Qternmet XR

Qternmet XR is a prescription medication used to improve blood glucose control in adults with type 2 diabetes. 

Qternmet XR is a single product that contains that contains dapagliflozin, saxagliptin, and metformin hydrochloride. Dapagliflozin belongs to a group of drugs called sodium-glucose co-transporter 2 (SGLT2) inhibitors. These work by helping the kidneys get glucose out of the body in the urine. Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor which helps lower blood sugar levels. Metformin belongs to a group of drugs called biguanides. These work by decreasing the amount of glucose your body can absorb from food and decreasing the amount of glucose made by the liver. 

Qternmet XR comes in tablet form. It is taken once daily with food. Swallow Qternmet XR whole. Do not cut, crush or chew Qternmet XR tablets.

Common side effects include upper respiratory tract infection, urinary tract infection, and abnormal amounts of fats in the blood.

Qternmet XR is a prescription medicine that contains dapagliflozin, saxagliptin, and metformin hydrochloride. Qternmet XR is used along with diet and exercise to improve blood sugar (glucose) control in adults with type 2 diabetes.

• Qternmet XR is not for people with type 1 diabetes.
• Qternmet XR is not for people with diabetic ketoacidosis (increased ketones in your blood or urine). 
• Qternmet XR is only for people currently taking metformin.
• It is not known if Qternmet XR is safe and effective in children younger than 18 years of age.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Qternmet XR. See the “Qternmet XR Precautions” section.

The most common side effects of Qternmet XR include:

• upper respiratory tract infection 
• abnormal amounts of fats in the blood (dyslipidemia)
• urinary tract infection

These are not all of the possible side effects of Qternmet XR.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. 

• Know the medicines you take.
• Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

Qternmet XR may affect the way other medicines work, and other medicines may affect how Qternmet XR works. Contact your healthcare provider if you will be starting or stopping certain other types of medicines, such as antibiotics, or medicines that treat fungus or HIV/AIDS, because your dose of Qternmet XR might need to be changed.

Serious side effects can happen to people taking Qternmet XR including:

• Lactic Acidosis. Metformin, one of the medicines in Qternmet XR can cause a rare but serious condition called lactic acidosis (a build-up of an acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in the hospital. Call your healthcare provider right away if you have any of the following symptoms, which could be signs of lactic acidosis:
  • you feel cold in your hands or feet
  • you feel dizzy or lightheaded
  • you have a slow or irregular heartbeat
  • you feel very weak or tired
  • you have unusual (not normal) muscle pain
  • you have trouble breathing
  • you feel unusual sleepiness or sleep longer than usual
  • you have stomach pains, nausea, or vomiting

Most people who have had lactic acidosis with metformin have other things that, combined with the metformin use, led to the lactic acidosis. Tell your healthcare provider if you have any of the following, because you have a higher chance for getting lactic acidosis with Qternmet XR if you:

• have severe kidney problems or your kidneys are affected by certain x-ray tests that use injectable dye
• have liver problems
• drink alcohol very often, or drink a lot of alcohol in short-term "binge" drinking
• get dehydrated (lose a large amount of body fluids). This can happen if you are sick with a fever, vomiting, or diarrhea. Dehydration can also happen when you sweat a lot with activity or exercise and do not drink enough fluids.
• have surgery
• have a heart attack, severe infection, or stroke.

The best way to keep from having a problem with lactic acidosis from metformin is to tell your healthcare provider if you have any of the problems in the list above. Your healthcare provider may decide to stop your Qternmet XR for a while if you have any of these problems.

• Inflammation of the pancreas (pancreatitis). Saxagliptin, one of the medicines in Qternmet XR can cause inflammation of the pancreas, which may be severe and lead to death. Certain medical problems make you more likely to get pancreatitis. Before you start taking Qternmet XR tell your healthcare provider if you have ever had:
  • inflammation of your pancreas (pancreatitis)
  • stones in your gallbladder (gallstones)
  • a history of alcoholism
  • high blood triglyceride levels

It is not known if having these medical problems will make you more likely to get pancreatitis with Qternmet XR. Stop taking Qternmet XR and contact your healthcare provider right away if you have pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen through to your back. The pain may happen with or without vomiting. These may be symptoms of pancreatitis.

• Heart failure. Heart failure means your heart does not pump blood well enough. Before you start taking Qternmet XR tell your healthcare provider if you have ever had heart failure or have problems with your kidneys. Contact your healthcare provider right away if you have any of the following symptoms of heart failure:
  • increasing shortness of breath or trouble breathing, especially when you lie down
  • swelling or fluid retention, especially in the feet, ankles, or legs
  • an unusually fast increase in weight
  • unusual tiredness
• Dehydration. Qternmet XR can cause some people to become dehydrated (the loss of body water and salt). Dehydration may cause you to feel dizzy, faint, lightheaded, or weak, especially when you stand up (orthostatic hypotension). You may be at a higher risk of dehydration if you:
  • have low blood pressure
  • take medicines to lower your blood pressure, including water pills (diuretics) o are 65 years of age or older
  • are on a low salt diet
  • have kidney problems

• Ketoacidosis (increased ketones in your blood or urine). Ketoacidosis has happened in people who have type 1 diabetes or type 2 diabetes, during treatment with dapagliflozin, one of the medicines in Qternmet XR. Ketoacidosis is a serious condition, which may need to be treated in a hospital. Ketoacidosis may lead to death. Ketoacidosis can happen with dapagliflozin even if your blood sugar is less than 250 mg/dL. Stop taking Qternmet XR and call your healthcare provider right away if you get any of the following symptoms:

  • nausea
  • tiredness
  • vomiting
  • trouble breathing
  • stomach pain

If you get any of these symptoms during treatment with Qternmet XR if possible check for ketones in your urine, even if your blood sugar is less than 250 mg/dL.

• Kidney problems. Sudden kidney injury has happened to people taking dapagliflozin. Talk to your healthcare provider right away if you:

  • reduce the amount of food or liquid you drink, for example if you are sick and cannot eat, or 
  • you start to lose liquids from your body with vomiting, diarrhea, or being in the sun too long.
• Serious urinary tract infections. Serious urinary tract infections that may lead to hospitalization have happened in people who are taking dapagliflozin. Tell your healthcare provider if you have any signs or symptoms of a urinary tract infection such as a burning feeling when passing urine, a need to urinate often, the need to urinate right away, pain in the lower part of your stomach (pelvis), or blood in the urine. Sometimes people also may have a fever, back pain, nausea or vomiting.
• Low blood sugar (hypoglycemia). If you take Qternmet XR with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin, this can increase your risk of getting low blood sugar. Tell your healthcare provider if you take other diabetes medicines. Signs and symptoms of low blood sugar may include:
  • shaking or feeling jittery 
  • hunger
  • change in mood
  • sweating 
  • headache 
  • confusion
  • rapid heartbeat
  • drowsiness
  • irritability
  • change in vision
  • weakness

• A rare but serious bacterial infection that causes damage to the tissue under the skin (necrotizing fasciitis) in the area between and around the anus and genitals (perineum). Necrotizing fasciitis of the perineum has happened in women and men who take dapagliflozin, one of the medicines in Qternmet XR. Necrotizing fasciitis of the perineum may lead to hospitalization, may require multiple surgeries and may lead to death. Seek medical attention immediately if you have fever or you are feeling very weak, tired or uncomfortable (malaise) and you develop any of the following symptoms in the area between and around the anus and genitals:

  • pain or tenderness
  • swelling
  • redness of skin

• Serious allergic reaction. Qternmet XR may cause serious allergic reactions. Stop taking QTERNMET XR and get medical help right away if you develop any of the following symptoms of a serious allergic reaction including:

  • swelling of the face, lips, tongue, throat and other areas of your skin
  • difficulty with swallowing or breathing
  • skin rash, itching, flaking, or peeling
  • raised red patches on your skin (hives)

• Low vitamin B12 (vitamin B12 deficiency). Using metformin for long periods of time may cause a decrease in the amount of vitamin B12 in your blood, especially if you have had low vitamin B12 levels before. Your healthcare provider may do blood tests to check your vitamin B12 levels.

• Vaginal yeast infection. Women who take Qternmet XR may get vaginal yeast infections. Symptoms of a vaginal yeast infection include:

  • vaginal odor 
  • white or yellowish vaginal discharge (discharge may be lumpy or look like cottage cheese)
  • vaginal itching

• Yeast infection of the penis (balanitis). Men who take Qternmet XR may get a yeast infection of the skin around the penis. Certain men who are not circumcised may have swelling of the penis that makes it difficult to pull back the skin around the tip of the penis. Other symptoms of a yeast infection of the penis include:

  • redness, itching, or swelling of the penis
  • rash of the penis
  • foul smelling discharge from the penis
  • pain in the skin around the penis

Talk to your healthcare provider about what to do if you get symptoms of a yeast infection of the vagina or penis. Your healthcare provider may suggest you use an over-the-counter antifungal medicine. Talk to your healthcare provider right away if you use an over-the-counter antifungal medicine and your symptoms do not go away.

• Increased fats in your blood (bad cholesterol or LDL).
• Bladder cancer. In studies of dapagliflozin in people with diabetes, bladder cancer occurred in a few more people who were taking dapagliflozin than in people who were taking other diabetes medicines. There were too few cases to know if bladder cancer was related to dapagliflozin. You should not take Qternmet XR if you have bladder cancer. Tell your healthcare provider right away if you have any of the following symptoms: 
  • blood or a red color in your urine
  • pain while you urinate
• Joint pain. Some people who take DPP-4 inhibitors like saxagliptin, may develop joint pain that can be severe. Call your healthcare provider right away if you have severe joint pain.
• Skin reaction. Some people who take DPP-4 inhibitors, one of the medicines in Qternmet XR may develop a skin reaction called bullous pemphigoid that can require treatment in a hospital. Tell your healthcare provider right away if you develop blisters or the breakdown of the outer layer of your skin (erosion). Your healthcare provider may tell you to stop taking Qternmet XR.

Do not take Qternmet XR if you:

• are allergic to dapagliflozin, saxagliptin, metformin, or any of the ingredients in Qternmet XR. Symptoms of a serious allergic reaction to Qternmet XR may include:

  • swelling of the face, lips, throat and other areas of your skin
  • difficulty with swallowing or breathing
  • skin rash, itching, flaking or peeling
  • raised red areas on your skin (hives)

If you have any of these symptoms, stop taking Qternmet XR and contact your healthcare provider or go to the nearest hospital emergency room right away.

• have moderate to severe kidney problems or are on dialysis.
• have a condition called metabolic acidosis or diabetic ketoacidosis (increased ketones in your blood or urine).

Avoid drinking alcohol very often or drinking a lot of alcohol in a short period of time (“binge” drinking). It can increase your chances of getting serious side effects.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Qternmet XR, there are no specific foods that you must exclude from your diet when receiving this medication.

Avoid drinking alcohol very often or drinking a lot of alcohol in a short period of time (“binge” drinking). It can increase your chances of getting serious side effects.

Before taking Qternmet XR, tell your healthcare provider about all of your medical conditions, including if you:

• have type 1 diabetes or have had diabetic ketoacidosis (increased ketones in your blood or urine).
• are going to have surgery.
• are eating less due to illness, surgery or a change in your diet.
• drink alcohol very often or drink a lot of alcohol in the short term (“binge” drinking).
• have kidney problems.
• have liver problems.
• have a history of urinary tract infections or problems urinating.
• have heart problems, including heart failure.
• have had swelling of the face, lips, tongue and throat (angioedema) when you used a medicine called a dipeptidyl peptidase-4 (DPP-4) inhibitor like saxagliptin, one of the medicines in Qternmet XR. If you are not sure if you have taken this medicine, ask your healthcare provider.
• have or have had bladder cancer.
• have or have had problems with your pancreas, including pancreatitis or surgery on your pancreas.
• are going to get injection of dye or contrast agents for an x-ray procedure. Qternmet XR may need to be stopped for a short time. Talk to your healthcare provider about when you should stop Qternmet XR and when you should start Qternmet XR again. 
• are pregnant or plan to become pregnant. Qternmet XR may harm your unborn baby. If you are pregnant or plan to become pregnant, call your healthcare provider right away to talk about the best way to control your blood sugar.
• are a woman who has not gone through menopause (premenopausal) who does not have periods regularly or at all. Qternmet XR can cause the release of an egg from an ovary in a woman (ovulation). This can increase your chance of getting pregnant.
• are breastfeeding or plan to breastfeed. It is not known if Qternmet XR passes into your breast milk. Talk with your healthcare provider about the best way to feed your baby if you are taking Qternmet XR. Breastfeeding is not recommended while taking Qternmet XR.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

In animal studies, pregnant animals were given dapagliflozin (1 of 3 medicines in Qternmet XR tablets) and had some babies born with problems. No well-controlled studies have been done in humans. 

Based on animal studies showing adverse effects from dapagliflozin, Qternmet XR is not recommended during the second and third trimesters of pregnancy.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Qternmet XR crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using this medication.

• Take Qternmet XR exactly as your healthcare provider tells you to take it.
• Do not change your dose of Qternmet XR without talking to your healthcare provider.
• Take Qternmet XR by mouth 1 time each day in the morning with food.
• Swallow Qternmet XR whole. Do not cut, crush or chew Qternmet XR tablets.
• You may sometimes pass a soft mass in your stools (bowel movement) that looks like Qternmet XR tablets.
• During periods of stress on the body, such as fever, trauma, infection or surgery, contact your healthcare provider right away as your medicine needs may change.
• Stay on your prescribed diet and exercise program while taking Qternmet XR.
• Your healthcare provider may do certain blood tests before you start Qternmet XR and during your treatment.
• Your healthcare provider should test your blood to measure how well your kidneys are working before and during your treatment with Qternmet XR.
• Your healthcare provider will check your diabetes with regular blood tests, including your blood sugar levels and your HbA1c.
• Follow your healthcare provider’s instructions for treating low blood sugar (hypoglycemia). Talk to your healthcare provider if low blood sugar is a problem for you.
• Qternmet XR will cause your urine to test positive for glucose.
• If you miss a daily dose of Qternmet XR and it is more than 12 hours until your next dose, take the missed dose as soon as possible with food.
• If you miss a daily dose of Qternmet XR and it is less than 12 hours until your next dose, skip the missed dose. Take the next dose at your regular time.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• other medical conditions you have
• other medications you are taking
• how you respond to this medication 

For patients not currently taking dapagliflozin, the recommended starting total daily dose of Qternmet XR is a 5 mg dapagliflozin/5 mg saxagliptin/1000 mg or 2000 mg metformin hydrochloride (HCl) once daily. 

• The maximum recommended daily dose is 10 mg dapagliflozin, 5 mg saxagliptin and 2000 mg metformin HCl.

If you take too much Qternmet XR, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

Store Qternmet XR at room temperature between 68°F to 77°F (20°C to 25°C).

Keep Qternmet XR and all medicines out of the reach of children.

WARNING: LACTIC ACIDOSIS

• Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin­ associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin­ associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.
• Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
• Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information.
• If metformin-associated lactic acidosis is suspected, immediately discontinue Qternmet XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.