AUDIENCE: Patient, Endocrinology, Health Professional, Pharmacy
ISSUE: FDA is warning that cases of a rare but serious infection of the genitals and area around the genitals have been reported with the class of type 2 diabetes medicines called sodium-glucose cotransporter-2 (SGLT2) inhibitors. This serious rare infection, called necrotizing fasciitis of the perineum, is also referred to as Fournier's gangrene. We are requiring a new warning about this risk to be added to the prescribing information of all SGLT2 inhibitors and to the patient Medication Guide.
BACKGROUND: SGLT2 inhibitors are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. SGLT2 inhibitors lower blood sugar by causing the kidneys to remove sugar from the body through the urine. First approved in 2013, medicines in the SGLT2 inhibitor class include canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin (see FDA-Approved SGLT2 Inhibitors). In addition, empagliflozin is approved to lower the risk of death from heart attack and stroke in adults with type 2 diabetes and heart disease. Untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease.
RECOMMENDATION: To read all of the recommendations see the Drug Safety Communication, available at: http://bit.ly/2wNOpdK.
- Seek medical attention immediately if you experience any symptoms of tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4 F or a general feeling of being unwell. These symptoms can worsen quickly, so it is important to seek treatment right away.
- Read the patient Medication Guide every time you receive a prescription for an SGLT2 inhibitor because there may be new or important additional information about your drug. The Medication Guide explains the benefits and risks associated with the medicine
Health care professionals should:
- Assess patients for Fournier's gangrene if they present with the symptoms described above. If suspected, start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary.
- Discontinue the SGLT2 inhibitor, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.
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?
Dapagliflozin is used along with diet and exercise, and sometimes with other medications, 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). Dapagliflozin is in a class of medications called sodium-glucose co-transporter 2 (SGLT2) inhibitors. It lowers blood sugar by causing the kidneys to get rid of more glucose in the urine. Dapagliflozin 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 dapagliflozin, 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?
Dapagliflozin comes as a tablet to take by mouth. It is taken usually with or without food once a day in the morning. Take dapagliflozin 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 dapagliflozin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Your doctor may start you on a low dose of dapagliflozin and increase your dose if needed.
Dapagliflozin controls type 2 diabetes but does not cure it. Continue to take dapagliflozin even if you feel well. Do not stop taking dapagliflozin without talking to your doctor.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with dapagliflozin 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.
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 dapagliflozin,
- tell your doctor and pharmacist if you are allergic to dapagliflozin, any other medications, or any of the ingredients in dapagliflozin 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: angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), captopril, enalapril (Vasotec, in Vaseretic), fosinopril, lisinopril (in Zestoretic), moexipril (Univasc, in Uniretic), perindopril (Aceon, in Prestalia), ramipril (Altace), and trandolapril (Mavik, in Tarka); angiotensin receptor blockers (ARB) such as azilsartan (Edarbi, in Edarbyclor), candesartan (Atacand, in Atacand HCT), eprosartan (Teveten), irbesartan (Avapro, in Avalide), losartan (Cozaar, in Hyzaar), olmesartan (Benicar, in Azor, in Benicar HCT, in Tribenzor), telmisartan (Micardis, in Micardis HCT, in Twynsta); aspirin and other nonsteroidal anti-inflammatory medications (NSAIDS) such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn); diabetes medications such as glimepiride (Amaryl, in Duetact), glipizide (Glucotrol), glyburide (DiaBeta, Glynase), repaglinide (Prandin, in Prandimet), and tolbutamide; diuretics ('water pills'); and insulin.
- tell your doctor if you are on dialysis and if you have or have ever had kidney disease. Your doctor may tell you not to take dapagliflozin.
- tell your doctor if you regularly drink alcohol or sometimes drink large amounts of alcohol in a short time (binge drinking) or if you are on a low sodium diet. Also tell your doctor if you have or have ever had heart failure, pancreatic disease including pancreatitis (swelling of the pancreas) or have had surgery on your pancreas, urinary tract infections or problems urinating, low blood pressure, bladder cancer, yeast infections in the genital area, or liver disease. If you are male, tell your doctor if you have never been circumcised. Also tell your doctor, if you eating less due to illness, surgery or a change in your diet, or have recently had diarrhea, vomiting, not been drinking enough fluids, been in the sun too long, or have been sweating a lot, which may cause dehydration (loss of a large amount of body fluids).
- tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking dapagliflozin, call your doctor.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking dapagliflozin.
- alcohol may cause a change in blood sugar. Ask your doctor about the safe use of alcoholic beverages while you are taking dapagliflozin.
- you should know that dapagliflozin may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. If you have this problem, call your doctor. This problem is more common when you first start taking dapagliflozin. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
- 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 dapagliflozin 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 healthful diet and exercise regularly.
Follow your doctor's instructions about drinking enough fluids throughout the day while you are on this medication.
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.
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.
Dapagliflozin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- urinating a lot, including at night
- increased thirst
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:
- frequent, urgent, burning, or painful urination
- urine that is cloudy, red, pink, or brown
- strong smelling urine
- decrease in amount of urine
- pelvic or rectal pain
- (in women) vaginal odor, white or yellowish vaginal discharge (may be lumpy or look like cottage cheese), or vaginal itching
- (in men) redness, itching, or swelling of the penis; rash on the penis; foul smelling discharge from the penis; or pain in the skin around the penis
- swelling of the legs or feet
If you experience any of the following symptoms, stop taking dapagliflozin and call your doctor immediately or get emergency medical treatment:
- difficulty breathing or swallowing
- swelling of the face, throat, tongue, lips, mouth, or eyes
If you experience any of the following symptoms of ketoacidosis, stop taking dapagliflozin and call your doctor immediately or get emergency medical treatment. If possible, check for ketones in your urine if you have these symptoms, even if your blood sugar is less than 250 mg/dL:
- stomach-area pain
- difficulty breathing
Dapagliflozin 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.
It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org
In case of emergency/overdose
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call 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 before and during your treatment to check your body's response to dapagliflozin.
Your blood sugar levels should be checked regularly to determine your response to dapagliflozin. Your doctor will order other lab tests, including glycosylated hemoglobin (HbA1c), to check your response to dapagliflozin. Your doctor will also tell you how to check your response to this medication by measuring your blood sugar levels at home. Follow these instructions carefully.
Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking dapagliflozin. Because of the way this medication works, your urine may test positive for glucose.
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.
- Qtern® (as a combination product containing Dapagliflozin, Saxagliptin)
Brand names of combination products
- Xigduo® XR (containing Dapagliflozin, Metformin)