[Posted 03/14/2013]ISSUE:FDA is evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis and pre-cancerous cellular changes called pancreatic duct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: Web Site
and Web Site
Liraglutide injection may increase the risk that you will develop tumors of the thyroid gland, including medullary thyroid carcinoma (MTC; a type of thyroid cancer), which may cause death if it is not treated at an early stage. If you develop thyroid cancer, your thyroid gland may need to be surgically removed. Tell your doctor if you or anyone in your family has or has ever had thyroid cancer, medullary thyroid carcinoma, or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2; condition that causes tumors in more than one gland in the body). If so, your doctor will probably tell you not to use liraglutide injection. If you experience any of the following symptoms, call your doctor immediately: lump or swelling in the neck; hoarseness; difficulty swallowing; or shortness of breath.
Keep all appointments with your doctor and the laboratory. Your doctor may order certain tests to check your body's response to liraglutide injection.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with liraglutide 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 ( Web Site
) or the manufacturer's website to obtain the Medication Guide.
Talk to your doctor about the risks of using liraglutide injection.
Liraglutide injection is used with a diet and exercise program to control blood sugar levels in adults with type 2 diabetes (condition in which the body does not use insulin normally and therefore cannot control the amount of sugar in the blood) when other medications did not control levels well enough. Liraglutide injection 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) or diabetic ketoacidosis (a serious condition that may develop if high blood sugar is not treated). Liraglutide injection is in a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists. It works by helping the pancreas to release the right amount of insulin when blood sugar levels are high. Insulin helps move sugar from the blood into other body tissues where it is used for energy. Liraglutide injection also slows the emptying of the stomach and may decrease appetite and cause weight loss.
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.
Liraglutide injection comes as a solution (liquid) in a prefilled dosing pen to inject subcutaneously (under the skin) in your stomach, thigh, or upper arm. It is usually injected once a day with or without food. Use liraglutide injection at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use liraglutide injection exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.
Your doctor will probably start you on a low dose of liraglutide injection and increase your dose after one week.
Liraglutide injection controls diabetes but does not cure it. Continue to use liraglutide injection even if you feel well. Do not stop using liraglutide injection without talking to your doctor.
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 liraglutide using the pen. Also make sure you know how and when to set up a new pen, and what to do if you drop your pen. Ask your doctor or pharmacist to show you how to use the pen. Follow the directions carefully.
Always look at your liraglutide solution before you inject it. It should be clear, colorless, and free of particles. Do not use liraglutide 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.
Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
Before using liraglutide injection,
- tell your doctor and pharmacist if you are allergic to liraglutide, any other medications, or any of the ingredients in liraglutide injection. 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. It is especially important to tell your doctor about all the medications you take by mouth because liraglutide may change the way your body absorbs these medications. Also be sure to mention insulin or oral medications for diabetes especially sulfonylureas, including chlorpropamide (Diabinese), glimepiride (Amaryl, in Avandaryl, in Duetact), glipizide (Glucotrol, in Metaglip), glyburide (DiaBeta, in Glucovance, Glycron, Glynase, Micronase), tolazamide, and tolbutamide. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you drink or have ever drunk large amounts of alcohol and if you have or have ever had pancreatitis (inflammation of the pancreas); severe stomach problems, including gastroparesis (slowed movement of food from the stomach to the small intestine) or problems digesting food; a high level of triglycerides (fats) in the blood; gallstones (solid deposits that form in the gallbladder); or kidney or liver disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using liraglutide injection, call your doctor.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are using liraglutide injection.
- ask your doctor what to do if you get sick, develop an infection or fever, experience unusual stress, or are injured. These conditions can affect your blood sugar and the amount of liraglutide you may need.
Be sure to follow all exercise and dietary recommendations made by your doctor or dietitian.
Inject the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not inject a double dose to make up for a missed one.
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.
Liraglutide injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- loss of appetite
- runny nose
- difficulty urinating or pain or burning on urination
- rash or redness in the place where the medication was injected
Some side effects can be serious. If you experience either of these symptoms or those listed in the IMPORTANT WARNING section, stop using liraglutide injection and call your doctor immediately:
- ongoing pain that begins in the upper left or middle of the stomach but may spread to the back
Liraglutide injection 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 [at Web Site] or by phone [1-800-332-1088].
Keep this medication in the container it came in and out of reach of children. Store it away from light and heat. Store unused liraglutide pens in the refrigerator (36°F to 46°F [2°C to 8°C]), but do not place them near the refrigerator cooling element. Once a liraglutide pen is in use, store it at room temperature (59°F to 86°F [15°C to 30°C]) or in the refrigerator. Do not freeze. Do not use liraglutide if it has been frozen or exposed to temperatures above 86°F (30°C). Keep the cap on the liraglutide pen when it is not in use.
When traveling, be sure to keep liraglutide pens dry and at a temperature between 59°F to 86°F (15°C to 30°C).
Make a note of the date you first use a liraglutide pen, and throw away the pen after 30 days, even if there is some solution left in the pen. Throw away any liraglutide pens that are outdated or no longer needed. Talk to your health care provider about the proper disposal of your medication.
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:
- severe nausea
- severe vomiting
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 liraglutide injection. Your doctor will also tell you how to check your response to liraglutide injection by measuring your blood sugar levels at home. Follow these directions carefully.
Before having any laboratory test, tell your doctor and the laboratory personnel that you are using liraglutide 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.
AHFS® Consumer Medication Information. © Copyright, 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.
Selected Revisions: February 15, 2014.