 2%.
§ The term ‘Injection site reactions’ (various kinds) comprises all adverse events occurring at the injection site excluding injection site atrophy and injection site necrosis, which are presented separately within the table.
♣ Includes terms which relate to localised lipoatrophy at the injection sites.

In the fourth trial noted above, an open-label treatment phase followed the placebo-controlled period (see section 5.1). No change in the known risk profile of Copaxone was observed during the open-label follow-up period of up to 5 years.

The following adverse reaction reports were collected from MS patients treated with Copaxone in uncontrolled clinical trials and from post-marketing experience with Copaxone: hypersensitivity reactions (including rare occurrence of anaphylaxis, >1/10000, <1/1000.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.