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.^{1 2 3 4 5 6 7 23}

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.^{1 23 28 29 35}

Glatiramer acetate is one of several disease-modifying therapies used in the management of relapsing forms of MS.^{76 77} 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.^{76 78}

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.⁷⁶ 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.^{76 77}

Has been evaluated for primary progressive MS (PPMS)^{† [off-label]}.^{31 76}

Glatiramer Dosage and Administration

General

Patient Monitoring

• Routine laboratory monitoring is not considered necessary in patients receiving glatiramer acetate.⁷

Dispensing and Administration Precautions

• Administer the initial self-administered dose under the supervision of a qualified healthcare professional.¹

• 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.^{1 28 29 76} 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.¹

Administration

Administer only by sub-Q injection; do not administer IV.¹

Sub-Q Administration

Commercially available prefilled syringes intended for single use only; discard unused portion.¹

Allow prefilled syringes to reach room temperature by removing from refrigerator about 20 minutes prior to use.¹

Inject sub-Q into the arm, abdomen, hip, or thigh.^{1 6}

Localized lipoatrophy and skin necrosis reported; to minimize risk, follow proper injection technique and rotate injection sites with each injection.^{1 22}

Dosage

Available as glatiramer acetate; dosage expressed in terms of the salt.¹

Adults

Multiple Sclerosis

Sub-Q

Dosage recommendations differ based on dosage strength (20 or 40 mg/mL) used.¹ Dosage strengths are not interchangeable.¹

If using the 20-mg/mL injection, recommended dosage is 20 mg once daily.¹

If using the 40-mg/mL injection, recommended dosage is 40 mg 3 times a week (administer injections at least 48 hours apart).¹

Special Populations

No special population dosage recommendations at this time.¹

Cautions for Glatiramer

Contraindications

• Known hypersensitivity to glatiramer acetate or mannitol.¹

Warnings/Precautions

Immediate Post-injection Reaction

Acute injection reactions reported after sub-Q injection.¹ Symptoms, which are generally transient and self-limited and do not require treatment,¹ include flushing,^{1 2 6 7} chest pain^{1 2 6} or tightness,^{6 7} palpitations,^{1 2 5 6 7} anxiety,^{1 2 5 6 7} dyspnea,^{1 2 5 6 7} constriction of the throat,¹ tachycardia,¹ and urticaria.^{1 23} Majority of symptoms occur within 1 hour, but may occur within seconds to minutes of administration.¹

Chest Pain

Transient chest pain reported, usually presenting >1 month after initiation of therapy.¹ Some episodes occurred as part of immediate post-injection reactions, but many did not.¹ Episodes generally last only a few minutes, often are not associated with other symptoms, and do not appear to produce clinically important sequelae.¹ Some patients experience more than one such episode.¹

Lipoatrophy and Skin Necrosis

Localized lipoatrophy (i.e., loss of subcutaneous fat) and, rarely, skin necrosis at the injection site reported.^{1 21 22 23} Lipoatrophy may occur at various times after treatment initiation, sometimes after several months and is thought to be permanent.^{1 22} No known treatment for lipoatrophy.^{1 22}

Advise patients to follow proper injection technique and rotate injection sites daily to minimize risk.¹

Potential Effects on Immune Response

Possible modification of immune response and interference with useful immune function.¹

Possible interference with the recognition of foreign antigens, which may undermine the body’s tumor surveillance ability and defenses against infection.¹

Possibility of adverse effects resulting from continued alteration of cellular immunity associated with chronic administration of the drug.¹

Antibody Formation

Development of IgG antibodies to glatiramer reported in most patients;^{1 10} however, data to date indicate that antibodies do not neutralize therapeutic effects.^{3 18 20}

Animal studies suggest that immune complexes are deposited in renal glomeruli.¹

Hepatic Injury

Hepatic injury, including liver failure and hepatitis with jaundice, reported.^{1 32} May occur at various times after treatment initiation, most often within 1–3 months; generally self-limited after discontinuation of the drug.³²

Specific Populations

Pregnancy

Insufficient information to determine whether there is a drug-associated risk when used during pregnancy.¹ No fetal harm observed in animal reproduction studies.¹

Lactation

Not known whether glatiramer is distributed into milk; the effects on nursing infants or on milk production also unknown.¹ 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.¹

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.¹

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.^{33 34}

Geriatric Use

Not studied in geriatric patients.¹

Renal Impairment

Pharmacokinetics not studied.¹

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.^{1 2 5 23}

The most common adverse effect reported with glatiramer acetate 40 mg/mL (≥10%) was injection site reactions.^{1 30}

Drug Interactions

Interactions with other drugs not fully evaluated to date.¹

No clinically important interactions reported with drugs commonly used in MS, including concurrent corticosteroid therapy for up to 28 days.¹ Not formally evaluated in combination with interferon beta.^{1 6}

Glatiramer Pharmacokinetics

Distribution

Following sub-Q injection, some portion of the dose may enter the lymphatic circulation and some may enter systemic circulation.¹ Does not appear to cross the blood-brain barrier.⁶

Elimination

Metabolism

Substantial portion of sub-Q dose appears to be hydrolyzed locally at injection site to small oligopeptides and free amino acids.^{1 6}

Stability

Storage

Parenteral

Injection

2–8°C; protect from light.¹ May be stored at room temperature (15–30°C) for ≤1 month.¹ Do not freeze.¹

Actions

• Mechanism of action not fully elucidated;¹ appears to modify immune processes responsible for the pathogenesis of MS.^{1 6 15}

• 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.^{1 6 15}

Advice to Patients

• Importance of reading the manufacturer’s patient information prior to beginning glatiramer acetate therapy and each time the prescription is refilled.¹

• 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).¹

• Risk of immediate post-injection reaction.¹ Importance of advising patients that glatiramer acetate may cause various symptoms after injection, including flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and urticaria.¹ 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.¹

• Importance of advising patients that they may experience chest pain either as part of an immediate post-injection reaction or in isolation.¹ Patients should be informed that the pain should be transient (usually lasting only for a few minutes).¹ Some patients may experience more than one such episode, usually beginning at least one month after beginning treatment.¹ Advise patients to seek medical attention if they experience chest pain of unusual duration or intensity.¹

• Risk of lipoatrophy and skin necrosis at the injection site.^{1 21 22 23} Advise patients to follow proper injection technique and rotate injection areas and sites with each injection.¹

• Risk of hepatic injury.¹ 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).¹ Advise patients to contact their healthcare provider immediately if they experience these symptoms.¹

• 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.¹

• Importance of informing patients of the recommended storage instructions for glatiramer acetate.¹ Importance of advising patients not to expose the drug to higher temperatures, freezing temperatures, or to intense light.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of patient informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of informing patients of other important precautionary information.¹ (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

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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