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Glatiramer Acetate


General


Pronunciation

(gla TIR a mer AS e tate)


Brand Names: U.S.

  • Copaxone
  • Glatopa

Indications


Use: Labeled Indications

Multiple sclerosis: Treatment of patients with relapsing forms of multiple sclerosis (MS)

Canadian labeling: Additional use (not in US labeling): Treatment of patients who have experienced a single demyelinating event, accompanied by abnormal MRI scans and are considered to be at risk of developing clinically definite MS, after alternative diagnoses are excluded.


Contraindications


Hypersensitivity to glatiramer acetate, mannitol, or any component of the formulation


Dosing and Administration


Dosing: Adult

Multiple sclerosis (MS) (relapsing): SubQ:

US labeling: Note: Glatiramer 20 mg/mL and 40 mg/mL formulations are not interchangeable.

MS (relapsing-remitting): 20 mg once daily or 40 mg 3 times per week administered at least 48 hours apart

Canadian labeling: MS (relapsing-remitting or at risk following single demyelinating event): 20 mg once daily


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied).


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer 's labeling.


Administration

For SubQ administration in the arms, abdomen, hips, or thighs; rotate injection sites to possibly minimize the occurrence of lipoatrophy. Do not administer IV. Administer the 40 mg dose on the same 3 days each week (eg, Monday, Wednesday, Friday) at least 48 hours apart. Allow syringe to stand at room temperature for 20 minutes prior to injection. Discard unused portions.


Storage

Store at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F). If needed, may store at 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F) for up to 1 month (refrigeration is preferred). Avoid exposure to high temperatures; protect from intense light. Do not freeze. Discard if syringe freezes.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Prefilled Syringe, Subcutaneous:

Copaxone: 20 mg/mL (1 mL) [contains mannitol]

Copaxone: 40 mg/mL (1 mL)

Glatopa: 20 mg/mL (1 mL) [contains mannitol]


Drug Interactions

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination


Adverse Reactions


>10%:

Cardiovascular: Vasodilatation (3% to 20%), chest pain (2% to 13%)

Central nervous system: Pain (20%), anxiety (13%)

Dermatologic: Skin rash (2% to 19%), diaphoresis (15%)

Gastrointestinal: Nausea (2% to 15%)

Hypersensitivity: Immediate hypersensitivity (2% to 16%; postinjection, including flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and/or urticaria)

Immunologic: Development of IgG antibodies (3 months: ≥3 x baseline: 80%; 12 months: 90%; ≥3 x baseline: 30%)

Infection: Infection (30%)

Local: Inflammation at injection site (2% to 49%), erythema at injection site (22% to 43%), pain at injection site (10% to 40%), itching at injection site (6% to 27%), residual mass at injection site (6% to 27%), swelling (1% to 19%)

Neuromuscular & skeletal: Weakness (22%), back pain (12%)

Respiratory: Dyspnea (3% to 14%), flu-like symptoms (3% to 14%), nasopharyngitis (11%)

1% to 10%:

Cardiovascular: Palpitations (7% to 9%), edema (8%), tachycardia (5%), facial edema (3%), peripheral edema (3%), syncope (3%), hypertension (1%)

Central nervous system: Migraine (4%), chills (2% to 3%), nervousness (2%), speech disturbance (2%), abnormal dreams (1%), emotional lability (1%), stupor (1%)

Dermatologic: Hyperhidrosis (7%), pruritus (5%), erythema (2% to 4%), urticaria (3%), skin atrophy ( ≥1%), warts ( ≥1%), eczema (1%), pustular rash (1%)

Endocrine & metabolic: Weight gain (3%), amenorrhea (1%), hypermenorrhea (1%)

Gastrointestinal: Vomiting (7%), gastroenteritis (6%), dysphagia (2%), aphthous stomatitis ( ≥1%), bowel urgency ( ≥1%), dental caries ( ≥1%), enlargement of salivary glands ( ≥1%), oral candidiasis ( ≥1%)

Genitourinary: Urinary urgency (5%), vulvovaginal candidiasis (4%), abnormal Pap smear ( ≥1%), hematuria ( ≥1%), vaginal hemorrhage ( ≥1%), impotence (1%)

Hematologic & oncologic: Bruise (8%), lymphadenopathy (7%), benign skin neoplasm (2%)

Hypersensitivity: Hypersensitivity (3%)

Infection: Abscess ( ≥1%), herpes zoster ( ≥1%)

Local: Bleeding at injection site (5%), hypersensitivity reaction at injection site (4%), fibrosis at injection site (2%), lipoatrophy at injection site ( ≤2%), abscess at injection site (1%)

Neuromuscular & skeletal: Neck pain (8%), tremor (4%), laryngospasm (2%)

Ophthalmic: Diplopia (3%), visual field defect (1%)

Respiratory: Rhinitis (7%), bronchitis (6%), cough (6%), laryngismus (5%), viral respiratory tract infection (3%), hyperventilation (1%)

Miscellaneous: Fever (3% to 6%)

<1% (Limited to important or life-threatening): Amyotrophy, anaphylactoid reaction, anemia, angina pectoris, angioedema, aphasia, arthritis, asthma, ataxia, atrial fibrillation, blepharoptosis, blindness, bradycardia, bursitis, carcinoma (breast, bladder, lung, ovarian), cardiac arrhythmia, cardiac failure, cardiomegaly, cardiomyopathy, cataract, cerebral edema, cerebrovascular accident, cholecystitis, cholelithiasis, CNS neoplasm, colitis, coma, corneal ulcer, coronary occlusion, Cushings syndrome, cyanosis, decreased libido, deep vein thrombophlebitis, depersonalization, dermatitis, dry eye syndrome, duodenal ulcer, eosinophilia, erythema nodosum, esophageal ulcer, esophagitis, facial paralysis, fibrocystic breast disease, fourth heart sound, fungal dermatitis, furunculosis, gastrointestinal carcinoma, gastrointestinal hemorrhage, gastrointestinal ulcer, genitourinary neoplasm, glaucoma, gout, hallucination, hematemesis, hepatic cirrhosis, hepatitis, hepatomegaly, hernia, hydrocephalus, hypercholesterolemia, hyperthyroidism, hypokinesia, hypotension, hypothyroidism, hypoventilation, increased appetite, leukemia, leukopenia, lupus erythematosus, lymphedema, maculopapular rash, malignant neoplasm of cervix, malignant neoplasm of skin, mania, memory impairment, meningitis, mitral valve prolapse syndrome, moon face, muscle spasm, mydriasis, myelitis, myocardial infarction, myoclonus, nephrolithiasis, nephrosis, neuralgia, optic neuritis, oral mucosa ulcer, orthostatic hypotension, osteomyelitis, otitis externa, ovarian cyst, pancreatitis, pancytopenia, paraplegia, pericardial effusion, peripheral vascular disease, photophobia, pneumonia, priapism, pseudolymphoma, psoriasis, psychotic depression, pulmonary embolism, pyelonephritis, rectal hemorrhage, renal failure, seizures, sepsis, serum sickness, skin hypertrophy, skin photosensitivity, skin pigmentation, splenomegaly, stomatitis, suicidal tendencies, systemic lupus erythematosus, systolic heart murmur, tenosynovitis, thrombocytopenia, thrombophlebitis, thrombosis, tissue necrosis at injection site, urethritis, vesicobullous rash, weight loss, xeroderma


Warnings/Precautions


Concerns related to adverse effects:

- Chest pain: May or may not occur with the immediate postinjection reaction; described as a transient pain usually resolving in a few minutes; often unassociated with other symptoms. Episodes usually begin ≥1 month after initiation of treatment.

- Hypersensitivity reactions: Anaphylactoid reactions (rare) have been reported.

- Immune response: Although there has not been a systematic evaluation of glatiramer 's potential to affect other immune functions, it may interfere with recognition of foreign antigens undermining the body 's tumor surveillance and defense system against infection.

- Lipoatrophy: May occur locally at injection site at various times after treatment (sometimes after several months) and may not resolve; to possibly minimize occurrence, advise patients to follow proper injection technique and rotate site with each injection. Skin necrosis has also been observed.

- Systemic reactions: Immediate postinjection systemic reactions occur in a substantial percentage of patients (~16% [20 mg/mL] and ~2% [40 mg/mL] in studies); symptoms (anxiety, chest pain, constriction of the throat, dyspnea, flushing, palpitations, urticaria) are usually self-limited and transient. These symptoms generally occur several months after initiation of treatment.

Concurrent drug therapy concerns:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

- Antigenic: Glatiramer acetate is antigenic and may possibly lead to the induction of untoward host responses. Glatiramer acetate-reactive antibodies (IgG subtype) form in most patients.


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Limited information is available related to the use of glatiramer acetate in pregnancy (Amato 2015; Fragoso 2014; Ghezzi 2013; Giannini 2012). Until additional information is available, consideration should be given to discontinuing treatment if a woman becomes pregnant, or 1 month prior to becoming pregnant in women with mild disease (Coyle, 2012; Ghezzi 2013; Houtchens, 2013; Lu, 2013).


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Pharmacology

Glatiramer is a mixture of random polymers of four amino acids; L-alanine, L-glutamic acid, L-lysine, and L-tyrosine, the resulting mixture is antigenically similar to myelin basic protein, which is an important component of the myelin sheath of nerves; glatiramer is thought to induce and activate T-lymphocyte suppressor cells specific for a myelin antigen, it is also proposed that glatiramer interferes with the antigen-presenting function of certain immune cells opposing pathogenic T-cell function


Distribution

A small percentage of intact and partial hydrolyzed drug is presumed to enter lymphatic circulation.


Metabolism

SubQ: Large percentage hydrolyzed locally


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience flushing, nausea, vomiting, loss of strength and energy, or back pain. Have patient report immediately to prescriber signs of infection, angina, tachycardia, passing out, arrhythmia, vision changes, anxiety, sweating a lot, dizziness, shortness of breath, enlarged lymph nodes, tremors, or severe injection site irritation or edema (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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