Copaxone

— THERAPEUTIC CATEGORIES —
  • Multiple sclerosis
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Copaxone Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Glatiramer acetate 20mg/mL, 40mg/mL; soln for SC inj; contains mannitol; preservative-free.

    Pharmacological Class

    Immunomodulator.

    How Supplied

    Single-dose prefilled syringes 20mg/mL—30; 40mg/mL—12

    How Supplied

    Copaxone (glatiramer acetate injection) is a clear, colorless to slightly yellow, sterile, nonpyrogenic solution supplied as: 

    • 20 mg per mL in a single-dose, prefilled syringe with a white plunger, in individual blister packages supplied in 30-count cartons. 

    • 40 mg per mL in a single-dose, prefilled syringe with a blue plunger, in individual blister packages supplied in 12-count cartons.

    An optional autoinjector is available by prescription separately. Ensure Teva’s Copaxone is used with a compatible autoinjector if an optional autoinjector is prescribed.

    Storage

    Store Copaxone refrigerated at 2°C to 8°C (36°F to 46°F). If needed, the patient may store Copaxone at room temperature, 15°C to 30°C (59°F to 86°F), for up to one month, but refrigeration is preferred. Avoid exposure to higher temperatures or intense light. Do not freeze Copaxone. If a Copaxone syringe freezes, it should be discarded.

    Manufacturer

    Teva Neuroscience

    Generic Availability

    YES

    Mechanism of Action

    The mechanism(s) by which glatiramer acetate exerts its effects in patients with multiple sclerosis (MS) are not fully understood. However, glatiramer acetate is thought to act by modifying immune processes that are believed to be responsible for the pathogenesis of MS.

    Copaxone Indications

    Indications

    Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

    Copaxone Dosage and Administration

    Adult

    Supervise 1st dose. Use a compatible autoinjector. Give only by SC inj into arms, abdomen, hips, thighs. Rotate inj sites. ≥18yrs: 20mg once daily or 40mg three times weekly (at least 48hrs apart). The 20mg/mL and 40mg/mL injections are not interchangeable.

    Children

    <18yrs: not established.

    Copaxone Contraindications

    Not Applicable

    Copaxone Boxed Warnings

    Not Applicable

    Copaxone Warnings/Precautions

    Warnings/Precautions

    Risk of immediate post-injection reactions. May potentially interfere with immune functions. Consider discontinuation if liver dysfunction occurs. Renal impairment. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Immediate Post-Injection Reaction

    • A constellation of symptoms may occur immediately (within seconds to minutes, with the majority of symptoms observed within 1 hour) after injection and included at least 2 of the following: flushing, chest pain, palpitations, tachycardia, anxiety, dyspnea, constriction of the throat, and urticaria.

    • In general, symptoms have their onset several months after initiation, but may occur earlier. Symptoms were typically transient and self-limited and did not require treatment.

    Chest Pain

    • The temporal relationship of chest pain to an injection was not always known in clinical studies. The pain was transient and episodes usually began at least 1 month after initiation.

    Lipoatrophy and Skin Necrosis

    • Skin necrosis was observed only in the postmarketing setting.

    • Lipoatrophy may occur and is thought to be permanent. 

    • To minimize these events, advise to follow proper injection technique and to rotate injection sites.

    Potential Effects on Immune Response 

    • May interfere with immune functions. May lead to the induction of host responses that are untoward, but systematic surveillance for these effects has not been undertaken.

    Hepatic Injury

    • Cases of hepatic injury, some severe, including liver failure and hepatitis with jaundice. This has occurred from days to years after initiation.

    • Consider discontinuing if signs or symptoms of liver dysfunction occur.

    Glatiramer Acetate Products and Administration Errors

    • Medication errors have occurred when glatiramer acetate products are administered with incompatible autoinjectors.
    • Some glatiramer acetate products may be given with an optional compatible autoinjector, but not all products are compatible.
    • Using an optional autoinjecto that is not compatible may increase the risk for medication errors.

    Pregnancy Considerations

    Risk Summary

    • Available human data in pregnant women are not sufficient to support conclusions about drug-associated risk for major birth defects and miscarriage. 

    • There are no adequate and well-controlled studies of Copaxone in pregnant women.

    Nursing Mother Considerations

    Risk Summary

    • Consider the developmental and health benefits of breastfeeding with the mother’s clinical need for Copaxone and any potential adverse effects on the breastfed infant from Copaxone or from the underlying maternal condition. 

    Pediatric Considerations

    Safety and effectiveness have not been established in patients under 18 years of age.

    Geriatric Considerations

    Not studied.

    Renal Impairment Considerations

    The pharmacokinetics of glatiramer acetate in patients with impaired renal function have not been determined. 

    Copaxone Pharmacokinetics

    See Literature

    Copaxone Interactions

    Not Applicable

    Copaxone Adverse Reactions

    Adverse Reactions

    Inj site reactions, vasodilatation, rash, dyspnea, chest pain, asthenia, infection, pain, nausea, anxiety; rare: lipoatrophy, skin necrosis.

    Copaxone Clinical Trials

    Clinical Trials

    Evidence supporting the effectiveness of Copaxone derives from 5 placebo-controlled trials, four of which used a Copaxone dose of 20 mg per mL per day and one of which used a Copaxone dose of 40 mg per mL 3 times per week.

     

    Study 1 - Copaxone 20 mg per mL per day  

    • The single-center study enrolled 50 patients who were diagnosed with RRMS and had at least 2 exacerbations during the 2 years prior to starting the study. Patients were randomly assigned 1:1 to receive Copaxone 20 mg per mL subcutaneously daily or placebo. 

    • The protocol-specified primary outcome measure was the proportion of patients in each treatment group who remained exacerbation free for the 2 years of the trial, but two other important outcomes were also specified as endpoints: the frequency of attacks during the trial, and the change in the number of attacks compared with the number which occurred during the previous 2 years.

    • Results showed that patients treated with Copaxone achieved the following clinical outcomes at 2 years compared with placebo, respectively:

      • % relapse-free patients: 56% (n=14/25) vs 28% (n=7/25) (P =.085)

      • Mean relapse frequency: 0.6/2 years vs 2.4/2 years (P =.005)

      • Reduction in relapse rate compared to prestudy: 3.2 vs 1.6 (P =.025)

      • Median time to first relapse (days): >700 vs 150 (P =.03)

      • % of progression-free patients: 80% (n=20/25) vs 52% (n=13/25) (P =.07)

    Study 2 - Copaxone 20 mg per mL per day  

    • The multicenter trial had a similar design as Study 1 and enrolled 251 patients (Copaxone [n=125]; placebo [n=126]). The primary outcome measure was the Mean 2-Year Relapse Rate.

    • Results showed that patients treated with Copaxone achieved the following clinical outcomes at 2 years compared with placebo, respectively:

      • Mean number of relapses: 1.19 per 2 years vs 1.68 per 2 years (P =.055)

      • % relapse-free patients: 34% (n=42/125) vs 27% (n=34/126) (P =.25)

      • Median time to first relapse (days): 287 vs 198 (P =.23)

      • % of progression-free patients: 78% (n=98/125) vs 75% (n=95/126) (P =.48)

      • Mean change in DSS: -0.05 vs +0.21 (P =.023)

    Study 3 - Copaxone 20 mg per mL per day 

    • 481 patients who had recently (within 90 days) experienced an isolated demyelinating event and who had lesions typical of multiple sclerosis on brain MRI were randomized to receive either Copaxone 20 mg per mL (n=243) or placebo (n=238). The primary outcome measure was time to development of a second exacerbation. 

    • Results showed that patients treated with Copaxone achieved a significant delay in the time to development of a second exacerbation compared to placebo (Hazard Ratio =0.55; 95% CI, 0.40-0.77). The Kaplan-Meier estimates of the percentage of patients developing a relapse within 36 months were 42.9% in the placebo group and 24.7% in the Copaxone group.

    • There were fewer new T2 lesions at the last observation for patients treated with Copaxone (rate ratio 0.41; confidence interval 0.28-0.59; P <.0001). Moreover, patients treated with Copaxone achieved lower baseline-adjusted T2 lesion volume at the last observation (ratio of 0.89; confidence interval 0.84-0.94; P =.0001).

    Study 4 - Copaxone 20 mg per mL per day 

    • 239 patients with RRMS were randomly assigned 1:1 to receive either Copaxone 20 mg/mL or placebo for 9 months. The study used MRI parameters as both primary and secondary endpoints, and patients underwent monthly MRI scanning. The primary endpoint for the double-blind phase was the total cumulative number of T1 Gd-enhancing lesions over the 9 months.

    • Results showed that patients treated with Copaxone had a lower median of cumulative number of T1 Gd-enhancing lesions compared with those treated with placebo (11 vs 17, respectively; P =.003).

    Study 5 - Copaxone 40 mg per mL 3 times per week

    • The double-blind, placebo-controlled, multinational study included a total of 1404 patients with RRMS who had a median of 2 relapses in the 2 years prior to screening and had not received any interferon-beta for at least 2 months prior to screening. Patients were randomly assigned 2:1 to receive either Copaxone 40 mg per mL (n=943) or placebo (n=461) three times a week for 12 months.

    • The primary outcome measure was the total number of confirmed relapses (persistence of neurological symptoms for at least 48 hours confirmed on examination with objective signs).

    • Results showed that patients treated with Copaxone achieved the following clinical and MRI endpoints compared with placebo, respectively:

      • Number of confirmed relapses during the 12-month placebo-controlled phase: adjusted mean estimates – 0.331 vs 0.505 (relative risk reduction, 34%; P <.0001)

      • Cumulative number of new or enlarging T2 lesions at Months 6 and 12: adjusted mean estimates – 3.650 vs 5.592 (relative risk reduction, 35%; P <.0001)

      • Cumulative number of new or enlarging T1-weighted images at Months 6 and 12: adjusted mean estimates – 0.905 vs 1.639 (relative risk reduction, 45%; P <.0001)

    Copaxone Note

    Not Applicable

    Copaxone Patient Counseling

    Patient Counseling

    Optional Autoinjector

    • Advise patients with new or existing glatiramer acetate prescriptions to consult their pharmacist or healthcare provider about using an optional prescribed compatible autoinjector device. Advise patients that not all optional prescribed autoinjectors are compatible with all glatiramer acetate products and using an autoinjector that is not compatible may increase the risk for medication errors, such as missing a dose or administration of a partial dose. 

    Immediate Post-Injection Reaction

    • Advise patients that Copaxone may cause various symptoms after injection, including flushing, chest pain, palpitations, tachycardia, anxiety, dyspnea, constriction of the throat, and urticaria.

    • Inform patients that these symptoms may occur early or may have their onset several months after the initiation of treatment. 

    Chest Pain

    • Advise patients that they may experience transient chest pain either as part of the Immediate Post-Injection Reaction or in isolation. Inform patients that the pain should be transient.

    • Seek medical attention if chest pain of unusual duration or intensity develops.

    Lipoatrophy and Skin Necrosis at Injection Site 

    • Advise patients that localized lipoatrophy, and rarely, skin necrosis may occur at injection sites. Instruct patients to follow proper injection technique and to rotate injection areas and sites with each injection to minimize these risks.

    Hepatic Injury

    • Advise patients that hepatic injury, including hepatic failure and hepatitis with jaundice, has been reported.

    Pregnancy

    • Instruct patients that if they are pregnant or plan to become pregnant while taking Copaxone they should inform their physician.

    Lactation

    • Advise patients to notify their healthcare provider if they are breastfeeding or intend to breastfeed during Copaxone therapy.

    Cost Savings Program

    Copaxone copay and financial support

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