AUDIENCE: Pharmacy, Internal Medicine, Patient, Endocrinology
ISSUE: An FDA safety review has found that type 2 diabetes medicines containing saxagliptin and alogliptin may increase the risk of heart failure, particularly in patients who already have heart or kidney disease. As a result, FDA is adding new warnings to the drug labels about this safety issue.
This Communication is an update to the 02/11/2014 FDA Drug Safety Communication.
BACKGROUND: Saxagliptin and alogliptin are part of the class of dipeptidyl peptidase-4 (DPP-4) inhibitor drugs, which are used with diet and exercise to lower blood sugar in adults with type 2 diabetes.
FDA evaluated two large clinical trials conducted in patients with heart disease. These clinical trials were also discussed at the FDA Endocrinologic and Metabolic Drugs Advisory Committee meeting in April 2015. Each trial showed that more patients who received saxagliptin- or alogliptin-containing medicines were hospitalized for heart failure compared to patients who received an inactive treatment called a placebo (see Data Summary in the FDA Drug Safety Communication for additional information). In the saxagliptin trial, 3.5% of patients who received the drug were hospitalized for heart failure versus 2.8% of patients who received a placebo. This is the same as 35 out of every 1,000 patients compared to 28 out of every 1,000 patients. Risk factors included a history of heart failure or kidney impairment. In the alogliptin trial, 3.9% of alogliptin-treated patients were hospitalized for heart failure versus 3.3% in the placebo group. This is the same as 39 out of every 1,000 patients compared to 33 out of every 1,000 patients.
RECOMMENDATION: Health care professionals should consider discontinuing medications containing saxagliptin and alogliptin in patients who develop heart failure and monitor their diabetes control. If a patient's blood sugar level is not well-controlled with their current treatment, other diabetes medicines may be required.
Patients taking these medicines should contact their health care professionals right away if they develop signs and symptoms of heart failure such as:
- Unusual shortness of breath during daily activities
- Trouble breathing when lying down
- Tiredness, weakness, or fatigue
- Weight gain with swelling in the ankles, feet, legs, or stomach
Patients should not stop taking their medicine without first talking to their health care professionals.
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 medication prescribed?
Saxagliptin is used along with diet and exercise to lower blood sugar levels in patients with type 2 diabetes (condition in which blood sugar is too high because the body does not produce or use insulin normally). Saxagliptin is in a class of medications called dipeptidyl peptidase-4 (DPP-4) inhibitors. It works by increasing the amount of insulin produced by the body after meals when blood sugar is high. Saxagliptin 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).
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. Taking 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.
How should this medicine be used?
Saxagliptin comes as a tablet to take by mouth. It is usually taken once a day with or without food. Take saxagliptin 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. Take saxagliptin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Saxagliptin controls type 2 diabetes but does not cure it. Continue to take saxagliptin even if you feel well. Do not stop taking saxagliptin without talking to your doctor.
Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.
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 taking saxagliptin,
- tell your doctor and pharmacist if you are allergic to saxagliptin, any other medications, or any of the ingredients in saxagliptin tablets. 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. Be sure to mention any of the following: certain antifungal medications such as itraconazole (Sporanox) and ketoconazole (Nizoral); clarithromycin (Biaxin); certain medications for HIV (human immunodeficiency virus) or AIDS (acquired immunodeficiency syndrome) such as atazanavir (Reyataz), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Invirase); insulin or oral medications for diabetes such as acetohexamide, chlorpropamide (Diabinese), glimepiride (Amaryl, in Avandaryl), glipizide (Glucotrol, in Metaglip), glyburide (Diabeta, Glynase, in Glucovance), nateglinide (Starlix), pioglitazone (Actos, in Actoplus Met, in Duetact), repaglinide (Prandin), rosiglitazone (Avandia, in Avandamet, in Avandaryl), tolazamide, and tolbutamide; nefazodone; and telithromycin (Ketek). You 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, if you have or have ever had pancreatitis (swelling of the pancreas), gallstones, high levels of triglycerides (fatty substances) in your blood, diabetic ketoacidosisor kidney disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking saxagliptin, call your doctor.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking saxagliptin.
- talk to your doctor about what you should do if you get hurt or if you develop a fever or infection. These conditions may affect your blood sugar and the amount of saxagliptin you may need.
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, exercise regularly, and lose weight if necessary. This will help to control your diabetes and help saxagliptin work more effectively.
What should I do if I forget a dose?
Take 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 take a double dose to make up for a missed one unless your doctor tells you that you should.
What side effects can this medication 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.
Saxagliptin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- sore throat
- joint pain
Some side effects can be serious. If you experience any of these symptoms, stop taking saxagliptin and call your doctor immediately:
- skin peeling
- swelling of the face, lips, tongue or throat
- difficulty breathing or swallowing
- ongoing pain, that begins in the upper left or middle of the stomach but may spread to the back
- loss of appetite
Saxagliptin 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 (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).
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 emergency/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.
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor will probably order certain laboratory tests to check your body's response to saxagliptin. Your blood sugar and glycosylated hemoglobin (HbA1c) should be checked regularly to determine your response to saxagliptin. Your doctor may also tell you how to check your response to saxagliptin by measuring your blood or urine sugar levels at home. Follow these directions carefully.
You should always wear a diabetic identification bracelet to be sure you get proper treatment in an emergency.
Do not let anyone else take 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.
Brand names of combination products
- Kombiglyze® XR (containing Metformin, Saxagliptin)