[Posted 06/24/2012] ISSUE: FDA notified healthcare professionals that new, modified recommendations for more conservative dosing of Erythropoiesis-Stimulating Agents (ESAs) in patients with chronic kidney disease (CKD) have been approved to improve the safe use of these drugs. FDA has made these recommendations because of data showing increased risks of cardiovascular events with ESAs in this patient population. The new dosing recommendations are based on clinical trials showing that using ESAs to target a hemoglobin level of greater than 11 g/dL in patients with CKD provides no additional benefit than lower target levels, and increases the risk of experiencing serious adverse cardiovascular events, such as heart attack or stroke.
BACKGROUND: ESAs treat certain types of anemia by stimulating the bone marrow to produce red blood cells and by decreasing the need for blood transfusions. The manufacturer has revised the Boxed Warning, Warnings and Precautions, and Dosage and Administration sections of the labels for the ESAs to include this new information.
RECOMMENDATION: Healthcare professionals should weigh the possible benefits of using ESAs to decrease the need for red blood cell transfusions in CKD patients against the increased risks for serious cardiovascular events, and should inform their patients of the current understanding of potential risks and benefits. Therapy should be individualized to the patient and the lowest possible ESA dose given to reduce the need for transfusions. See the Drug Safety Communication for additional information including a table of key trials and other supporting references. Treatment with ESAs in CKD was discussed at the Drug Safety and Risk Management Advisory Committee, held October 18, 2010. For summary minutes of that Advisory Committee, see the following link: http://goo.gl/dQjYw. For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
All patients:
Epoetin alfa injection increases the risk of blood clots forming in or moving to the legs, lungs, or brain. Call your doctor immediately 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; shortness of breath; cough that won't go away or that brings up blood; chest pain; sudden trouble seeing in one or both eyes; 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; sudden severe headache; or seizures.
Using epoetin alfa injection increases the risk that you will develop a blood clot during or after surgery. Before you have surgery, tell your doctor that you are using epoetin alfa injection. Your doctor may prescribe an anticoagulant ('blood thinner') to help prevent blood clots from forming during or after surgery.
Your doctor will adjust your dose of epoetin alfa injection so that your hemoglobin level (amount of a protein found in red blood cells) is between 10-12 g/dL. If your hemoglobin level is higher than this, there is a greater risk that you will develop serious side effects including heart attack, stroke, heart failure, blood clots, and death. Call your doctor immediately 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; fast or irregular heartbeat; swelling of the hands, feet, or ankles; blue-grey coloring or darkening around mouth or nails; extreme tiredness or weakness; or fainting or loss of consciousness.
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. Your doctor may decrease your dose or tell you to stop using epoetin alfa injection for a period of time if the tests show that you are at high risk of experiencing serious side effects of epoetin alfa injection. 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 epoetin alfa injection 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 epoetin alfa injection.
Patients with chronic kidney failure:
If you are receiving hemodialysis (treatment in which the blood is passed through a filter to remove wastes that would normally be removed by the kidneys), you may develop a blood clot in your vascular access (place on your body where your blood is removed and returned during dialysis). Call your doctor right away if you think you have a blood clot in your vascular access.
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. If you have cancer, there is a risk that your tumor will return, grow faster, or you will die sooner if you receive epoetin alfa injection. To decrease these risks, you should receive the lowest possible dose of epoetin alfa injection and you should only receive epoetin alfa injection when you are receiving chemotherapy to treat your symptoms, rather than to cure your cancer. Treatment with epoetin alfa injection should be stopped when your course of chemotherapy ends.
A program called the ESA APPRISE Oncology Program has been set up to be sure that epoetin alfa injection is used safely. Your doctor will need to complete training and enroll in this program before you can receive epoetin alfa injection. As part of the program, you will receive written information about the risks of using epoetin alfa injection and you will need to sign a form before you receive the medication to show that your doctor has discussed the risks of epoetin alfa injection with you. Your doctor will give you more information about the program and will answer any questions you have about the program and your treatment with epoetin alfa injection.
Epoetin alfa injection is 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 is also used to treat anemia caused by chemotherapy (medications to treat cancer) that is used for at least 2 months or zidovudine (AZT, Retrovir, in Trizivir, in Combivir), a medication used to treat human immunodeficiency virus (HIV). Epoetin alfa injection is also used before and after certain types of surgery to decrease the number of blood transfusions (transfer of one person's blood to another person's body) needed for expected or actual blood loss during surgery. Epoetin alfa is in a class of medications called erythropoiesis-stimulating agents (ESAs). It works by causing the bone marrow (soft tissue inside the bones where blood is made) to make more red blood cells.
Epoetin alfa injection comes 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 is used to prevent and treat anemia 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 is sometimes injected once weekly, beginning 3 weeks before surgery, with a dose also on the day of surgery. To help you remember to use epoetin alfa injection, mark a calendar to keep track of when you are to receive a dose. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use epoetin alfa injection exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.
Your doctor may start you on the lowest possible dose of epoetin alfa injection and gradually increase or decrease your dose, usually not more than once every month. Your doctor may also tell you to stop using epoetin alfa injection for a time. Follow these instructions carefully. If your doctor tells you to stop using epoetin alfa injection, do not begin using it again until your doctor tells you that you should. It is likely that your doctor will restart your treatment with a lower dose of epoetin alfa injection than you were using.
Epoetin alfa injection is used to reduce the need for red blood cell transfusions. It does not cure anemia. It may take up to 2 to 6 weeks of treatment before there is an increase in the number of red blood cells. Do not stop using epoetin alfa injection without talking to your doctor. If you do not respond to treatment with epoetin alfa injection, your doctor may check to see if there is another cause for your anemia.
Epoetin alfa injections are usually given by a doctor or nurse. Your doctor may decide that you can inject epoetin alfa yourself or that you may have a friend or relative give the injections. Your doctor will make sure the person who will be injecting the medication can give the injection correctly. Always follow the instructions of your doctor concerning the dose, how to give the medication, and how often to give the medication. Be sure that you and the person who will be giving the injections read the manufacturer's information for the patient that comes with epoetin alfa injection before you use it for the first time at home.
If you are using epoetin alfa injection at home, you will need to use disposable syringes and needles to inject your medication. Your doctor or pharmacist will tell you what type of syringe you should use. Do not use any other type of syringe because you may not get the right amount of medication. Always keep a spare syringe and needle on hand. Use a disposable syringe or needle only one time. Follow the directions given to you for throwing away the needle and syringe after use.
If your doctor has prescribed epoetin alfa injection in a single use vial, the vial can be used only one time. Do not put a needle through the rubber stopper of the vial more than once. Throw away the vial after you have used it for one dose, even if it is not empty.
Do not shake epoetin alfa injection.
Always inject epoetin alfa in its own syringe; never mix it with any other medication.
If you are injecting epoetin alfa subcutaneously, you can inject it 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), or outer area of the buttocks. Do not inject epoetin alfa into a spot that is tender, red, bruised, hard, or has scars or stretch marks. Choose a new spot each time you inject epoetin alfa, as directed by your doctor. Write down the date, time, dose of epoetin alfa injection, and the spot where you injected your dose in a record book.
Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.
This medication may be prescribed for other uses. Talk to your doctor about the risks of using this medication for your condition.
If you are following a prescribed special diet because you have kidney disease or high blood pressure, follow it carefully, even if you feel better while using epoetin alfa injection. Epoetin alfa injection will not work unless your body has enough iron. Your doctor or dietician will probably tell you to eat foods that are rich in iron. If you cannot get enough iron from your diet, your doctor may prescribe an iron supplement. Take this supplement exactly as directed.
Call your doctor to ask what to do if you miss a dose of epoetin alfa injection. Do not use a double dose to make up for a missed one.
headache
joint or muscle aches, pain, or soreness
nausea
vomiting
indigestion
stomach pain
diarrhea
constipation
difficulty falling asleep or staying asleep
itching
pain, burning, numbness, or tingling in the hands or feet
redness, swelling, pain, or itching at the injection spot
fever, sore throat, chills, cough, and other signs of infection
spreading rash over the whole body
hives
swelling of the face, throat, tongue, lips, eyes
wheezing
difficulty breathing or swallowing
hoarseness
lack of energy
feeling cold most of the time
Epoetin alfa injection may cause other side effects. Call your doctor if you have any unusual problems while taking 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 [at http://www.fda.gov/Safety/MedWatch] or by phone [1-800-332-1088].
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it in the refrigerator, but do not freeze it. Once a vial has been taken out of its carton, keep it covered to protect it from room light until the dose is given. Throw away any medication that is outdated or no longer needed. Throw away a multidose vial of epoetin alfa injection 21 days after you first use it. Talk to your pharmacist about the proper disposal of your medication.
When traveling, place epoetin alfa injection in its original box in an insulated cooler with coolant such as blue ice. Do not place epoetin alfa vials directly on ice or coolants, and do not allow them to freeze. If a vial does freeze, do not use it. Once you arrive, place the medication in a refrigerator as soon as possible.
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
pain, tenderness, redness, warmth, and/or swelling in the legs
chest pain, squeezing pressure, or tightness
discomfort or pain in the arms, shoulder, neck, jaw, or back
fast or irregular heartbeat
shortness of breath
cough that won't go away or coughing up blood
swelling of the hands, feet, or ankles
blue-grey color or darkening around mouth or nails
excessive sweating
dizziness or lightheadedness
fainting or loss of consciousness
sudden trouble seeing in one or both eyes
sudden confusion
sudden trouble speaking or understanding speech
sudden weakness or numbness of an arm or leg (especially on one side of the body) or face
sudden trouble walking or loss of balance or coordination
sudden severe headache
extreme tiredness or weakness
seizure
increased blood pressure
blood clot in hemodialysis port
Before having any laboratory test, tell your doctor and the laboratory personnel that you are using epoetin alfa injection.
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.
Last Reviewed - 04/15/2012
AHFS® Consumer Medication Information. © Copyright, 2012. The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.