Glatiramer (Monograph)

Brand names: Copaxone, Glatopa [Web])
Drug class: Immunomodulatory Agents
- Immunomodulatory Agents
Chemical name: l-Glutamic acid polymer with l-alanine, l-lysine, and l-tyrosine, acetate
Molecular formula: C₅H₉NO₄ • C₃H_7-5H₉NO₄ • C₃H₇NO₂ • C₆H₁₄N₂O₂ • C₉H₁₁NO₃)_x • xC₂H₄O₂)
CAS number: 147245-92-9

Medically reviewed by Drugs.com on Aug 19, 2022. Written by ASHP.

Introduction

Synthetic polypeptide mixture containing 4 naturally occurring amino acids with immunomodulatory and disease-modifying activity in multiple sclerosis.

Uses for Glatiramer

Multiple Sclerosis (MS)

Treatment of adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary progressive MS.

Glatiramer acetate is one of several disease-modifying therapies used in the management of relapsing forms of MS. Although not curative, these therapies have all been shown to modify several measures of disease activity, including relapse rates, new or enhancing MRI lesions, and disability progression.

The American Academy of Neurology (AAN) recommends that disease-modifying therapy be offered to patients with relapsing forms of MS 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.

Has been evaluated for primary progressive MS (PPMS)^{† [off-label]}.

Glatiramer Dosage and Administration

General

Patient Monitoring

• Routine laboratory monitoring is not considered necessary in patients receiving glatiramer acetate.

Dispensing and Administration Precautions

• Administer the initial self-administered dose under the supervision of a qualified healthcare professional.

• Several preparations of glatiramer acetate are commercially available (e.g., Copaxone, Glatopa and other generic preparations), and there are 2 commercially available dosage strengths of the drug. Glatiramer acetate 20 mg/mL is administered once daily and glatiramer acetate 40 mg/mL is administered 3 times a week; the 2 different dosage strengths are not interchangeable.

Administration

Administer only by sub-Q injection; do not administer IV.

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.

Localized lipoatrophy and skin necrosis reported; to minimize risk, follow proper injection technique and rotate injection sites with each injection.

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

Immediate Post-injection Reaction

Acute injection reactions reported 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. Majority of symptoms occur within 1 hour, but may occur within seconds to minutes of administration.

Chest Pain

Transient chest pain reported, usually presenting >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 more than one 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 sites daily to minimize risk.

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.

Hepatic Injury

Hepatic injury, including liver failure and hepatitis with jaundice, reported. May occur at various times after treatment initiation, most often within 1–3 months; generally self-limited after discontinuation of the drug.

Specific Populations

Pregnancy

Insufficient information to determine whether there is a drug-associated risk when used during pregnancy. No fetal harm observed in animal reproduction studies.

Lactation

Not known whether glatiramer is distributed into milk; the effects on nursing infants or on milk production also unknown. Consider benefits of breast-feeding along with mother's clinical need for glatiramer acetate and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.

Has been used for pediatric-onset MS (POMS)^{† [off-label]}; however, well-controlled studies with prolonged follow-up needed to assess long-term efficacy and safety.

Geriatric Use

Not studied in geriatric patients.

Renal Impairment

Pharmacokinetics not studied.

Common Adverse Effects

The most common adverse effects reported with glatiramer acetate 20 mg/mL (≥10%) include injection site reactions, vasodilatation, rash, dyspnea, and chest pain.

The most common adverse effect reported with glatiramer acetate 40 mg/mL (≥10%) was injection site reactions.

Drug Interactions

Interactions with other drugs not fully evaluated to date.

No clinically important interactions reported with drugs commonly used in MS, 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 the prescription is refilled.

• Importance of clinicians instructing patients and/or caregivers on proper injection techniques (including use of aseptic technique and avoiding reuse of syringes and needles and proper disposal of such equipment).

• Risk of immediate 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. Clinicians should inform patients that these symptoms usually are transient, occur within seconds to minutes after injection, and self-limited, and do not require specific treatment.

• Importance of advising patients that they may experience chest pain either as part of an immediate 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 the injection site. Advise patients to follow proper injection technique and rotate injection areas and sites with each injection.

• Risk of hepatic injury. Importance of advising patients on signs and symptoms of hepatic injury (e.g., nausea, loss of appetite, dark colored urine, yellowing of skin or sclera). Advise patients to contact their healthcare provider immediately if they experience these symptoms.

• Importance of advising patients that the 20-mg/mL and 40-mg/mL strengths of glatiramer acetate are not interchangeable and are administered using different dosage schedules.

• Importance of informing patients of the recommended storage instructions for glatiramer acetate. 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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Reload page with references included

Frequently asked questions

• Where and how should Copaxone be injected?
• What happens if an MS patient stops taking Copaxone?
• How long can you take Copaxone?
• How long does it take for Copaxone to be effective?
• How does Copaxone work for multiple sclerosis?

View more FAQ

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