Epoetin alfa injection and epoetin alfa-epbx injection are biologic medications (medications made from living organisms). Biosimilar epoetin alfa-epbx injection is highly similar to epoetin alfa injection and works the same way as epoetin alfa injection in the body. Therefore, the term epoetin injection products will be used to represent these medications in this discussion.

All patients:

Using epoetin alfa injection products increases the risk that blood clots will form in or move to the legs, lungs, or brain. Tell your doctor if you have or have ever had heart disease, a stroke, deep venous thrombosis (DVT; blood clot in your leg), a pulmonary embolus (PE; blood clot in your lungs), or if you are going to have surgery. Before having any surgery, even dental surgery, tell your doctor or dentist that you are being treated with an epoetin alfa injection product, especially if you are having coronary artery bypass graft (CABG) surgery or orthopedic surgery. Your doctor may prescribe an anticoagulant (‘blood thinner’) to prevent clots from forming during surgery. Call your doctor immediately or get emergency medical help if you experience any of the following symptoms: pain, tenderness, redness, warmth, and/or swelling in the legs; coolness or paleness in an arm or leg; difficulty breathing or shortness of breath; chest pain; sudden trouble speaking or understanding speech; sudden confusion; sudden weakness or numbness of an arm or leg (especially on one side of the body) or of the face; sudden trouble walking, dizziness, or loss of balance or coordination; or fainting. If you are being treated with hemodialysis (treatment to remove waste from the blood when the kidneys are not working), a blood clot may form in your vascular access (place where the hemodialysis tubing connects to your body). Tell your doctor if your vascular access is not working as usual.

Your doctor will adjust your dose of an epoetin alfa injection product so that your hemoglobin level (amount of a protein found in red blood cells) is just high enough that you do not need a red blood cell transfusion (transfer of one person’s red blood cells to another person’s body to treat severe anemia). If you receive enough of an epoetin alfa product to increase your hemoglobin to a normal or near normal level, there is a greater risk that you will have a stroke or develop serious or life threatening heart problems including heart attack or heart failure. Call your doctor immediately or get emergency medical help if you experience any of the following symptoms: chest pain, squeezing pressure, or tightness; shortness of breath; nausea, lightheadedness, sweating, and other early signs of heart attack; discomfort or pain in the arms, shoulder, neck, jaw, or back; or swelling of the hands, feet, or ankles.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body’s response to epoetin alfa injection products. Your doctor may decrease your dose or tell you to stop using an epoetin alfa injection product for a period of time if the tests show that you are at high risk of experiencing serious side effects. Follow your doctor’s directions carefully.

Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with an epoetin alfa injection product and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer’s website to obtain the Medication Guide.

Talk to your doctor about the risks of using an epoetin alfa injection product.

Cancer patients:

In clinical studies, people with certain cancers who received epoetin alfa injection died sooner or experienced tumor growth, a return of their cancer, or cancer that spread sooner than people who did not receive the medication. You should only receive epoetin alfa injection products to treat anemia caused by chemotherapy if your chemotherapy is expected to continue for at least 2 months after you start your treatment with epoetin alfa injection and if there is not a high chance that your cancer will be cured. Treatment with epoetin alfa injection products should be stopped when your course of chemotherapy ends.

Surgical patients:

You may be given an epoetin alfa injection product to decrease the risk that you will develop anemia and require a blood transfusion as a result of blood loss during certain types of surgery. However, receiving an epoetin alfa injection product before and after surgery may increase the risk that you will develop a dangerous blood clot during or after surgery. Your doctor will probably prescribe medication to help prevent blood clots.

Epoetin alfa injection products are used to treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure (condition in which the kidneys slowly and permanently stop working over a period of time). Epoetin alfa injection products are also used to treat anemia caused by chemotherapy in people with certain types of cancer or caused by zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). Epoetin alfa injection products are also used before and after certain types of surgery to decrease the chance that blood transfusions (transfer of one person’s blood to another person’s body) will be needed because of blood loss during surgery. Epoetin alfa injection products should not be used to decrease the risk that transfusions will be needed in people who are having surgery on their hearts or blood vessels. Epoetin alfa injection products also should not be used to treat people who are able and willing to donate blood before surgery so that this blood can be replaced in their bodies during or after surgery. Epoetin alfa injection products cannot be used in place of a red blood cell transfusion to treat severe anemia and has not been shown to improve tiredness or poor well-being that may be caused by anemia. Epoetin alfa products are in a class of medications called erythropoiesis-stimulating agents (ESAs). They work by causing the bone marrow (soft tissue inside the bones where blood is made) to make more red blood cells.

Epoetin alfa injection products come as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected one to three times weekly. When epoetin alfa injection products are used to decrease the risk that blood transfusions will be required due to surgery, it is sometimes injected once daily for 10 days before surgery, on the day of surgery and for 4 days after surgery. Alternatively, epoetin alfa injection products are sometimes injected once weekly, beginning 3 weeks before surgery and on the day of surgery.

Your doctor will start you on a low dose of an epoetin alfa injection product and adjust your dose depending on your lab results and how you are feeling, usually not more than once every month. Your doctor may also tell you to stop using an epoetin alfa injection product for a time. Follow these instructions carefully.

Epoetin alfa injection products will help control your anemia only as long as you continue to use it. It may take 2–6 weeks or longer before you feel the full benefit of an epoetin alfa injection product. Do not stop using an epoetin alfa injection product without talking to your doctor.

Epoetin alfa injection products may be given by a doctor or nurse, or you may be told to inject the medication at home. If you will be injecting the medication at home, follow the directions on your prescription label carefully and ask your doctor or pharmacist to explain any part you do not understand. Use an epoetin alfa injection product exactly as directed. To help you remember to use an epoetin alfainjection product, mark a calendar to keep track of when you are to receive a dose. Do not use more or less of it or use it more often than prescribed by your doctor.

If you are using an epoetin alfa injection product at home, a healthcare provider will show you how to inject the medication. Be sure that you understand these directions. Before you use an epoetin alfaproduct for the first time, you and the person who will be giving the injections should read the manufacturer’s information for the patient that comes with it. Ask your healthcare provider if you have any questions about where on your body you should inject the medication, how to give the injection, what type of syringe to use, or how to dispose of used needles and syringes after you inject the medication. Always keep a spare syringe and needle on hand.

Do not shake an epoetin alfa injection product. If you shake the medication, it may look foamy and should not be used.

You can inject an epoetin alfa injection product just under the skin anywhere on the outer area of your upper arms, middle of the front thighs, stomach (except for a 2-inch [5-centimeter] area around the navel [belly button]), or outer area of the buttocks. Do not inject an epoetin alfa injection product into a spot that is tender, red, bruised, hard, or has scars or stretch marks. Choose a new spot each time you inject the medication, as directed by your doctor.

If you are being treated with dialysis (treatment to remove waste from the blood when the kidneys are not working), your doctor may tell you to inject the medication into your venous access port. Ask your doctor if you have any questions about how to inject your medication.

Always look at the solution before you inject it. Be sure that the vial is labeled with the correct name and strength of medication and an expiration date that has not passed. Also check that the solution is clear and colorless and does not contain lumps, flakes, or particles. If there are any problems with your medication, call your pharmacist and do not inject it.

This medication may be prescribed for other uses. Talk to your doctor about the risks of using this medication for your condition.

Before using an epoetin alfa injection product,

• tell your doctor and pharmacist if you are allergic to epoetin alfa, epoetin alfa-epbx, darbepoetin alfa (Aranesp), any other medications, or any of the ingredients in epoetin alfa injection products. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have or have had high blood pressure and if you have ever had pure red cell aplasia (PRCA; a type of severe anemia that may develop after treatment with an ESA such as darbepoetin alfa injection or epoetin alfa injection). Your doctor may tell you not to use an epoetin alfa injection product.
• tell your doctor if you have or have ever had seizures. If you are using an epoetin alfa injection product to treat anemia caused by chronic kidney disease, tell your doctor if you have or have ever had cancer.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using an epoetin alfa injection product, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are using an epoetin alfa injection product.

Your doctor may prescribe a special diet to help control your blood pressure and to help increase your iron levels so that an epoetin alfa injection product can work as well as possible. Follow these directions carefully and ask your doctor or dietician if you have any questions.

Call your doctor to ask what to do if you miss a dose of an epoetin injection product. Do not use a double dose to make up for a missed one.

Epoetin alfa injection products may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• headache
• joint or muscle aches, pain, or soreness
• nausea
• vomiting
• weight loss
• sores in the mouth
• difficulty falling asleep or staying asleep
• depression
• muscle spasms
• runny nose, sneezing, and congestion
• fever, cough, or chills
• redness, swelling, pain, or itching at the injection spot

Some side effects can be serious. If you experience any of the following symptoms, or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:

• rash
• hives
• itching
• swelling of the face, throat, tongue, lips, or eyes
• skin blisters or peeling skin
• wheezing
• difficulty breathing or swallowing
• unusual tiredness
• lack of energy
• dizziness
• fainting
• seizures

Epoetin alfa injection products may cause other side effects. Call your doctor if you have any unusual problems while using this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in to protect from light, tightly closed, and out of reach of children. Store epoetin alfa and epoetin alfa-epbx in the refrigerator, but do not freeze it. Dispose of any medication that has been frozen. Dispose of a multidose vial of epoetin alfa injection 21 days after you first use it.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services at 911.

Symptoms of overdose may include:

• fast or racing heart beat

Keep all appointments with your doctor. Your doctor will monitor your blood pressure often during your treatment with epoetin alfa injection products.

Before having any laboratory test, tell your doctor and the laboratory personnel that you are using an epoetin alfa injection product.

Do not let anyone else use your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

• Epogen^®(Epoetin Alpha)
• Eprex^®(Epoetin Alpha)^¶
• Procrit^® (Epoetin Alpha)
• Retacrit^®(Epoetin Alpha-epbx)

• EPO
• Erythropoietin Human Glycoform alpha (Recombinant)
• rHuEPO-alpha