Copaxone

GENERIC AVAILABLE: Yes

>10%

Injection site pain (73%)

Injection site erythema (66%)

Injection site inflammation (49%)

Weakness (41%)

Injection site pruritus (40%)

Injection site mass (27%)

Vasodilation (27%)

Pain (28%)

Arthralgia (24%)

Anxiety (23%)

Hypertonia (22%)

Nausea (22%)

Flu syndrome (19%)

Dyspnea (19%)

Pruritus (18%)

Rash (18%)

Palpitations (17%)

Chest pain (13-16% 20 mg/day; 2-4% 40 mg 3x/wk)

Injection site induration (13%)

Diarrhea (12%)

Lymphadenopathy (12%)

Injection site welt (11%)

1-10%

Injection site pain/inflammation (10%)

Anorexia (8%)

Frequency Not Defined

Anxiety

Arthralgia

Asthenia

Hypertonia

Infection

Pain

Postmarketing Reports

Cardiovascular system: Thrombosis; peripheral vascular disease; pericardial effusion; myocardial infarct; deep thrombophlebitis; coronary occlusion; congestive heart failure; cardiomyopathy; cardiomegaly; arrhythmia; angina pectoris

Digestive system: tongue edema; stomach ulcer; hemorrhage; liver function abnormality; liver damage; hepatitis; eructation; cirrhosis of the liver; cholelithiasis

Hemic and lymphatic system: Thrombocytopenia; lymphoma-like reaction; acute leukemia

Metabolic and nutritional disorders: Hypercholesterolemia

Musculoskeletal system: Rheumatoid arthritis; generalized spasm

Nervous system: Myelitis; meningitis; CNS neoplasm; cerebrovascular accident; brain edema; abnormal dreams; aphasia; convulsion; neuralgia

Respiratory system: Pulmonary embolus; pleural effusion; carcinoma of lung

Special Senses: Glaucoma; blindness

Urogenital system: Urogenital neoplasm; urine abnormality; ovarian carcinoma; nephrosis; kidney failure; breast carcinoma; bladder carcinoma; urinary frequency

Dosage Forms And Strengths

• Injection: 20 mg per mL in a single-dose, prefilled syringe with a white plunger. For subcutaneous use only.
• Injection: 40 mg per mL in a single-dose, prefilled syringe with a blue plunger. For subcutaneous use only.

Storage And Handling

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 (NDC 68546-317-30).

40 mg per mL in a single-dose, prefilled syringe with a blue plunger, in individual blister packages supplied in 12-count cartons (NDC 68546-325-12).

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.

Marketed by: Teva Neuroscience, Inc., Overland Park, KS 66211. Distributed by: Teva Pharmaceuticals USA, Inc., North Wales, PA 19454. Revised: Aug 2016

COPAXONE
(co-PAX-own)
(glatiramer acetate) Injection for Subcutaneous Use

Read this Patient Information before you start using COPAXONE and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.

What is COPAXONE?

COPAXONE is prescription medicine used for the treatment of people with relapsing forms of multiple sclerosis (MS).

It is not known if COPAXONE is safe and effective in children under 18 years of age.

Who should not use COPAXONE?

• Do not use COPAXONE if you are allergic to glatiramer acetate, mannitol or any of the ingredients in COPAXONE. See the end of this leaflet for a complete list of the ingredients in COPAXONE.

What should I tell my doctor before using COPAXONE?

Before you use COPAXONE, tell your doctor if you:

• are pregnant or plan to become pregnant. It is not known if COPAXONE will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if COPAXONE passes into your breast milk. Talk to your doctor about the best way to feed your baby while using COPAXONE.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

COPAXONE may affect the way other medicines work, and other medicines may affect how COPAXONE works.

Know the medicines you take. Keep a list of your medicines with you to show your doctor and pharmacist when you get a new medicine.

How should I use COPAXONE?

• For detailed instructions, see the Instructions for Use at the end of this leaflet for complete information on how to use COPAXONE.
• Your doctor will tell you how much COPAXONE to use and when to use it.
• COPAXONE is given by injection under your skin (subcutaneously).
• Use COPAXONE exactly as your doctor tells you to use it.
• Since every body type is different, talk with your doctor about the injection areas that are best for you.
• You should receive your first dose of COPAXONE with a doctor or nurse present. This might be at your doctor's office or with a visiting home health nurse who will teach you how to give your COPAXONE injections.

What are the possible side effects of COPAXONE?

COPAXONE may cause serious side effects, including:

• Post-Injection Reactions. Serious side effects may happen right after you inject COPAXONE at any time during your course of treatment. Call your doctor right away if you have any of these post-injection reaction symptoms including:
  • redness to your cheeks or other parts of the body (flushing)
  • chest pain
  • fast heart beat
  • anxiety
  • breathing problems or tightness in your throat
  • swelling, rash, hives, or itching

If you have symptoms of a post-injection reaction, do not give yourself more injections until a doctor tells you to.

• Chest Pain. You can have chest pain as part of a post-injection reaction or by itself. This type of chest pain usually lasts a few minutes and can begin around 1 month after you start using COPAXONE. Call your doctor right away if you have chest pain while using COPAXONE.
• Damage to your skin. Damage to the fatty tissue just under your skin's surface (lipoatrophy) and, rarely, death of your skin tissue (necrosis) can happen when you use COPAXONE. Damage to the fatty tissue under your skin can cause a “dent” at the injection site that may not go away. You can reduce your chance of developing these problems by:
  • following your doctor's instructions for how to use COPAXONE
  • choosing a different injection area each time you use COPAXONE. See Step 4 in the Instructions for Use, “Choose your injection area”.

The most common side effects of COPAXONE include:

• skin problems at your injection site including:
  • redness
  • pain
  • swelling
  • itching
  • lumps
• rash
• shortness of breath
• flushing (vasodilation)

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of COPAXONE. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store COPAXONE?

• Store COPAXONE in the refrigerator between 36°F to 46°F (2°C to 8°C).
• When you are not able to refrigerate COPAXONE, you may store it for up to 1 month at room temperature between 59°F to 86°F (15°C to 30°C).
• Protect COPAXONE from light or high temperature.
• Do not freeze COPAXONE syringes. If a syringe freezes, throw it away in a sharps disposal container. See Step 13 in the Instructions for Use, “Dispose of your needles and syringes”.

Keep COPAXONE and all medicines out of the reach of children.

General information about the safe and effective use of COPAXONE.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use COPAXONE for a condition for which it was not prescribed. Do not give COPAXONE to other people, even if they have the same symptoms as you have. It may harm them.

This Patient Information Leaflet summarizes the most important information about COPAXONE. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about COPAXONE that is written for health professionals.

For more information, go to www.copaxone.com or call 1-800-887-8100.

What are the ingredients in COPAXONE?

Active ingredient: glatiramer acetate

Inactive ingredients: mannitol

Instructions for Use

COPAXONE
(co-PAX-own)
(glatiramer acetate) Injection for Subcutaneous Use

For subcutaneous injection only.

Do not inject COPAXONE in your veins (intravenously).

Do not re-use your COPAXONE prefilled syringes.

Do not share your COPAXONE prefilled syringes with another person.

You may give another person an infection or get an infection from them.

You should receive your first dose of COPAXONE with a doctor or nurse present. This might be at your doctor's office or with a visiting home health nurse who will show you how to give your own injections. COPAXONE comes in either a 20 mg Prefilled Syringe with needle attached or a 40 mg Prefilled Syringe with needle attached. How often a dose is given depends on the product strength that is prescribed. Your doctor will prescribe the correct dose for you.

Instructions for Using Your COPAXONE 20 mg Prefilled Syringe:

• COPAXONE 20 mg is injected 1 time each day, in the fatty layer under your skin (subcutaneously).
• Each COPAXONE 20 mg prefilled syringe is for single use (1 time use) only.
• The COPAXONE 20 mg dose is packaged in boxes of 30 prefilled syringes with needles attached. COPAXONE 20 mg prefilled syringes have white plungers.

Instructions for Using Your COPAXONE 40 mg Prefilled Syringe:

• COPAXONE 40 mg is injected 3 times each week, in the fatty layer under your skin (subcutaneously).
• COPAXONE 40 mg should be given on the same 3 days each week, if possible for example, Monday, Wednesday, and Friday. Give your COPAXONE injections at least 48 hours (2 days) apart.
• Each COPAXONE 40 mg prefilled syringe is for single use (1 time use) only.
• The COPAXONE 40 mg dose is packaged in boxes of 12 prefilled syringes with needles attached. COPAXONE 40 mg prefilled syringes have blue plungers.

How do I inject COPAXONE?

Step 1: Gather the supplies you will need to inject COPAXONE. See Figure A.

• 1 blister pack with a COPAXONE Prefilled Syringe with needle attached
• Alcohol wipe (not supplied)
• Dry cotton ball (not supplied)
• A place to record your injections, like a notebook (not supplied)
• Sharps disposal container (not supplied). See Step 13 below, “Dispose of your needles and syringes”.

Figure A

Step 2: Remove only 1 blister pack from the COPAXONE prefilled syringe carton. See Figure B.

Figure B

• Place the supplies you will need on a clean, flat surface in a welllit area.
• After you remove 1 blister pack from the carton, keep all unused syringes in the carton and store them in the refrigerator.
• Let the blister pack, with the syringe inside, warm to room temperature for about 20 minutes.
• Wash your hands. Be careful not to touch your face or hair after washing your hands.

Step 3: Look closely at your COPAXONE prefilled syringe.

• There may be small air bubbles in the syringe. Do not try to push the air bubble from the syringe before giving your injection so you do not lose any medicine.
• Check the liquid medicine in the syringe before you give your injection. The liquid in the syringe should look clear, and colorless, and may look slightly yellow. If the liquid is cloudy or contains any particles, do not use the syringe and throw it away in a sharps disposal container. See Step 13 below, “Dispose of your needles and syringes.”

Step 4: Choose your injection area. See Figure C.

See the injection areas you should use on your body. Talk with your doctor about the injection areas that are best for you.

• The possible injection areas on your body include (See Figure C):
  • your stomach area (abdomen) around the belly button
  • the back of your upper arms
  • upper hips (below your waist)
  • your thighs (above your knees)

Figure C

• For each COPAXONE dose, choose a different injection area from 1 of the areas shown above. See Figure C.
• Do not stick the needle in the same place (site) more than 1 time each week. Each injection area contains multiple injection sites for you to choose from. Avoid injecting in the same site over and over again.
• Keep a record of the sites where you give your injection each day so you will remember where you already injected.

Step 5: Prepare to give your injection.

• There are some injection areas on your body that are hard to reach (like the back of your arm). You may need help from someone who has been instructed on how to give your injection if you cannot reach certain injection areas.
• Do not inject in sites where the skin has scarring or “dents”. Using scarred or dented skin for your injections may make your skin worse.

Step 6: Clean your injection site.

• Clean the injection site using the alcohol wipe and allow your skin to air dry. See Figure D.

Figure D

Step 7: Pick up the syringe with 1 hand and hold it like a pencil. Remove the needle cover with your other hand and set it aside. See Figure E.

Figure E

Step 8: Pinch about a 2 inch fold of skin between your thumb and index finger. See Figure F.

Figure F

Step 9: Giving your injection.

• Rest the heel of your hand holding the syringe against your skin at the injection site. Insert the needle at a 90 degree angle straight into your skin. See Figure G.

Figure G

• When the needle is all the way into your skin, release the fold of skin. See Figure H.

Figure H

Step 10: Give your COPAXONE injection.

To inject the medicine, hold the syringe steady and slowly push down the plunger. See Figure I.

Figure I

Step 11: Remove the needle.

After you have injected all of the medicine, pull the needle straight out. See Figure J.

Figure J

Step 12: Use a clean, dry cotton ball to gently press on the injection site for a few seconds. Do not rub the injection site or re-use the needle or syringe. See Figure K.

Figure K

Step 13: Dispose of your needles and syringes.

• Put your used needles and syringes in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and syringes in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • upright and stable during use,
  • leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Figure L

This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.

Keep the Copaxone pre-filled syringe carton in the refrigerator, out of the reach of children.

The Copaxone package should be refrigerated as soon as you get it, at 36-46°F (2-8°C). If you cannot store Copaxone in a refrigerator, you can store it at room temperature, 59-86°F(15-30°C), for up to one month. Do not store Copaxone at room temperature for longer than one month. Do not freeze Copaxone. If a Copaxone pre-filled syringe freezes, throw it away in a proper container.

Copaxone is light sensitive. Protect it from light when not injecting. Do not use the pre-filled syringe if the solution contains particles or is cloudy.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

In the U.S.

• Copaxone
• Glatopa

Available Dosage Forms:

• Solution
• Powder for Solution
• Kit

Therapeutic Class: Central Nervous System Agent

• It is used to lower the number of setbacks with MS (multiple sclerosis).

Copaxone is contraindicated in patients with known hypersensitivity to glatiramer acetate or mannitol.

Interactions between Copaxone and other drugs have not been fully evaluated. Results from existing clinical trials do not suggest any significant interactions of Copaxone with therapies commonly used in MS patients, including the concurrent use of corticosteroids for up to 28 days. Copaxone has not been formally evaluated in combination with interferon beta.

Evidence supporting the effectiveness of Copaxone derives from five 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 three times per week.

Copaxone 20 mg per mL per day

Study 1 was performed at a single center. Fifty patients were enrolled and randomized to receive daily doses of either Copaxone, 20 mg per mL subcutaneously, or placebo (Copaxone: n=25; placebo: n=25). Patients were diagnosed with RRMS by standard criteria, and had had at least 2 exacerbations during the 2 years immediately preceding enrollment. Patients were ambulatory, as evidenced by a score of no more than 6 on the Kurtzke Disability Scale Score (DSS), a standard scale ranging from 0–Normal to 10–Death due to MS. A score of 6 is defined as one at which a patient is still ambulatory with assistance; a score of 7 means the patient must use a wheelchair.

Patients were examined every 3 months for 2 years, as well as within several days of a presumed exacerbation. To confirm an exacerbation, a blinded neurologist had to document objective neurologic signs, as well as document the existence of other criteria (e.g., the persistence of the neurological signs for at least 48 hours).

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.

Table 3 presents the values of the three outcomes described above, as well as several protocol-specified secondary measures. These values are based on the intent-to-treat population (i.e., all patients who received at least 1 dose of treatment and who had at least 1 on-treatment assessment):

*Progression was defined as an increase of at least 1 point on the DSS, persisting for at least 3 consecutive months.

Study 2 was a multicenter trial of similar design which was performed in 11 US centers. A total of 251 patients (Copaxone: n=125; placebo: n=126) were enrolled. The primary outcome measure was the Mean 2-Year Relapse Rate. Table 4 presents the values of this outcome for the intent-to-treat population, as well as several secondary measures:

In both studies, Copaxone exhibited a clear beneficial effect on relapse rate, and it is based on this evidence that Copaxone is considered effective.

In Study 3, 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. Patients were followed for up to three years or until they reached the primary endpoint. Secondary outcomes were brain MRI measures, including number of new T2 lesions and T2 lesion volume.

Time to development of a second exacerbation was significantly delayed in patients treated with Copaxone compared to placebo (Hazard Ratio = 0.55; 95% confidence interval 0.40 to 0.77; Figure 1). 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.

Figure 1: Time to Second Exacerbation

Patients treated with Copaxone demonstrated fewer new T2 lesions at the last observation (rate ratio 0.41; confidence interval 0.28 to 0.59; p < 0.0001). Additionally, baseline-adjusted T2 lesion volume at the last observation was lower for patients treated with Copaxone (ratio of 0.89; confidence interval 0.84 to 0.94; p = 0.0001).

Study 4 was a multinational study in which MRI parameters were used both as primary and secondary endpoints. A total of 239 patients with RRMS (Copaxone: n=119; and placebo: n=120) were randomized. Inclusion criteria were similar to those in the second study with the additional criterion that patients had to have at least one Gd-enhancing lesion on the screening MRI. The patients were treated in a double-blind manner for nine months, during which they underwent monthly MRI scanning. The primary endpoint for the double-blind phase was the total cumulative number of T1 Gd-enhancing lesions over the nine months. Table 5 summarizes the results for the primary outcome measure monitored during the trial for the intent-to-treat cohort.

Figure 2 displays the results of the primary outcome on a monthly basis.

Figure 2: Median Cumulative Number of Gd-Enhancing Lesions

Copaxone 40 mg per mL three times per week

Study 5 was a double-blind, placebo-controlled, multinational study with a total of 1404 patients with RRMS randomized in a 2:1 ratio to receive either Copaxone 40 mg per mL (n=943) or placebo (n=461) three times a week for 12 months. Patients 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. Baseline EDSS scores ranged from 0 to 5.5 with a median of 2.5. Neurological evaluations were performed at baseline, every three months, and at unscheduled visits for suspected relapse or early termination. MRI was performed at baseline, months 6 and 12, or early termination. A total of 91% of those assigned to Copaxone and 93% of those assigned to placebo completed treatment at 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). The effect of Copaxone on several magnetic resonance imaging (MRI) variables, including number of new or enlarging T2 lesions and number of enhancing lesions on T1-weighted images, was also measured at months 6 and 12.

Table 6 presents the results for the intent-to-treat population.

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

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.