[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:
Darbepoetin 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 darbepoetin 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 darbepoetin 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 darbepoetin 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 darbepoetin alfa injection. Your doctor may decrease your dose or tell you to stop using darbepoetin alfa injection 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 darbepoetin alfa 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 darbepoetin 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 darbepoetin 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 darbepoetin alfa injection. To decrease these risks, you should receive the lowest possible dose of darbepoetin alfa injection and you should only receive darbepoetin alfa injection when you are receiving chemotherapy to treat your symptoms, rather than to cure your cancer. Treatment with darbepoetin 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 darbepoetin alfa injection is used safely. Your doctor will need to complete training and enroll in this program before you can receive darbepoetin alfa injection. As part of the program, you will receive written information about the risks of using darbepoetin 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 darbepoetin 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 darbepoetin alfa injection.
Darbepoetin 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). Darbepoetin alfa injection is also used to treat anemia caused by chemotherapy (medications to treat cancer). Darbepoetin 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.
Darbepoetin alfa injection comes as a solution (liquid) to inject subcutaneously (just under the skin) or intravenously (into a vein). It is usually injected once a week every 1-3 weeks. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use darbepoetin 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 darbepoetin alfa injection and gradually increase or decrease your dose, not more than once every month. Your doctor may also tell you to stop using darbepoetin alfa injection for a time. Follow these instructions carefully. If your doctor tells you to stop using darbepoetin 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 darbepoetin alfa injection than you were using.
Darbepoetin alfa injection is used to reduce the need for red blood cell transfusions. Darbepoetin alfa injection controls anemia but does not cure it. It may take 2-6 weeks or longer before you feel the full benefit of darbepoetin alfa injection. Continue to use darbepoetin alfa injection even if you feel well. Do not stop using darbepoetin alfa injection without talking to your doctor.
Darbepoetin alfa injections are usually given by a doctor or nurse. Your doctor may decide that you can inject darbepoetin alfa yourself, or that you may have a friend or relative give the injections. Your doctor will train the person who will be injecting the medication and will test him to be sure he can give the injection correctly. Be sure that you and the person who will be giving the injections know the correct 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 darbepoetin alfa injection before you use it for the first time at home.
Darbepoetin alfa injection comes in prefilled syringes, a prefilled automatic injection device, and also in vials to use with disposable syringes. Use vials, prefilled automatic injection devices, and prefilled or disposable syringes only once. Do not put a needle through the rubber stopper of a vial more than once. Follow the directions given to you for throwing away the needle and syringe after use.
If you are using vials of darbepoetin alfa injection, you will need to use disposable syringes 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.
Do not shake darbepoetin alfa injection.
Always inject darbepoetin alfa in its own syringe; never mix it with any other medication.
If you are using darbepoetin alfa vials or prefilled syringes subcutaneously, you can inject it just under the skin anywhere on these parts of your body: the outer area of your upper arms, your stomach except for the 2-inch (5-centimeter) area around your navel (belly button), the front of your middle thighs, and the upper outer areas of your buttocks. If you are using darbepoetin alfa prefilled automatic injection device, you can inject it just under the skin on the outer area of your upper arms or the front of your middle thighs; or if your doctor says it is ok, you can also use your stomach except for the 2-inch (5-centimeter) area around your navel (belly button).
Choose a new spot each time you inject darbepoetin alfa. Do not inject darbepoetin alfa into a spot that is tender, red, bruised, hard, or has scars or stretch marks.
Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient. Carefully read this information and be sure to ask your pharmacist or doctor if you have any questions about how to prepare or inject this medication.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
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 darbepoetin alfa injection. Darbepoetin 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 darbepoetin alfa injection. Do not use a double dose to make up for a missed one.
headache
nausea
vomiting
stomach pain
diarrhea
constipation
body, joint, or muscle aches
redness, swelling, bruising, itching, or a lump at the spot where you injected darbepoetin alfa
rash over the whole body
itching
difficulty breathing or swallowing
wheezing
hoarseness
swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
dry mouth
sunken eyes
decreased urination
fever, sore throat, chills, cough, and other signs of infection
feeling cold most of the time
pale skin
Darbepoetin alfa injection may cause other side effects. Call your doctor if you have any unusual problems or you do not feel well 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 [at http://www.fda.gov/Safety/MedWatch] or by phone [1-800-332-1088].
Keep this medication in the carton it came in, tightly closed, and out of reach of children. Once a vial, prefilled automatic injection device, or prefilled syringe has been taken out of its carton, keep it covered to protect it from room light until the dose is given. Store darbepoetin alfa injection in the refrigerator, but do not freeze it. Throw away any medication that has been frozen or is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
When traveling, pack darbepoetin alfa injection in its original carton in an insulated container with a coolant such as blue ice. To avoid freezing, make sure the darbepoetin alfa vial, prefilled automatic injection device, or prefilled syringe does not touch the coolant. Once you arrive, place darbepoetin alfa injection 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.
unusual tiredness, weakness, or lack of energy
shortness of breath
cough that won't go away, or coughing up blood
wheezing
dizziness or lightheadedness
swelling around the mouth or eyes
blue-grey coloring or darkening around mouth or nails
fast or irregular heartbeat
sweating
seizure
fainting or loss of consciousness
chest pain, squeezing pressure, or tightness
discomfort or pain in the arms, shoulder, neck, jaw, or back
nausea
vomiting
sudden weakness or numbness of an arm or leg (especially on one side of the body) or face
sudden confusion
sudden trouble speaking or understanding speech
sudden trouble seeing in one or both eyes
sudden trouble walking, or loss of balance or coordination
sudden severe headache
pain, tenderness, redness, warmth, and/or swelling in the legs
swelling of the hands, feet, or ankles
increased blood pressure
blood clot in hemodialysis access port
Before having any laboratory test, tell your doctor and the laboratory personnel that you are using darbepoetin 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.