Glatiramer
FDA Drug Information • Also known as: Glatiramer Acetate
- Brand Names
- Glatiramer Acetate
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
⚠ Boxed Warning (Black Box)
WARNING: ANAPHYLACTIC REACTIONS Cases of life-threatening and fatal anaphylaxis have been reported with glatiramer acetate injection. Anaphylaxis can occur at any time following initiation of therapy, from as early as after the first dose, up to years following initiation of therapy.
Make patients aware of the symptoms of anaphylaxis, which may overlap with those of an immediate post-injection reaction; instruct them to seek immediate medical care should these symptoms occur. Prompt identification of anaphylaxis is important to avoid a delay in treatment [see Warnings and Precautions (5.1) ] . Glatiramer acetate injection is contraindicated in patients with a history of hypersensitivity reactions to glatiramer acetate injection, including anaphylaxis. If an anaphylactic reaction occurs, treatment with glatiramer acetate injection must be immediately discontinued. Unless a clear alternative etiology is identified, glatiramer acetate injection must be permanently discontinued [see Contraindications (4) and Warnings and Precautions (5.1) ] . WARNING: ANAPHYLACTIC REACTIONS See full prescribing information for complete boxed warning. Life-threatening and fatal anaphylaxis, which can occur at any time following initiation of therapy (from as early as after the first dose, up to years after initiation of treatment), has been reported in patients receiving glatiramer acetate injection. Make patients aware of the symptoms of anaphylaxis, which may overlap with those of an immediate post-injection reaction. Prompt identification of anaphylaxis is important to avoid a delay in treatment ( 5.1 ). Glatiramer acetate injection is contraindicated in patients with a history of hypersensitivity reactions to glatiramer acetate injection, including anaphylaxis ( 4 ).Description
11 DESCRIPTION Glatiramer acetate, the active ingredient of glatiramer acetate injection, consists of the acetate salts of synthetic polypeptides, containing four naturally occurring amino acids: L-glutamic acid, L-alanine, L-tyrosine, and L-lysine with an average molar fraction of 0.141, 0.427, 0.095, and 0.338, respectively. The average molecular weight of glatiramer acetate is 5,000 – 9,000 daltons. Glatiramer acetate is identified by specific antibodies. Chemically, glatiramer acetate is designated L-glutamic acid polymer with L-alanine, L-lysine and L-tyrosine, acetate (salt). Its structural formula is: Glatiramer acetate is a clear, colorless to slightly yellow, sterile, nonpyrogenic solution for subcutaneous injection. Each 1 mL of glatiramer acetate solution contains 40 mg of glatiramer acetate and the following inactive ingredient: 40 mg of mannitol. The pH of the solutions is approximately 5.5 to 7.0. The biological activity of glatiramer acetate is determined by its ability to block the induction of experimental autoimmune encephalomyelitis (EAE) in mice. Glatiramer Acetate Structural Formula
What Is Glatiramer Used For?
1 INDICATIONS AND USAGE Glatiramer acetate injection is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Glatiramer acetate injection is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults ( 1 ).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION
For subcutaneous injection only; doses are not interchangeable ( 2.1 ) Glatiramer acetate injection 40 mg/mL three times per week ( 2.1 ) Before use, allow the solution to warm to room temperature ( 2.2 ) 2.1 Recommended Dose Glatiramer acetate injection is for subcutaneous use only [see Dosage and Administration (2.2) ] . Do not administer intravenously. The dosing schedule depends on the product strength that is selected. The recommended dose is: Glatiramer acetate injection 40 mg per mL: administer three times per week and at least 48 hours apart Glatiramer acetate injection 20 mg per mL and glatiramer acetate injection 40 mg per mL are not interchangeable. 2.2 Instructions for Use Remove one blister-packaged prefilled syringe from the refrigerated carton. Let the prefilled syringe stand at room temperature for 20 minutes to allow the solution to warm to room temperature. Visually inspect the syringe for particulate matter and discoloration prior to administration. The solution in the syringe should appear clear, colorless to slightly yellow. If particulate matter or discoloration is observed, discard the syringe. Areas for subcutaneous self-injection include arms, abdomen, hips, and thighs. The prefilled syringe is for single use only. Discard unused portions. Using an autoinjector that is not compatible for use with Mylan’s glatiramer acetate injection may increase the risk for medication errors, such as dose omission or administration of a partial dose [see Warnings and Precautions (5.7) ] .Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling:
Anaphylactic Reactions [see Warnings and Precautions (5.1) ] Immediate Post-Injection Reaction [see Warnings and Precautions (5.2) ] Chest Pain [see Warnings and Precautions (5.3) ] Lipoatrophy and Skin Necrosis [see Warnings and Precautions (5.4) ] Potential Effects on Immune Response [see Warnings and Precautions (5.5) ] Hepatic Injury [see Warnings and Precautions (5.6) ] In controlled studies of glatiramer acetate injection 20 mg/mL, most common adverse reactions (≥ 10% and ≥ 1.5 times higher than placebo) were: injection site reactions, vasodilatation, rash, dyspnea, and chest pain ( 6.1 ) In a controlled study of glatiramer acetate injection 40 mg/mL, most common adverse reactions (≥ 10% and ≥ 1.5 times higher than placebo) were: injection site reactions ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Incidence in Controlled Clinical Trials Glatiramer Acetate Injection 20 mg per mL per day Among 563 patients treated with glatiramer acetate injection in blinded placebo-controlled trials, approximately 5% of the subjects discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: injection site reactions, dyspnea, urticaria, vasodilatation, and hypersensitivity. The most common adverse reactions were: injection site reactions, vasodilatation, rash, dyspnea, and chest pain. Table 1 lists signs and symptoms that occurred in at least 2% of patients treated with glatiramer acetate injection 20 mg per mL in the placebo-controlled trials. These signs and symptoms were numerically more common in patients treated with glatiramer acetate injection than in patients treated with placebo. Adverse reactions were usually mild in intensity . Table 1: Adverse Reactions in Controlled Clinical Trials with an Incidence ≥ 2% of Patients and More Frequent with Glatiramer Acetate Injection (20 mg per mL Daily) than with Placebo Glatiramer Acetate Injection 20 mg/mL (n = 563) % Placebo (n = 564) % Blood and Lymphatic System Disorders Lymphadenopathy 7 3 Cardiac Disorders Palpitations 9 4 Tachycardia 5 2 Eye Disorders Eye Disorder 3 1 Diplopia 3 2 Gastrointestinal Disorders Nausea 15 11 Vomiting 7 4 Dysphagia 2 1 General Disorders and Administration Site Conditions Injection Site Erythema 43 10 Injection Site Pain 40 20 Injection Site Pruritus 27 4 Injection Site Mass 26 6 Asthenia 22 21 Pain 20 17 Injection Site Edema 19 4 Chest Pain 13 6 Injection Site Inflammation 9 1 Edema 8 2 Injection Site Reaction 8 1 Pyrexia 6 5 Injection Site Hypersensitivity 4 0 Local Reaction 3 1 Chills 3 1 Face Edema 3 1 Edema Peripheral 3 2 Injection Site Fibrosis 2 1 Injection Site Atrophy Injection site atrophy comprises terms relating to localized lipoatrophy at injection site 2 0 Immune System Disorders Hypersensitivity 3 2 Infections and Infestations Infection 30 28 Influenza 14 13 Rhinitis 7 5 Bronchitis 6 5 Gastroenteritis 6 4 Vaginal Candidiasis 4 2 Metabolism and Nutrition Disorders Weight Increased 3 1 Musculoskeletal and Connective Tissue Disorders Back Pain 12 10 Neoplasms Benign, Malignant and Unspecified (Incl Cysts and Polyps) Benign Neoplasm of Skin 2 1 Nervous System Disorders Tremor 4 2 Migraine 4 2 Syncope 3 2 Speech Disorder 2 1 Psychiatric Disorders Anxiety 13 10 Nervousness 2 1 Renal and Urinary Disorders Micturition Urgency 5 4 Respiratory, Thoracic and Mediastinal Disorders Dyspnea 14 4 Cough 6 5 Laryngospasm 2 1 Skin and Subcutaneous Tissue Disorders Rash 19 11...Contraindications
4 CONTRAINDICATIONS Glatiramer acetate injection is contraindicated in patients with known hypersensitivity to glatiramer acetate or mannitol. Reactions have included anaphylaxis [see Warnings and Precautions (5.1) ] . Known hypersensitivity to glatiramer acetate or mannitol ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Available data from pharmacovigilance and published observational studies over decades of use with glatiramer acetate during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes ( see Data ). Administration of glatiramer acetate by subcutaneous injection to pregnant rats and rabbits resulted in no adverse effects on embryofetal or offspring development (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Data from pharmacovigilance and published observational studies have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes when glatiramer acetate was used during pregnancy. However, the published comparative observational studies have methodological limitations, such as short exposure duration during pregnancy, confounding, selection bias, and exposure misclassification. Animal Data In rats or rabbits receiving glatiramer acetate by subcutaneous injection during the period of organogenesis, no adverse effects on embryofetal development were observed at doses up to 37.5 mg/kg/day (18 and 36 times, respectively, the therapeutic human dose of 20 mg/day on a mg/m 2 basis). In rats receiving subcutaneous glatiramer acetate at doses of up to 36 mg/kg from day 15 of pregnancy throughout lactation, no significant effects on delivery or on offspring growth and development were observed.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Glatiramer Acetate Injection is a clear, colorless to slightly yellow, sterile, nonpyrogenic solution in a 1 mL single-dose, prefilled syringe with fixed ½ inch 29 gauge needle supplied as:
40 mg/mL in a single-dose, prefilled syringe with a light blue plunger, in individual blister packages supplied in 12-count cartons (NDC 0378-6961-12). Some glatiramer acetate products can be administered by an optional compatible autoinjector. Compatible autoinjectors are supplied separately if available, but the availability of compatible autoinjectors may change with time [see Warnings and Precautions (5.7) and Patient Counseling Information (17) ] . Store glatiramer acetate injection refrigerated at 2° to 8°C (36° to 46°F). If needed, the patient may store glatiramer acetate injection at room temperature, 15° to 30°C (59° to 86°F), for up to one month, but refrigeration is preferred. Avoid exposure to higher temperatures or intense light. Do not freeze glatiramer acetate injection. If a glatiramer acetate syringe freezes, it should be discarded. PHARMACIST: Dispense a Medication Guide with each prescription.About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.