Glairameru acetate-vista

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GLATIRAMER ACETATE-VISTA (GLATIRAMER ACETATE-VISTA)

Composition:

Active substance: glatiramer acetate;

1 ml of injectable solution contains 40 mg of glatiramer acetate;

Excipients: mannite (E 421), water for injections.

*Glatiramer acetate is an acetate salt of synthetic polypeptides containing four naturally occurring amino acids: L-glutamic acid, L-alanine, L-tyrosine, and L-lysine, with molar fractions of 0.129–0.153, 0.392–0.462, 0.086–0.100, and 0.300–0.374, respectively. The average molecular weight of glatiramer acetate is 5000–9000 Da. 40 mg of glatiramer acetate is equivalent to 36 mg of glatiramer base.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless or slightly yellowish/brownish solution in a transparent colorless glass syringe with a needle with cap, plunger, and stopper.

Pharmacotherapeutic group. Antineoplastic and immunomodulating agents, other immunostimulants. ATC code L03AX13.

Pharmacological properties.

Pharmacodynamics.

The mechanisms by which glatiramer acetate exerts its effects in patients with multiple sclerosis (MS) are not fully understood. However, it is believed to act through modification of the immune process thought to be responsible for the pathogenesis of MS. This hypothesis is supported by data from studies investigating the pathogenesis of experimental allergic encephalomyelitis (EAE)—a condition induced in several animal species by immunization with central nervous system tissue containing myelin, commonly used as an experimental animal model of MS. Studies in animals and in patients with MS indicate that administration of glatiramer acetate induces and activates peripherally glatiramer acetate-specific suppressor T-cells.

Relapsing-remitting multiple sclerosis

Data on the efficacy of glatiramer acetate administered as subcutaneous injections at a dose of 40 mg/mL three times per week to reduce relapse frequency were obtained from a 12-month placebo-controlled study. The total number of confirmed relapses was selected as the primary efficacy endpoint. Secondary MRI endpoints measured at months 6 and 12 included the cumulative number of lesions with contrast enhancement on T2-weighted images and the cumulative number of lesions with contrast enhancement on T1-weighted images. A total of 1404 patients were randomized in a 2:1 ratio to receive glatiramer acetate 40 mg/mL (n = 943) or placebo (n = 461). Both treatment groups were comparable with respect to patient status at baseline, clinical disease characteristics, and MRI parameters. Patients had a mean of 2.0 relapses in the 2 years prior to the screening period.

Treatment with glatiramer acetate 40 mg/mL resulted in a 34.4% reduction in the total number of relapses (p < 0.0001), with a relative risk of 0.656 and a 95% confidence interval (CI) [0.539–0.799].

Significant and statistically significant changes in primary and secondary efficacy endpoints were observed with glatiramer acetate 40 mg/mL, consistent with the efficacy of treatment with glatiramer acetate 20 mg/mL once daily. The table below presents the values of primary and secondary efficacy endpoints in the randomized patient group.

*Absolute risk reduction was defined as the difference between the adjusted number of confirmed relapses over 12 months with glatiramer acetate 40 mg/mL administered three times weekly and the adjusted number of confirmed relapses over 12 months with placebo.

**Relative risk was defined as the ratio of the adjusted mean risk with glatiramer acetate 40 mg/mL administered three times weekly to the adjusted mean risk with placebo.

A direct comparison of safety between glatiramer acetate 20 mg/mL administered once daily and glatiramer acetate 40 mg/mL administered three times weekly has not been conducted within a single study.

In this 12-month study, there was no evidence that treatment with glatiramer acetate 40 mg/mL administered three times weekly affects the progression of disability or the duration of relapses. Currently, there are no data on the use of glatiramer acetate in patients with primary or secondary progressive disease.

Pharmacokinetics.

Pharmacokinetic studies have not been conducted in patients. In vitro data and limited data from studies in healthy volunteers indicate that following subcutaneous administration of glatiramer acetate, the active substance is readily absorbed, and a large portion of the dose is rapidly broken down into smaller fragments within the subcutaneous tissue.

Clinical characteristics.

Indications.

The medicinal product Glatiramer Acetate-Vista, 40 mg/mL, is indicated for the treatment of relapsing forms of multiple sclerosis.

Glatiramer Acetate-Vista is not prescribed for primary or secondary progressive multiple sclerosis.

Contraindications.

Hypersensitivity to the active substance (glatiramer acetate) or to any of the excipients of the medicinal product.

Safety precautions.

The medicinal product is intended for single use only. Unused medicinal product or waste material must be destroyed.

Interaction with other medicinal products and other types of interactions.

Interaction between glatiramer acetate and other medicinal products has been insufficiently studied.

There are no data regarding interaction with beta-interferon.

An increased frequency of injection site reactions with glatiramer acetate has been observed. An increased frequency of local reactions has been reported in patients receiving concomitant corticosteroid therapy.

In vitro studies indicate that glatiramer acetate in blood binds to plasma proteins, but it does not displace and is not displaced by phenytoin or carbamazepine. However, since glatiramer acetate theoretically has the potential to affect the distribution of protein-bound substances, concomitant use of such medicinal products should be carefully monitored.

Special precautions for use.

The medicinal product Glatiramer Acetate-Vista can only be administered as subcutaneous injections. The drug must not be used as intravenous or intramuscular injections.

Initiation of therapy with this drug should be under the supervision of a neurologist or a physician experienced in the treatment of multiple sclerosis. Glatiramer acetate may cause injection-site reactions as well as anaphylactic reactions.

Post-injection reactions

The treating physician must inform the patient that a reaction associated with at least one of the following symptoms—vasodilation (flushing), chest pain, dyspnea, palpitations, or tachycardia—may occur within minutes after injection of Glatiramer Acetate-Vista, 40 mg/mL. Most of these symptoms are short-lived and resolve spontaneously without consequences. In the event of a serious adverse reaction, the patient must immediately discontinue the drug and seek medical attention. Symptomatic treatment may be considered if necessary. There is no evidence of an increased risk of these adverse reactions in any specific patient group. Nevertheless, caution should be exercised when administering the drug to patients with a history of cardiac disorders. Such patients should be monitored regularly during treatment.

Anaphylactic reactions

Anaphylactic reactions may occur shortly after administration of glatiramer acetate, or even several months or years after initiation of treatment.

Fatal cases have been reported. Some symptoms of anaphylactic reactions may overlap with post-injection reactions.

All patients receiving glatiramer acetate therapy and their caregivers should be informed about the signs and symptoms of anaphylactic reactions and instructed to seek immediate emergency medical help if such symptoms occur (see section "Adverse reactions").

If an anaphylactic reaction occurs, treatment with glatiramer acetate must be discontinued.

Glatiramer acetate-reactive antibodies have been detected in the serum of patients during daily continuous therapy with Glatiramer Acetate-Vista, 40 mg/mL. Peak levels were reached on average after 3–4 months of treatment, after which levels declined and stabilized at a level slightly above baseline. There is no evidence that these glatiramer acetate-reactive antibodies are neutralizing or that their formation affects the clinical efficacy of Glatiramer Acetate-Vista.

Renal function should be monitored in patients with renal impairment during treatment with this medicinal product. Although there is no evidence of glomerular deposition of immune complexes, this possibility cannot be excluded. During the post-marketing use of glatiramer acetate, rare cases of severe liver injury have been reported, including hepatitis with jaundice, hepatic failure, and in some cases, liver transplantation (see section "Adverse reactions"). Liver injury occurred from several days to several years after initiation of glatiramer acetate treatment. In most cases, severe liver injury resolved upon discontinuation of treatment. In some cases, these reactions occurred in the presence of excessive alcohol consumption, pre-existing or past liver disease, or concomitant use of other potentially hepatotoxic medicinal products. Patients should be regularly monitored for signs of liver injury and should seek immediate medical attention if symptoms of liver injury occur. In cases of clinically significant liver injury, discontinuation of glatiramer acetate should be considered.

Use during pregnancy or breastfeeding.

Pregnancy. A certain amount of data in pregnant women (300–1000 pregnancy cases) indicates no fetotoxic/neonatal toxicity or developmental abnormalities of the fetus. Animal studies have not revealed reproductive toxicity. If necessary, the use of Glatiramer Acetate-Vista during pregnancy may be considered.

Breastfeeding. Due to the physicochemical properties and low oral absorption of the drug, the impact of glatiramer acetate on newborns/infants via breast milk is expected to be negligible. Data from a non-interventional retrospective study involving 60 infants breastfed by mothers receiving glatiramer acetate, compared to 60 infants whose mothers received no disease-modifying therapy, as well as some post-marketing data, suggest no negative impact of glatiramer acetate. Glatiramer Acetate-Vista may be used during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

The ability to affect reaction speed when driving or operating machinery has not been studied.

Method of Administration and Dosage

Initiation of therapy with the medicinal product Glatiramer Acetate-Vista should be carried out under the supervision of a neurologist or a physician experienced in the treatment of multiple sclerosis. The recommended dose for adults is 40 mg of glatiramer acetate (one pre-filled syringe), administered subcutaneously three times per week. The interval between injections should be at least 48 hours. It is recommended to use the medication on the same days each week.

The long-term duration of treatment with this medicinal product has not yet been established. The decision regarding the duration of therapy is made by the physician on an individual basis.

Elderly patients. The use of the medicinal product in elderly patients has not been specifically studied.

Patients with renal impairment. Specific studies on the use of the medicinal product in patients with impaired renal function have not been conducted.

Patients should be provided with instructions on the technique of self-administration and be supervised by a physician during the first self-injection and for 30 consecutive minutes thereafter.

To reduce the likelihood of irritation or pain at the injection site, each subsequent injection should be administered at a different location. The medicinal product may be injected into the abdomen, arms, thighs, and buttocks.

General recommendations for use:

When administering the medicinal product, it is important to follow the rules listed below:

• administer the product only subcutaneously;
• use the dose prescribed by the physician;
• use each syringe for injection only once; unused medication or leftovers must be discarded;
• do not mix or administer Glatiramer Acetate-Vista 40 mg/mL simultaneously with other medicinal products;
• do not use the pre-filled syringe if particulate matter is present in the solution; in such a case, take another package.

Instructions for use:

1. Before administering the medicinal product, ensure that all necessary items for injection are available:

   • one blister pack of Glatiramer Acetate-Vista 40 mg/mL containing a pre-filled syringe;
   • a disposal container for used syringes and needles.

2. Take one blister pack containing the pre-filled syringe from the outer packaging. All unused syringes must be stored in their original packaging.

3. If the medicinal product has been stored in the refrigerator, allow the blister pack with the pre-filled syringe to sit at room temperature for at least 20 minutes to ensure it reaches room temperature.

4. Before administering the medicinal product, wash hands thoroughly with soap and water.

5. Select an injection site. Figure 1 indicates seven possible injection sites on the body: arms, thighs, buttocks, and abdomen (excluding the area around the navel). Each injection area contains multiple injection points. Always use a different injection point to reduce the likelihood of irritation or pain at the injection site. Rotate injection sites within each specific area consistently. Do not administer injections into the same location repeatedly.

Do not use painful areas, discolored skin, or areas with induration or nodules for injection.

It is recommended to plan a rotation schedule for injection sites and record the corresponding entries in an injection diary.

Some body areas may be inconvenient for self-injection (e.g., arms). In such cases, assistance from another person may be required.

V – top; M – middle; L – bottom.

Fig. 1

1. Remove the syringe from its protective blister packaging by removing the paper label.
2. Hold the syringe in the hand used for writing, like a pencil. Remove the protective needle cap.
3. Gently pinch the skin into a fold using the thumb and index finger (Fig. 2).
4. Insert the needle into the skin (Fig. 3). Administer the drug by steadily pressing down on the syringe plunger until it is completely emptied.

Fig. 2 \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ 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\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \

Adverse Reactions

The majority of safety data on glatiramer acetate are based on the experience of subcutaneous administration of glatiramer acetate (20 mg/mL) once daily. The safety data for glatiramer acetate presented below were obtained from four placebo-controlled studies of glatiramer acetate (20 mg/mL) administered once daily and one placebo-controlled study of glatiramer acetate (40 mg/mL) administered three times per week. A direct comparison of safety between glatiramer acetate (20 mg/mL) once daily and glatiramer acetate (40 mg/mL) three times per week has not been conducted in a single study.

Glatiramer acetate (20 mg/mL) once daily.

In all clinical studies, the most common adverse reactions with glatiramer acetate (20 mg/mL) were injection site reactions, observed in the majority of patients receiving the drug. In controlled studies, the proportion of patients experiencing these reactions at least once was higher with glatiramer acetate (20 mg/mL) (70%) than with placebo injections (37%). Injection site reactions most commonly observed with glatiramer acetate (20 mg/mL) compared to placebo included erythema, pain, nodules, pruritus, swelling, inflammation, and hypersensitivity.

A reaction associated with at least one of the following symptoms—vasodilation (flushing), chest pain, dyspnea, palpitations, or tachycardia—was described as an immediate post-injection reaction. This reaction may occur within minutes after injection of glatiramer acetate. At least one symptom of immediate post-injection reaction (individual symptoms of immediate post-injection reaction with specified frequencies are listed below) was observed in 31% of patients receiving glatiramer acetate (20 mg/mL), compared to 13% of patients receiving placebo.

All adverse reactions identified during clinical trials and in the post-marketing period are listed below. Clinical trial data were derived from four double-blind, placebo-controlled clinical studies involving a total of 512 patients treated with glatiramer acetate and 509 patients treated with placebo for up to 36 months. Three studies included patients with relapsing-remitting MS, enrolling a total of 269 patients receiving glatiramer acetate (20 mg daily) and 271 patients in the placebo group over 35 months. The fourth clinical study included patients with a first clinical episode identified as being at high risk for developing clinically definite MS. In this study, 243 patients received glatiramer acetate (20 mg daily) and 238 patients received placebo for 36 months.

The adverse reactions listed below are classified by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100).

Infections and infestations.

Very common: infections, influenza.

Common: bronchitis, gastroenteritis, herpes simplex, otitis media, rhinitis, dental abscess, vaginal candidiasis*.

Uncommon: abscess, cellulitis, furunculosis, herpes zoster, pyelonephritis.

Benign, malignant and unspecified neoplasms (including cysts and polyps).

Common: benign skin tumors, neoplasms.

Uncommon: skin cancer.

Blood and lymphatic system disorders.

Common: lymphadenopathy*.

Uncommon: leukocytosis, leukopenia, splenomegaly, thrombocytopenia, abnormal lymphocyte morphology.

Immune system disorders.

Common: hypersensitivity.

Uncommon: anaphylactic reactions.

Endocrine disorders.

Uncommon: goiter, hyperthyroidism.

Metabolism and nutrition disorders.

Common: anorexia, weight gain*.

Uncommon: alcohol intolerance, gout, hyperlipidemia, increased blood sodium levels, decreased plasma ferritin.

Psychiatric disorders.

Very common: anxiety*, depression.

Common: restlessness.

Uncommon: abnormal dreams, confusion, euphoria, hallucinations, 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, convulsions, dysgraphia, dyslexia, dystonia, motor dysfunction, myoclonus, neuritis, neuromuscular blockade, nystagmus, paralysis, peroneal nerve paralysis, stupor, visual field defect.

Eye disorders.

Common: diplopia, eye disorders*.

Uncommon: cataract, corneal lesion, dry eyes, eye hemorrhage, ptosis of upper eyelid, mydriasis, optic atrophy.

Ear and labyrinth disorders.

Common: ear disorders.

Cardiac disorders.

Very common: vasodilation*.

Common: palpitations*, tachycardia*.

Uncommon: extrasystoles, sinus bradycardia, paroxysmal tachycardia, varicose veins.

Respiratory, thoracic and mediastinal disorders.

Very common: dyspnea*.

Common: cough, seasonal rhinitis.

Uncommon: apnea, epistaxis, hyperventilation, laryngospasm, lung disease, suffocation sensation.

Gastrointestinal disorders.

Very common: nausea*.

Common: anorectal disorders, constipation, dental caries, dyspepsia, dysphagia, fecal incontinence, vomiting*.

Uncommon: colitis, intestinal polyp, enterocolitis, eructation, esophageal ulcer, periodontitis, rectal bleeding, salivary gland enlargement.

Hepatobiliary disorders.

Common: liver function test abnormalities.

Uncommon: cholelithiasis, liver injury, hepatomegaly.

Rare: toxic hepatitis, liver injury.

Frequency not known: liver failure****.

Skin and subcutaneous tissue disorders.

Very common: rash*.

Common: ecchymosis, hyperhidrosis, pruritus, skin disorders*, urticaria.

Uncommon: angioedema, contact dermatitis, erythema nodosum, skin nodules.

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: urinary urgency, pollakiuria, urinary retention.

Uncommon: hematuria, nephrolithiasis, urinary tract disorders, abnormal urinalysis.

Reproductive system and breast disorders.

Uncommon: breast engorgement, erectile dysfunction, pelvic organ prolapse, priapism, prostate disorders, abnormal cervical smear, testicular disorders, vaginal bleeding, vulvovaginal disorders.

General disorders and administration site conditions.

Very common: asthenia, chest pain*, injection site reactions*^, pain*.

Common: chills*, facial swelling*, atrophy at injection site◊, local reaction*, peripheral edema, swelling, hyperthermia.

Uncommon: cyst, hangover syndrome, hypothermia, immediate post-injection reaction, inflammation, necrosis at injection site, mucosal disorders.

Injury, poisoning and procedural complications.

Uncommon: post-vaccination syndrome.

*Number of cases was greater than 2% (> 2/100) in the glatiramer acetate group compared to the placebo group. Adverse reactions without the * symbol indicate a difference of less than 2% or equal to 2%.

^The term "injection site reactions" (various types) includes all adverse reactions occurring at the injection site, except for atrophy at injection site and necrosis at injection site, which are listed separately.

◊Includes terms related to localized lipodystrophy at the injection site.

****Several cases of liver transplantation have been reported.

Description of selected adverse reactions

In the fourth study mentioned above, an open-label treatment phase followed the placebo-controlled period. No changes in the known safety profile of glatiramer acetate (20 mg/mL) were observed during the subsequent open-label 5-year study.

Glatiramer acetate (40 mg/mL), administered three times per week. The safety of glatiramer acetate (40 mg/mL) was evaluated in a double-blind, placebo-controlled study involving patients with relapsing-remitting multiple sclerosis. During the study, 943 patients received glatiramer acetate (40 mg/mL) three times per week, and 461 patients received placebo for 12 months. Overall, patients receiving glatiramer acetate (40 mg/mL) (three times per week) experienced the same types of adverse reactions at similar frequencies as those observed with glatiramer acetate (20 mg/mL) (daily).

Specifically, injection site reactions and immediate post-injection reactions occurred less frequently in patients receiving glatiramer acetate (40 mg/mL) (three times per week) compared to those receiving glatiramer acetate (20 mg/mL) (daily) (35.5% vs. 70% for injection site reactions and 7.8% vs. 31% for immediate post-injection reactions, respectively).

Injection site reactions were observed in 36% of patients receiving glatiramer acetate (40 mg/mL), compared to 5% of placebo recipients. Immediate post-injection reactions occurred in 8% of patients receiving glatiramer acetate (40 mg/mL), compared to 2% of those receiving placebo. Several specific adverse reactions were reported:

• Anaphylactic reactions may occur shortly after administration of glatiramer acetate or even several months or years after initiation of treatment (see section "Special precautions").
• No reports of necrosis at the injection site have been recorded.
• Skin erythema and limb pain, not observed with glatiramer acetate (20 mg/mL), occurred in 2.1% of patients receiving glatiramer acetate (40 mg/mL) (common: ≥ 1/100 to < 1/10).
• Drug-induced liver injury and toxic hepatitis were observed with glatiramer acetate (40 mg/mL), each reported in one patient (0.1%) (uncommon: ≥ 1/1000 to < 1/100).

In uncontrolled clinical studies and during post-marketing use, hypersensitivity reactions (including rare cases of anaphylactoid reactions (≥ 1/10,000 to < 1/1,000)) and elevated liver enzymes without clinically significant consequences have also been reported in patients with MS receiving glatiramer acetate.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after drug authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua

Shelf life. 3 years.

Storage conditions.

Store in the original packaging to protect from light at 2–8 °C (in the refrigerator). Do not freeze. Keep out of reach of children. If it is not possible to store prefilled syringes in the refrigerator, they may be stored at 15–25 °C for up to 1 month.

If prefilled syringes containing solution remain unused after this one-month period and are still in the original packaging, they must be stored in the refrigerator at 2–8 °C.

Incompatibilities.

The medicinal product should not be mixed with other medicinal products, as compatibility studies have not been conducted.

Packaging. 1 mL of solution in a pre-filled syringe; 1 syringe per blister pack; 12 syringes per cardboard box.

Prescription status. Prescription only.

Manufacturers.

Sicor España, S.L.

Sicor B.V.

Manufacturer locations and addresses of places of business.

C/ Castello, n° 1, Sant Boi de Llobregat, Barcelona, 08830, Spain.

Mijlweg 22, Nijmegen, 6545 SM, The Netherlands.