Copaxone^®-Teva (Solution) Instructions for Use

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

Contact Information

TEVA (Israel)

ATC Code

L03AX13 (Glatiramer acetate)

Active Substance

Glatiramer acetate

Dosage Form

Copaxone®-Teva

Subcutaneous injection solution 20 mg/1 ml: syringes 28 pcs.

Dosage Form, Packaging, and Composition

Solution for subcutaneous injection from colorless to slightly yellow, slightly opalescent.

Excipients: mannitol, water for injections.

1 ml – syringes (1) – blister packs (28) – cardboard boxes.

Clinical-Pharmacological Group

Immunomodulator. A drug used for multiple sclerosis

Pharmacotherapeutic Group

Immunostimulants; other immunostimulants

Pharmacological Action

Immunomodulatory drug. Glatiramer acetate is the acetate salt of synthetic polypeptides formed by 4 natural amino acids: L-glutamic acid, L-alanine, L-tyrosine, and L-lysine and has structural similarities to myelin basic protein.

It has immunomodulatory properties and the ability to block myelin-specific autoimmune reactions that underlie the pathogenesis of destruction of the myelin sheath of nerve conductors in the central nervous system in multiple sclerosis.

Glatiramer acetate has a specific mechanism of action, which is based on its ability to competitively replace myelin antigens – myelin basic protein, myelin oligodendrocyte glycoprotein, and proteolipid protein at the binding sites with molecules of the major histocompatibility complex class II located on antigen-presenting cells.

The consequence of competitive displacement is two reactions: stimulation of antigen-specific suppressor T-lymphocytes (Th2 type) and inhibition of antigen-specific effector T-lymphocytes (Th1 type). Activated T-suppressor lymphocytes enter the systemic circulation and penetrate the central nervous system. Entering the site of inflammation in the central nervous system, these T-lymphocytes are reactivated by myelin antigens, which leads to their production of anti-inflammatory cytokines (including IL-4, IL-6, IL-10), which reduce local inflammation by suppressing the local inflammatory T-cell response. This leads to the accumulation of specific anti-inflammatory Th₂ type cells and inhibition of the pro-inflammatory Th₁ cell system.

In addition, the drug has a neuroprotective effect: it stimulates the synthesis of neurotrophic factor by Th₂ type cells and protects brain structures from damage.

Copaxone^®-Teva does not have a generalized effect on the main links of the body’s normal immune reactions, which fundamentally distinguishes it from non-specific immunomodulators, including beta-interferon drugs.

The antibodies formed to glatiramer acetate do not have a neutralizing effect that reduces the clinical effect of the drug.

Pharmacokinetics

Due to the peculiarities of the chemical structure of glatiramer acetate, which is a mixture of polypeptides formed by natural amino acids, as well as the low therapeutic dose, pharmacokinetic data are only of approximate value. Based on them, as well as on experimental data, it is believed that after subcutaneous administration, the drug is rapidly hydrolyzed at the injection site. Hydrolysis products, as well as a small part of unchanged glatiramer acetate, can enter the lymphatic system and partially reach the vascular bed. Glatiramer acetate exerts its immunomodulatory action at the injection site. The therapeutic effect is mediated through the systemic spread of activated T-suppressor cells. The determined concentration of glatiramer acetate or its metabolites in the blood does not correlate with the therapeutic effect.

Indications

• Relapsing-remitting multiple sclerosis (to reduce the frequency of exacerbations and slow the development of disabling complications).

ICD codes

Dosage Regimen

The drug is prescribed to adults daily subcutaneously at a dose of 20 mg (1 pre-filled syringe for injection) once a day, preferably at the same time, for a long period.

Copaxone^®-Teva should not be administered intravenously or intramuscularly.

Injection rules

The blister with the pre-filled syringe after storage in the refrigerator should be kept at room temperature for at least 20 minutes.

The solution is administered subcutaneously (observing the rules of asepsis and antisepsis) in the area of the forearm, abdomen (stomach area), buttock, or thigh, changing the injection sites daily.

Do not inject into painful points, discolored, reddened areas of the skin, or areas with indurations and nodules. The injection points within the injection area should be constantly changed.

It is recommended to draw up a scheme for changing injection sites and keep it with you. Assistance from another person may be required to perform the injection.

If there are undissolved particles or a change in color, the drug solution is not suitable for use.

Each syringe containing the drug solution is intended for single use only; the remaining drug solution should be destroyed.

The solution contained in the syringe should not be mixed or administered concurrently with any other drug.

When self-administering the drug in case of a missed injection, the patient should administer it immediately as soon as they remember. A double dose of the drug should not be administered. The next injection should be administered only after 24 hours.

Do not stop using Copaxone^®-Teva without consulting a doctor.

Drug administration

1. Remove the syringe from the individual blister pack by removing the paper marking (strip).
2. Take the syringe in your writing hand. Remove the protective cap from the needle.
3. After pre-treating the injection site locally with an alcohol wipe, gently pinch the skin into a fold with your thumb and forefinger.
4. Holding the syringe perpendicular to the injection site, insert the needle into the skin at a 90° angle, administer the drug by pressing the syringe plunger down evenly until the end (until it is completely empty).
5. Remove the syringe with the needle with a vertical upward movement, maintaining the same angle of inclination.
6. Place the syringe in a disposal container.

Adverse Reactions

Immediately after injection the following are possible

Local reactions pain, redness, swelling; rarely – skin or subcutaneous tissue atrophy at the injection site, abscess, hematoma.

Systemic reactions flushing, chest pain, palpitations, anxiety, shortness of breath, difficulty swallowing, urticaria. These symptoms may be temporary and limited and do not require special intervention; they may begin several months after the start of therapy, the patient may experience one or another symptom episodically.

Sometimes the following may be observed

From the cardiovascular system palpitations, vasodilation; rarely – syncope, increased blood pressure, extrasystole, pallor, varicose veins.

From the digestive system constipation, diarrhea, nausea; very rarely – anorexia, dysphagia, gastroenteritis, stomatitis, caries.

Allergic reactions anaphylactic reactions, including shock.

From the blood and lymphatic system rarely – lymphadenopathy; very rarely – eosinophilia, splenomegaly.

From the metabolism very rarely – edema, weight loss, aversion to alcohol.

From the musculoskeletal system: rarely – arthralgia, arthritis.

From the nervous system rarely – emotional lability, confusion (stupor), seizures, anxiety, depression, dizziness, tremor, ataxia, headache.

From the respiratory system rarely – increased breathing (hyperventilation); in isolated cases – bronchospasm, nosebleed, hypoventilation, voice change.

From the reproductive system rarely – amenorrhea, impotence, menorrhagia, vaginal bleeding.

Other rarely – hematuria.

Contraindications

• Hypersensitivity to glatiramer acetate or mannitol.

The drug is not recommended for use in children and adolescents under 18 years of age, since adequate and strictly controlled clinical studies of the safety of the drug in this group of patients have not been conducted.

Use in Pregnancy and Lactation

Adequate and well-controlled studies of the safety of glatiramer acetate use during pregnancy have not been conducted. The use of Copaxone^®-Teva during pregnancy is possible only for absolute indications.

It is not known whether Glatiramer acetate is excreted in breast milk, so if it is necessary to use the drug during lactation, the expected benefit of therapy for the mother and the potential risk for the child should be weighed.

In experimental studies in animals, no mutagenic effect of glatiramer acetate and its negative effect on the parameters of the reproductive system, embryo development, and the birth process were revealed.

Use in Renal Impairment

Patients with impaired renal function should regularly monitor laboratory parameters.

Pediatric Use

The drug is not recommended for use in children and adolescents under 18 years of age, since adequate and strictly controlled clinical studies of the safety of the drug in this group of patients have not been conducted.

Special Precautions

The drug should be prescribed with caution to patients prone to allergic reactions and with cardiac pathology.

Patients with impaired renal function should regularly monitor laboratory parameters.

The patient should be informed about the technique of self-injections for the safe use of Copaxone^®-Teva and receive instructions on the use of antiseptic methods when preparing the injection solution and its administration. The first injection should be performed under the supervision of a qualified specialist. It is necessary to periodically monitor the patient’s understanding of the importance of using antiseptic treatment during self-injections. Patients should be informed about the inadmissibility of reusing needles and syringes, as well as the procedure for their safe disposal. Used needles and syringes should be placed in a rigid container and only then discarded. Patients should be informed about possible adverse reactions associated with the use of the drug.

Effect on the ability to drive vehicles and mechanisms

Based on available data, no special precautions are necessary for persons driving a car or complex machinery.

Overdose

There are no data on overdose of Copaxone^®-Teva.

Drug Interactions

The interaction between Copaxone^®-Teva and other drugs has not been sufficiently studied. During clinical trials, no significant drug interactions were identified, including the simultaneous use of Copaxone^®-Teva with drugs used for the therapy of multiple sclerosis, including corticosteroids (with simultaneous use for up to 28 days). Very rarely, the frequency of local reactions may increase.

Storage Conditions

The drug should be stored at a temperature from 2°C (35.6°F) to 8°C (46.4°F) (in a refrigerator). If refrigeration is not possible, the drug can be stored at a temperature from 15°C (59°F) to 25°C (77°F), but for no more than 1 month. If after this period the drug has not been used and is in the original packaging, it should be further stored in the refrigerator (2°-8°C (35.6°F-46.4°F)).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.