Class: Immunomodulatory Agents
Immunomodulatory Agents
Chemical Name: l-Glutamic acid polymer with l-alanine, l-lysine, and l-tyrosine, acetate
Molecular Formula: C5H9NO4 • C3H7-5H9NO4 • C3H7NO2 • C6H14N2O2 • C9H11NO3)x • xC2H4O2)
CAS Number: 147245-92-9
Brands: Copaxone, Glatopa
Uses for Glatiramer
Multiple Sclerosis (MS)
Treatment of patients with relapsing forms of MS (e.g., relapsing-remitting MS [RRMS]).
Glatiramer acetate is one of several disease-modifying therapies used in the management of RRMS. Although not curative, these therapies have all been shown to modify several measures of disease activity, including relapse rates, new or enhancing magnetic resonance imaging (MRI) lesions, and disability progression.
The American Academy of Neurology (AAN) recommends that disease-modifying therapy be offered to patients with RRMS who have had recent relapses and/or MRI activity. Clinicians should consider adverse effects, tolerability, method of administration, safety, efficacy, and cost of the drugs in addition to patient preferences when selecting an appropriate therapy.
Clinical experience suggests that efficacy of glatiramer acetate is generally similar to that of interferon beta. Efficacy of glatiramer acetate compared with other disease-modifying therapies (e.g., fingolimod, mitoxantrone, natalizumab) not fully evaluated to date.
Glatiramer Dosage and Administration
Administration
Administer only by sub-Q injection; do not administer IV.
Administer initial self-administered dose under supervision of a qualified clinician.
Several preparations of glatiramer acetate are commercially available (e.g., Copaxone, Glatopa and other generic preparations), and there are 2 available dosage strengths. The 20-mg/mL injection is administered once daily and the 40-mg/mL injection is administered 3 times a week; the 2 dosage strengths are not interchangeable.
Sub-Q Administration
Commercially available prefilled syringes intended for single use only; discard unused portion.
Allow prefilled syringes to reach room temperature by removing from refrigerator about 20 minutes prior to use.
Inject sub-Q into the arm, abdomen, hip, or thigh.
To minimize risk of localized lipoatrophy and skin necrosis, follow proper injection technique and rotate injection areas and sites with each injection. (See Lipoatrophy and Skin Necrosis under Cautions.)
Dosage
Available as glatiramer acetate; dosage expressed in terms of the salt.
Adults
Multiple Sclerosis
Sub-Q
Dosage recommendations differ based on dosage strength (20 or 40 mg/mL) used. Dosage strengths are not interchangeable.
If using the 20-mg/mL injection, recommended dosage is 20 mg once daily.
If using the 40-mg/mL injection, recommended dosage is 40 mg 3 times a week (administer injections at least 48 hours apart).
Special Populations
No special population dosage recommendations at this time.
Cautions for Glatiramer
Contraindications
- Known hypersensitivity to glatiramer acetate or mannitol.
Warnings/Precautions
Sensitivity Reactions
Hypersensitivity Reactions
Injection site hypersensitivity, allergic reactions, and anaphylactic or anaphylactoid reactions reported, including rare cases of anaphylaxis accompanied by anti-glatiramer IgE antibodies. Some reactions developed from one to several months or more after initiating therapy.
General Precautions
Post-injection Reaction
Acute injection reactions reported in some patients immediately after sub-Q injection. Symptoms, which are generally transient and self-limited and do not require treatment, include flushing, chest pain or tightness, palpitations, anxiety, dyspnea, constriction of the throat, tachycardia, and urticaria.
Reactions generally occur several months after initiation of therapy (although may occur earlier); individual patients may experience one or several episodes of these symptoms. During the postmarketing period, some patients with similar symptoms reportedly received emergency medical care.
Not currently known whether reactions have an immunologic or nonimmunologic mechanism or whether multiple episodes in a given patient have similar mechanisms.
Chest Pain
Transient chest pain reported, generally >1 month after initiation of therapy. Some episodes occurred as part of immediate post-injection reactions, but many did not. Episodes generally last only a few minutes, often are not associated with other symptoms, and do not appear to produce clinically important sequelae. Some patients experience >1 such episode.
Lipoatrophy and Skin Necrosis
Localized lipoatrophy (i.e., loss of subcutaneous fat) and, rarely, skin necrosis at the injection site reported. Lipoatrophy may occur at various times after treatment initiation, sometimes after several months and is thought to be permanent. No known treatment for lipoatrophy.
Advise patients to follow proper injection technique and rotate injection areas and sites daily to minimize risk of these events.
Potential Effects on Immune Response
Possible modification of immune response and interference with useful immune function.
Possible interference with the recognition of foreign antigens, which may undermine the body’s tumor surveillance ability and defenses against infection.
Possibility of adverse effects resulting from continued alteration of cellular immunity associated with chronic administration of the drug.
Antibody Formation
Development of IgG antibodies to glatiramer reported in most patients; however, data to date indicate that antibodies do not neutralize therapeutic effects.
Animal studies suggest that immune complexes are deposited in renal glomeruli.
Specific Populations
Pregnancy
Category B.
Lactation
Not known whether glatiramer is distributed into milk. Use with caution in nursing women.
Pediatric Use
Safety and efficacy not established in pediatric patients <18 years of age.
Geriatric Use
Not studied in geriatric patients.
Common Adverse Effects
20-mg/mL injection: Injection site reactions (e.g., pain, erythema, inflammation, pruritus, mass, edema, hypersensitivity, fibrosis, atrophy or lipoatrophy, necrosis), vasodilatation, rash, dyspnea, chest pain.
40-mg/mL injection: Injection site reactions.
Interactions for Glatiramer
Interactions with other drugs not fully evaluated to date.
No clinically important interactions reported in clinical trials between glatiramer and drugs commonly used in multiple sclerosis, including concurrent corticosteroid therapy for up to 28 days. Not formally evaluated in combination with interferon beta.
Glatiramer Pharmacokinetics
Distribution
Following sub-Q injection, some portion of the dose may enter the lymphatic circulation and some may enter systemic circulation. Does not appear to cross the blood-brain barrier.
Elimination
Metabolism
Substantial portion of sub-Q dose appears to be hydrolyzed locally at injection site to small oligopeptides and free amino acids.
Stability
Storage
Parenteral
Injection
2–8°C; protect from light. May be stored at room temperature (15–30°C) for ≤1 month. Do not freeze.
Actions
- Mechanism of action not fully elucidated; appears to modify immune processes responsible for the pathogenesis of MS.
- Induces and activates drug-specific suppressor T-cells that migrate into the CNS and down-regulate immune response (e.g., inflammation) to myelin antigens in the periphery.
Advice to Patients
- Importance of reading the manufacturer’s patient information prior to beginning glatiramer acetate therapy and each time prescription is refilled.
- Importance of clinicians instructing patients and/or caregivers in proper injection techniques (including use of aseptic technique) and about avoiding reuse of syringes and needles and proper disposal of such equipment.
- Risk of post-injection reaction. Importance of advising patients that glatiramer acetate may cause various symptoms after injection, including flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and urticaria. Importance of informing patients that these symptoms usually are transient and self-limited and do not require specific treatment. However, patients should be advised to contact their clinician immediately if any serious reactions (e.g., flushing, chest pain, tachycardia, anxiety, breathing difficulties or tightness in the throat, swelling, rash, hives, itching) occur immediately after injection. Patients also should be informed that such reactions may occur early or begin several months after initiation of treatment, and that they may experience one or several episodes of these symptoms.
- Importance of advising patients that they may experience chest pain either as part of a post-injection reaction or in isolation. Patients should be informed that the pain should be transient (usually lasting only for a few minutes). Some patients may experience more than one such episode, usually beginning at least one month after beginning treatment. Advise patients to seek medical attention if they experience chest pain of unusual duration or intensity.
- Risk of lipoatrophy and skin necrosis at injection site. Advise patients to follow proper injection technique and rotate injection areas and sites with each injection.
- Importance of informing patients of the recommended storage instructions for glatiramer acetate (see Storage under Stability). Importance of advising patients not to expose the drug to higher temperatures, freezing temperatures, or to intense light.
- Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
- Importance of patient informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
- Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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Glatiramer Acetate |
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Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
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Parenteral |
Injection, for subcutaneous use |
20 mg/1 mL* |
Copaxone (available as 1-mL prefilled syringe) |
Teva Neuroscience |
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Glatiramer Acetate Injection |
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Glatopa (available as 1-mL prefilled syringe) |
Sandoz |
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40 mg/1 mL* |
Copaxone (available as 1-mL prefilled syringe) |
Teva Neuroscience |
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Glatopa (available as 1-mL prefilled syringe) |
Sandoz |
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