Copaxone Adverse Reactions

This section presents accumulated safety data from four placebo-controlled trials with glatiramer acetate 20 mg/ml administered once daily, and from one placebo-controlled trial with glatiramer acetate 40 mg/ml administered three times a week.
A direct comparison of the safety between glatiramer acetate 20 mg/ml (administered daily) and 40 mg/ml (administered three times per week) in the same study has not been performed.
Glatiramer acetate 20 mg/ml (administered once daily): In all clinical trials with glatiramer acetate 20 mg/ml, 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 20 mg/ml (70%) than placebo injections (37%). The most commonly reported injection-site reactions, which were more frequently reported in glatiramer acetate 20 mg/ml vs. placebo-treated patients, were erythema, pain, mass, pruritus, oedema, inflammation and hypersensitivity.
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 Precautions). 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 20 mg/ml compared to 13% of patients receiving placebo.
All adverse reactions, which were more frequently reported in glatiramer acetate 20 mg/ml vs. placebo-treated patients, are presented in the table as follows. This data was derived from four pivotal, double-blind, placebo-controlled clinical trials with a total 512 patients treated with glatiramer acetate 20 mg/day 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 20 mg/day 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 20mg/day and 238 patients treated with placebo for up to 36 months. (See Table 2.)

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In the fourth trial noted as previously mentioned, an open-label treatment phase followed the placebo-controlled period. No change in the known risk profile of glatiramer acetate 20 mg/ml was observed during the open-label follow-up period of up to 5 years.
Rare (≥1/10,000 to <1/1,000) reports of anaphylactoid reactions were collected from MS patients treated with glatiramer acetate in uncontrolled clinical trials and from post-marketing experience with glatiramer acetate.
Glatiramer acetate 40 mg/ml (administered three times per week): The safety of glatiramer acetate 40 mg/ml was assessed based on a double-blind, placebo-controlled clinical trial in RRMS patients with a total of 943 patients treated with glatiramer acetate 40 mg/ml three times per week, and 461 patients treated with placebo for 12 months.
In general, the kind of adverse drug reactions seen in patients treated with glatiramer acetate 40 mg/ml administered three times per week were those already known and labelled for glatiramer acetate 20 mg/ml administered daily. In particular, adverse injection site reactions (ISR) and immediate post-injection reactions (IPIR) were reported at lower frequency for glatiramer acetate 40 mg/ml administered three times per week than for glatiramer acetate 20 mg/ml administered daily (35.5% vs. 70% for ISRs and 7.8% vs. 31% for IPIRs, respectively).
Injection site reactions were reported by 36% of the patients on glatiramer acetate 40 mg/ml compared to 5% on placebo. Immediate post-injection reaction was reported by 8% of the patients on glatiramer acetate 40 mg/ml compared to 2% on placebo.
A few specific adverse reactions are noted: Anaphylactic response was seen rarely (≥1/10,000, <1/1,000) in MS patients treated with glatiramer acetate 20 mg/ml in uncontrolled clinical trials and from post-marketing experience. It was reported by 0.3% of the patients on glatiramer acetate 40 mg/ml (Uncommon: ≥ 1/1,000 to < 1/100).
No injection site necrosis was reported.
Skin erythema and pain in extremity, not labelled for glatiramer acetate 20 mg/ml, were reported each by 2.1% of the patients on glatiramer acetate 40 mg/ml (Common: ≥ 1/100 to < 1/10).
Drug-induced liver injury and toxic hepatitis, also seen rarely in MS patients treated with glatiramer acetate 20 mg/ml in post marketing surveillance, were each reported by one patient (0.1%) on glatiramer acetate 40 mg/ml (Uncommon: ≥ 1/1,000 to < 1/100).