Copaxone 20 mg/ml Solution for Injection, Pre-filled syringe

COPAXONE 20 mg/ml is indicated for the treatment of patients who have experienced a well-defined first clinical episode and are determined to be at high risk of developing clinically definite multiple sclerosis (CDMS), (i.e. patients who have had a first clinical episode based on the McDonald criteria and have two or more gadolinium (Gd+) enhancing lesion(s) at 6 mm or more in diameter on MRI scanning). COPAXONE is indicated for the reduction in frequency of relapses in ambulatory (i.e. who can walk unaided) patients with relapsing, remitting multiple sclerosis (MS) characterised by at least two attacks of neurological dysfunction over the preceding two-year period. COPAXONE is not indicated in primary or secondary progressive MS.

Posology: The recommended dosage in adults is 20 mg COPAXONE (one pre-filled syringe), administered as a subcutaneous injection once daily. For single use only. Any unused product or waste material must be discarded. At the present time, it is not known for how long the patient should be treated. A decision concerning the long-term treatment should be made on an individual basis by the treating medical practitioner. Renal impairment: COPAXONE 20 mg/ml has not been specifically studied in patients with renal impairment (see section 4.4). Elderly: COPAXONE 20 mg/ml has not been studied in the elderly. 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 COPAXONE 20 mg/ml subcutaneously every day was similar to that seen in adults. There is not enough information available on the use of COPAXONE 20 mg/ml in children below 12 years of age. Therefore, COPAXONE 20 mg/ml should not be used in this population. Administration: Patients should be instructed on self-injection techniques and should be supervised by a healthcare professional the first time they self-inject and for 30 minutes thereafter. A different site for injection should be chosen every day as this will reduce the chances of any irritation or pain at the site of injection. Sites for self-injection include the abdomen, arms, hips and thighs. Before the patient begins the procedure to self-inject the COPAXONE 20 mg/ml dose, the following points should be noted: The patient should decide where to inject him/herself: There are seven injection areas on the body. Within each injection area there are multiple injection sites (Figure 1). The injection sites within an area should be rotated. Each site should not be used more than once each week. Marking a calendar may help the patient keep track of the sites used each day. The patient should administer the injection consistently, at the same time each day (when the patient feels strongest). The patient may find it beneficial to have a friend attend the injection training as his/her assistant, and to have the friend be present for the first injection. If the injection needs to be delayed, the blister should be returned to the package and stored in the refrigerator. 1. The syringe should be removed from its protective blister by peeling back the paper label. 2. The patient should pick up the pre-filled syringe as he/she would pick up a pencil, using the hand he/she writes with. The plastic cover should be removed from the needle. 3. Advise the patient to pinch a fold of about 5 cm of skin between the thumb and the index finger (Figure 2). 4. The needle should be inserted into the 5 cm fold of skin. Advise the patient that it may help to steady his/her hand by resting the heel of the hand against the body (Figure 3). 5. The fold of skin should be released when the needle is all the way in. 6. Advise the patient to inject the medication by holding the syringe steady while pushing down on the plunger until the syringe is empty. The injection should take just a few seconds.

COPAXONE 20 mg/ml is contraindicated under the following conditions: u2022 Patients known to be hypersensitive to glatiramer acetate or to any of the excipients listed in section 6.1.

COPAXONE 20 mg/ml should only be administered subcutaneously. COPAXONE 20 mg/ml should not be administered by the intravenous or intramuscular route. The initiation of COPAXONE 20 mg/ml treatment should be supervised by a medical practitioner experienced in the treatment of MS. The treating medical practitioner should explain to the patient that a reaction associated with at least one of the following: vasodilatation (flushing), chest pain, dyspnoea, palpitations or tachycardia (see section 4.8), may occur within minutes of a COPAXONE 20 mg/ml injection. The majority of these symptoms are short-lived and resolve spontaneously without any sequelae. Should a severe adverse event occur, the patient must immediately stop COPAXONE 20 mg/ml treatment and contact his/her medical practitioner or any emergency doctor. Symptomatic treatment may be instituted at the discretion of the medical practitioner. There is no evidence to suggest that any particular patient groups are at special risk from these reactions. Nevertheless, caution should be exercised when administering COPAXONE 20 mg/ml 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. Serious hypersensitivity reactions (e.g. bronchospasm, anaphylaxis or urticaria) may occur. If reactions are severe, appropriate treatment should be instituted and COPAXONE 20 mg/ml should be discontinued. Glatiramer acetate-reactive antibodies were detected in patientsu2019 sera during daily chronic treatment with COPAXONE 20 mg/ml. 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 20 mg/ml. In patients with renal impairment, renal function should be monitored while they are treated with COPAXONE 20 mg/ml. Whilst there is no evidence of glomerular deposition of immune complexes in patients, the possibility cannot be excluded. Rare cases of severe liver injury (including hepatitis with jaundice, liver failure, and in isolated cases liver transplantation) have been reported with COPAXONE 20 mg/ml in post-marketing experience (see section 4.8). Liver injury occurred from days to years after initiating treatment with COPAXONE 20 mg/ml. Concomitant conditions reported in these cases included excessive alcohol consumption, existing or history of liver injury and use of other potentially hepatotoxic medicines. In case of clinically significant liver injury, discontinuation of COPAXONE 20 mg/ml should be considered.

Interaction between COPAXONE 20 mg/ml and other medicines have not been formally evaluated. There are no data on interaction with interferon beta. Observations from existing clinical trials and post-marketing experience do not suggest any significant interactions of COPAXONE 20 mg/ml with therapies commonly used in MS patients, including the concurrent use of corticosteroids for up to 28 days. In vitro data 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 20 mg/ml has, theoretically, the potential to affect the distribution of protein bound substances concomitant use of such medicines 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 20 mg/ml. To date, no relevant epidemiological data are available. As a precautionary measure, it is preferable to avoid the use of COPAXONE 20 mg/ml during pregnancy unless the benefit to the mother outweighs the risk to the fetus. 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 breastfeeding or to discontinue/abstain from COPAXONE 20 mg/ml therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

COPAXONE 20 mg/ml may cause syncope and motor dysfunction, and therefore may impair the ability to drive and use machines. However, no studies on the effect on the ability to drive and use machines have been performed.

In clinical trials, injection-site reactions were seen to be the most frequent adverse reactions and were reported by the majority of patients receiving COPAXONE 20 mg/ml. In controlled studies, the proportion of patients reporting these reactions, at least once, was higher following treatment with COPAXONE 20 mg/ml (70 %) than placebo injections (37 %). The most commonly reported injection site reactions, in clinical trials and 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(s) may occur within minutes of a COPAXONE 20 mg/ml injection. At least one component of this Immediate Post-Injection Reaction was reported at least once by 31 % of patients receiving COPAXONE 20 mg/ml compared to 13 % of patients receiving placebo. Adverse reactions identified from clinical trials and post marketing experience 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 20 mg/ml 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 20 mg/ml 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 20 mg/ml and 238 patients treated with placebo for up to 36 months.

A few cases of overdosage with COPAXONE 20 mg/ml (up to 300 mg glatiramer acetate) have been reported. These cases were not associated with any adverse reactions other than those mentioned in section 4.8. In case of overdose, patients should be monitored and the appropriate symptomatic and supportive therapy instituted.