(ex en' a tide)
[Posted 03/14/2013] ISSUE: FDA is evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis and pre-cancerous cellular changes called pancreatic duct metaplasia in patients with type 2 diabetes treated with a class of drugs called incretin mimetics. These findings were based on examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes. FDA has asked the researchers to provide the methodology used to collect and study these specimens and to provide the tissue samples so the Agency can further investigate potential pancreatic toxicity associated with the incretin mimetics.
BACKGROUND: Drugs in the incretin mimetic class include exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto). These drugs work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal. They are used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.
RECOMMENDATIONS: FDA has not reached any new conclusions about safety risks with incretin mimetic drugs. This early communication is intended only to inform the public and health care professionals that the Agency intends to obtain and evaluate this new information. FDA will participate in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Cancer Institute's (NCI) Workshop on Pancreatitis-Diabetes-Pancreatic Cancer in June 2013 to gather and share additional information. FDA will communicate its final conclusions and recommendations when its review is complete or when the Agency has additional information to report.
The Warnings and Precautions section of drug labels and patient Medication Guides for incretin mimetics contain warnings about the risk of acute pancreatitis. FDA has not previously communicated about the potential risk of pre-cancerous findings of the pancreas with incretin mimetics. FDA has not concluded these drugs may cause or contribute to the development of pancreatic cancer.
At this time, patients should continue to take their medicine as directed until they talk to their health care professional, and health care professionals should continue to follow the prescribing recommendations in the drug labels. For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety .
WHY is this medicine prescribed?
Exenatide is used along with diet and exercise to treat type 2 diabetes (condition in which the body does not use insulin normally and therefore cannot control the amount of sugar in the blood). Exenatide is in a class of medications called incretin mimetics. It works by stimulating the pancreas to secrete insulin when blood sugar levels are high. Insulin helps move sugar from the blood into other body tissues where it is used for energy. Exenatide also slows the emptying of the stomach and causes a decrease in appetite. Exenatide is not used to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar in the blood). Exenatide is not used instead of insulin to treat people with diabetes who need insulin.
Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems. Using medication(s), making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye problems, including changes or loss of vision, or gum disease. Your doctor and other healthcare providers will talk to you about the best way to manage your diabetes.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with exenatide 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) to obtain the Medication Guide.
HOW should this medicine be used?
Exenatide comes as a solution (liquid) in a prefilled dosing pen to inject subcutaneously (under the skin). It is usually injected twice a day within 60 minutes before the morning and evening meals. Exenatide should not be injected after meals. Your doctor will probably start you on a low dose of exenatide and may switch you to a pen with a higher dose of medication if your blood sugar control has not improved after you have used exenatide for 1 month. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use exenatide injection exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.
Exenatide controls diabetes but does not cure it. Continue to use exenatide even if you feel well. Do not stop using exenatide without talking to your doctor.
Exenatide comes in prefilled dosing pens that contain enough medication for 60 doses (two doses a day for 1 month). You will need to buy needles separately. Ask your doctor or pharmacist what type of needles you will need to inject your medication. Be sure to read and understand the manufacturer's instructions for injecting exenatide using the pen. Also make sure you know how and when to set up a new pen. Ask your doctor or pharmacist to show you how to use the pen. Follow the directions carefully. Never remove the cartridge from the pen or attempt to add any other type of medication to the cartridge.
Always look at your exenatide solution before you inject it. It should be as clear, colorless, and fluid as water. Do not use exenatide if it is colored, cloudy, thickened, or contains solid particles, or if the expiration date on the bottle has passed.
Never reuse needles and never share needles or pens. Always remove the needle right after you inject your dose. Throw away needles in a puncture-resistant container. Ask your doctor or pharmacist how to dispose of the puncture resistant container.
Exenatide can be administered in the thigh (upper leg), abdomen (stomach), or upper arm. Use a different site for each injection, about 1 inch (2.5 centimeters) away from the previous injection but in the same general area (for example, the thigh). Use all available sites in the same general area before switching to a different area (for example, the upper arm). Do not use the same injection site more often than once every month.
Are there OTHER USES for this medicine?
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What SPECIAL PRECAUTIONS should I follow?
Before using exenatide injection,
- tell your doctor and pharmacist if you are allergic to exenatide or any other medications.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril, (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik); diuretics ('water pills'); aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn); medications for high blood pressure; sulfonylureas such as chlorpropamide (Diabinese), glimepiride (Amaryl), glipizide (Glucotrol), glyburide (DiaBeta, Micronase), tolazamide, and tolbutamide; and warfarin (Coumadin).
- if you are taking oral contraceptives (birth control pills) or antibiotics, take them at least 1 hour before you use exenatide injection. If you have been told to take these medications with food, take them with a meal or snack at a time when you do not use exenatide.
- tell your doctor if you drink or have ever drunk large amounts of alcohol, and if you are experiencing nausea, vomiting, and diarrhea or think you may be dehydrated, or if you develop these symptoms at any time during your treatment. Also tell your doctor if you have or have ever had pancreatitis (swelling of the pancreas), gallstones (solid deposits that form in the gallbladder), a high level of triglycerides (fats) in the blood; severe stomach problems; high blood pressure; or kidney disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using exenatide, call your doctor.
- ask your doctor about the safe use of alcoholic beverages while you are taking exenatide.
What SPECIAL DIETARY instructions should I follow?
Be sure to follow all exercise and dietary recommendations made by your doctor or dietitian. It is important to eat a healthy diet.
What should I do IF I FORGET to take a dose?
Skip the missed dose and continue your regular dosing schedule. Do not inject a double dose to make up for a missed one.
What SIDE EFFECTS can this medicine cause?
This medication may cause changes in your blood sugar. You should know the symptoms of low and high blood sugar and what to do if you have these symptoms.
Exenatide injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- jittery feeling
- acid stomach
- weight loss
Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:
- ongoing pain that begins in the upper left or middle of the stomach but may spread to the back
- difficulty breathing or swallowing
- swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
- changes in the color or amount of urine
- urinating more or less often than usual
- swelling of the arms, hands, feet, ankles, or lower legs
- excessive tiredness
- changes in appetite or digestion
- dull ache in the mid to lower back
Exenatide may cause other side effects. Call your doctor if you have any unusual problems while using this medication.
What should I know about STORAGE and DISPOSAL of this medication?
Store unused exenatide pens in their original carton in the refrigerator protected from light. Once in use, store exenatide pens at room temperature (up to 77°F [25°C]) protected from light. Do not freeze. Do not use exenatide if it has been frozen. Do not store exenatide pens with the needle attached. Keep exenatide pens out of the reach of children.
When traveling, be sure to keep exenatide pens dry. Unused pens should be refrigerated or kept at a cold temperature between 36°F to 46°F (2°C to 8°C). Pens that are in use can be stored at room temperature up to 77°F (25°C) (not in a car glove compartment or other hot place).
Make a note of the date you first use an exenatide pen, and throw away the pen after 30 days, even if there is some solution left in the pen. Throw away any exenatide pens that are outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
What should I do in case of OVERDOSE?
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.
Symptoms of overdose may include the following:
- severe upset stomach
- severe vomiting
- symptoms of hypoglycemia
What OTHER INFORMATION should I know?
Keep all appointments with your doctor and the laboratory. Your blood sugar and glycosylated hemoglobin (HbA1c) should be checked regularly to determine your response to exenatide. Your doctor will also tell you how to check your response to this medication by measuring your blood or urine sugar levels at home. Follow these instructions carefully.
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.