U.S. FDA approves supplemental New Drug Applications to include landmark data in product labels for Synjardy® (empagliflozin/metformin hydrochloride), Synjardy® XR (empagliflozin/metformin hydrochloride extended-release) and Glyxambi® (empagliflozin/linagliptin) tablets

04 Jan, 2017, 17:09 ET from Eli Lilly and Company

RIDGEFIELD, Conn. and INDIANAPOLIS, Jan. 4, 2017 /PRNewswire/ -- The U.S. Food and Drug Administration (FDA) approved supplemental New Drug Applications for three type 2 diabetes medicines within the empagliflozin family to include data from the landmark EMPA-REG OUTCOME® trial. The data show that empagliflozin reduced the risk for cardiovascular death compared with placebo when added to standard of care type 2 diabetes and cardiovascular medicines in adults with type 2 diabetes and established cardiovascular disease. The data have been added to the "Clinical Studies" sections of the Prescribing Information for Synjardy® (empagliflozin/metformin hydrochloride), Synjardy® XR (empagliflozin/metformin hydrochloride extended-release) and Glyxambi® (empagliflozin/linagliptin) tablets, all of which are marketed by Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY). SYNJARDY, SYNJARDY XR and GLYXAMBI are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Empagliflozin, a component of these medicines, is indicated to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease. However, the effectiveness of SYNJARDY, SYNJARDY XR and GLYXAMBI on reducing the risk of cardiovascular death in adults with type 2 diabetes and cardiovascular disease has not been established.

"The addition of these data to the SYNJARDY, SYNJARDY XR and GLYXAMBI labels will help physicians better understand the available clinical trial evidence to help their patients who have type 2 diabetes and cardiovascular disease," said Thomas Seck, M.D., vice president, Clinical Development and Medical Affairs, Primary Care, Boehringer Ingelheim Pharmaceuticals, Inc. "As part of our long-standing and continuing efforts to help adults with type 2 diabetes, we are pleased that our discussions with the FDA have resulted in these important label updates."

In EMPA-REG OUTCOME, empagliflozin significantly reduced the relative risk of the combined primary endpoint of cardiovascular death, non-fatal heart attack or non-fatal stroke by 14 percent versus placebo (HR 0.86, 95% CI: 0.74-0.99) in adults with type 2 diabetes and established cardiovascular disease; absolute risk reduction was 1.6 percent for empagliflozin versus placebo. This primary finding was driven by a significant 38 percent reduction in the relative risk of cardiovascular death (HR 0.62, 95% CI: 0.49-0.77); absolute risk reduction was 2.2 percent for patients taking empagliflozin versus placebo. There was no change in the risk of non-fatal heart attack (HR 0.87, 95% CI: 0.70-1.09) or non-fatal stroke (HR 1.24, 95% CI: 0.92-1.67). The cardiovascular benefits of empagliflozin were consistent among patient subgroups.

SYNJARDY, SYNJARDY XR and GLYXAMBI are not for the treatment of type 1 diabetes or diabetic ketoacidosis. GLYXAMBI has not been studied in patients with a history of pancreatitis, and it is unknown if using GLYXAMBI increases the risk of developing pancreatitis in these patients.

SYNJARDY and SYNJARDY XR can cause serious side effects, including lactic acidosis (a buildup of lactic acid in the blood). Metformin, one of the medicines in SYNJARDY and SYNJARDY XR, can cause lactic acidosis, a rare, but serious condition that can cause death. Lactic acidosis is a medical emergency and must be treated in a hospital. SYNJARDY XR can cause dehydration, low blood pressure and increased ketones in the blood (ketoacidosis).

Adults with type 2 diabetes should not take SYNJARDY, SYNJARDY XR or GLYXAMBI if they have severe kidney problems or are on dialysis, or if they are allergic to empagliflozin. GLYXAMBI should not be taken by patients with a history of hypersensitivity reaction to linagliptin, such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity. There have been reports of acute pancreatitis, including fatal pancreatitis, in patients taking linagliptin, a component of GLYXAMBI. Other serious side effects associated with empagliflozin use are dehydration, low blood pressure, increased ketones in the blood (ketoacidosis), serious urinary tract infection, acute kidney injury and impairment in renal function, low blood glucose when used with insulin or insulin secretagogues (e.g., sulfonylurea, a medication used to treat type 2 diabetes), vaginal yeast infections and yeast infections of the penis, and increased cholesterol.

About Diabetes

Approximately 29 million Americans and an estimated 415 million people worldwide have diabetes, and nearly 28 percent of Americans with diabetes—totaling 8 million people—are undiagnosed. In the U.S., approximately 12 percent of those aged 20 and older have diabetes. Type 2 diabetes is the most common type, accounting for an estimated 90 to 95 percent of all diagnosed adult diabetes cases in the U.S. Diabetes is a chronic condition that occurs when the body does not properly produce or use the hormone insulin.

What are SYNJARDY and SYNJARDY XR? (www.synjardy.com)

SYNJARDY and SYNJARDY XR are prescription medicines that contain 2 diabetes medicines, empagliflozin (JARDIANCE) and metformin. SYNJARDY and SYNJARDY XR can be used along with diet and exercise to improve blood sugar in adults with type 2 diabetes, and can be used in adults with type 2 diabetes who have known cardiovascular disease when both empagliflozin and metformin are appropriate and empagliflozin is needed to reduce the risk of cardiovascular death.

SYNJARDY and SYNJARDY XR are not for people with type 1 diabetes, or for people with diabetic ketoacidosis (increased ketones in the blood or urine).

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about SYNJARDY or SYNJARDY XR?

SYNJARDY or SYNJARDY XR can cause serious side effects, including Lactic Acidosis (a build-up of lactic acid in the blood). Metformin, one of the medicines in SYNJARDY and SYNJARDY XR, can cause lactic acidosis, a rare but serious condition that can cause death. Lactic acidosis is a medical emergency and must be treated in a hospital.

Call your doctor right away if you get any of the following symptoms of lactic acidosis: cold in your hands or feet; feel dizzy or lightheaded; slow or irregular heartbeat; feel very weak or tired; have unusual muscle pain; have trouble breathing; feel sleepy or drowsy; have stomach pains, nausea, or vomiting.

You have a higher chance of getting lactic acidosis with SYNJARDY or SYNJARDY XR if you: have moderate to 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 the short term ("binge" drinking); get dehydrated (lose a large amount of body fluids); have surgery; have a heart attack, severe infection, or stroke.

Who should not take SYNJARDY or SYNJARDY XR? Do not take SYNJARDY or SYNJARDY XR if you:

  • have moderate to severe kidney problems or are on dialysis
  • have a condition called metabolic acidosis or diabetic ketoacidosis (increased ketones in the blood or urine)
  • are allergic to empagliflozin (JARDIANCE), metformin, or any of the ingredients in SYNJARDY or SYNJARDY XR. Symptoms of serious allergic reactions to SYNJARDY or SYNJARDY XR may include skin rash, raised red patches on your skin (hives), swelling of the face, lips, tongue, and throat that may cause difficulty breathing or swallowing. If you have any of these symptoms, stop taking SYNJARDY or SYNJARDY XR and contact your doctor or go to the nearest emergency room right away

What should I tell my doctor before using SYNJARDY or SYNJARDY XR?

Tell your doctor about all of your medical conditions, including if you:

  • have moderate to severe kidney problems. Your doctor may do blood tests to check your kidneys before and during treatment with SYNJARDY or SYNJARDY XR
  • have liver problems
  • have a history of urinary tract infection or problems with urination
  • have heart problems, including congestive heart failure
  • are going to have surgery
  • are eating less due to illness, surgery, or a change in your diet
  • have or have had problems with your pancreas, including pancreatitis or surgery on your pancreas
  • drink alcohol very often, or drink a lot of alcohol in the short term ("binge" drinking)
  • are going to get an injection of dye or contrast agents for an x-ray procedure. SYNJARDY or SYNJARDY XR may need to be stopped for a short time. Talk to your doctor about when you should stop SYNJARDY or SYNJARDY XR and when you should start SYNJARDY or SYNJARDY XR again
  • have type 1 diabetes. SYNJARDY or SYNJARDY XR should not be used in people with type 1 diabetes
  • are pregnant or planning to become pregnant. SYNJARDY or SYNJARDY XR may harm your unborn baby. Tell your doctor right away if you become pregnant while taking SYNJARDY or SYNJARDY XR
  • are a premenopausal woman (before the "change of life"), who does not have periods regularly or at all. Talk to your doctor about birth control choices while taking SYNJARDY or SYNJARDY XR as it may increase your chances of becoming pregnant
  • are breastfeeding or plan to breastfeed. SYNJARDY or SYNJARDY XR may pass into your breast milk and may harm your baby. Do not breastfeed while taking SYNJARDY or SYNJARDY XR.

Tell your doctor about all the medicines you take including prescription or over-the-counter medicines, vitamins, or herbal supplements.

What are the possible side effects of SYNJARDY or SYNJARDY XR?

SYNJARDY or SYNJARDY XR may cause serious side effects including:

Dehydration. SYNJARDY or SYNJARDY XR can cause some people to have dehydration (the loss of body water and salt). Dehydration may cause you to feel dizzy, faint, light-headed, or weak, especially when you stand up. You may be at higher risk of dehydration if you have low blood pressure, kidney problems, are 65 years of age or older, are on a low salt diet, or take medicines to lower your blood pressure, including water pills (diuretics).

Ketoacidosis (increased ketones in your blood or urine). Ketoacidosis is a serious condition, which may need to be treated in the hospital. Ketoacidosis may lead to death. Ketoacidosis occurs in people with type 1 diabetes and can also occur in people with type 2 diabetes taking SYNJARDY or SYNJARDY XR, even if blood sugar is less than 250 mg/dL. Stop taking SYNJARDY or SYNJARDY XR and call your doctor right away if you get any of the following symptoms, and, if possible, check for ketones in your urine:

  • nausea
  • vomiting
  • stomach-area (abdominal) pain
  • tiredness
  • trouble breathing

Kidney problems. Sudden kidney injury has happened to people taking SYNJARDY or SYNJARDY XR. Talk to your doctor right away if you reduce the amount you eat or drink, or if you lose liquids; for example, from vomiting, diarrhea, or being in the sun too long.

Serious urinary tract infections. Serious urinary tract infections can occur in people taking SYNJARDY or SYNJARDY XR and may lead to hospitalization. Tell your doctor if you have symptoms of a urinary tract infection, such as a burning feeling when passing urine, a need to urinate often or right away, pain in the lower part of your stomach or 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 SYNJARDY or SYNJARDY XR with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea medicine or insulin may need to be lowered. Symptoms of low blood sugar may include headache, drowsiness, weakness, irritability, hunger, fast heartbeat, confusion, shaking or feeling jittery, dizziness, or sweating.

Vaginal yeast infection. Women who take SYNJARDY or SYNJARDY XR may get vaginal yeast infections. Talk to your doctor if you experience vaginal odor, white or yellowish vaginal discharge (discharge may be lumpy or look like cottage cheese), and/or vaginal itching.

Yeast infection of the penis. Men who take SYNJARDY or SYNJARDY XR may get a yeast infection of the skin around the penis, especially uncircumcised males and those with chronic infections. Talk to your doctor if you experience redness, itching or swelling of the penis, rash of the penis, foul smelling discharge from the penis, and/or pain in the skin around penis.

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 blood levels before. Your doctor may do blood tests to check your vitamin B12 levels.

Increased fats in your blood (cholesterol).

The most common side effects of SYNJARDY or SYNJARDY XR include urinary tract infections, female genital infections, diarrhea, nausea, vomiting, gas, stomach pain, indigestion, weakness, headache, and stuffy or runny nose and sore throat.

These are not all the possible side effects of SYNJARDY or SYNJARDY XR. For more information, ask your doctor or pharmacist.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For more information, please see SYNJARDY Prescribing Information, SYNJARDY XR Prescribing Information, SYNJARDY Medication Guide and SYNJARDY XR Medication Guide.

SY-SYXR CONS ISI 1.3.17

What is GLYXAMBI? (www.glyxambi.com) GLYXAMBI is a prescription medication containing two medicines, empagliflozin (JARDIANCE) and linagliptin (TRADJENTA). GLYXAMBI can be used along with diet and exercise to improve blood sugar in adults with type 2 diabetes, and can be used in adults with type 2 diabetes who have known cardiovascular disease when both empagliflozin and linagliptin are appropriate and empagliflozin is needed to reduce the risk of cardiovascular death.

GLYXAMBI is not for people with type 1 diabetes or for diabetic ketoacidosis (increased ketones in the blood or urine). If you have had pancreatitis (inflammation of the pancreas) it is not known if you have a higher chance of getting pancreatitis while taking GLYXAMBI.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about GLYXAMBI?

Serious side effects can happen to people taking GLYXAMBI, including:

  • Inflammation of the pancreas (pancreatitis), which may be severe and lead to death. Before you start taking GLYXAMBI, tell your doctor if you have ever had pancreatitis, gallstones, a history of alcoholism, or high triglyceride levels. Stop taking GLYXAMBI and call your doctor 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 to your back. The pain may happen with or without vomiting. These may be symptoms of pancreatitis.
  • Dehydration. GLYXAMBI can cause some people to have dehydration (the loss of body water and salt). Dehydration may cause you to feel dizzy, faint, light -headed, or weak, especially when you stand up. You may be at higher risk of dehydration if you have low blood pressure, take medicines to lower your blood pressure, including water pills (diuretics), are on a low salt diet, have kidney problems, or are 65 years of age or older.
  • Ketoacidosis (increased ketones in your blood or urine). Ketoacidosis is a serious condition, which may need to be treated in the hospital. Ketoacidosis may lead to death. Ketoacidosis occurs in people with type 1 diabetes and can also occur in people with type 2 diabetes taking GLYXAMBI, even if blood sugar is less than 250 mg/dL. Stop taking GLYXAMBI and call your doctor right away if you get any of the following symptoms and, if possible, check for ketones in your urine:
    • nausea
    • vomiting
    • stomach-area (abdominal) pain
    • tiredness
    • trouble breathing
  • Serious urinary tract infections. Serious urinary tract infections can occur in people taking GLYXAMBI and may lead to hospitalization. Tell your doctor if you have symptoms of a urinary tract infection such as a burning feeling when passing urine, a need to urinate often or right away, pain in the lower part of your stomach or pelvis, or blood in the urine. Sometimes people also may have a fever, back pain, nausea, or vomiting.
  • Vaginal yeast infection. Women who take GLYXAMBI may get vaginal yeast infections. Talk to your doctor if you experience vaginal odor, white or yellowish vaginal discharge (discharge may be lumpy or look like cottage cheese), and/or vaginal itching.
  • Yeast infection of the penis. Men who take GLYXAMBI may get a yeast infection of the skin around the penis, especially uncircumcised males and those with chronic infections. Talk to your doctor if you experience redness, itching or swelling of the penis, rash of the penis, foul smelling discharge from the penis, and/or pain in the skin around penis.

Who should not take GLYXAMBI?

Do not take GLYXAMBI if you have severe kidney problems or are on dialysis.

Do not take GLYXAMBI if you are allergic to linagliptin (TRADJENTA), empagliflozin (JARDIANCE), or any of the ingredients in GLYXAMBI.

Symptoms of a serious allergic reaction to GLYXAMBI may include skin rash, itching, flaking or peeling; raised red patches on your skin (hives); difficulty swallowing or breathing; or swelling of your face, lips, tongue, and throat that may cause difficulty breathing or swallowing. If you have any of these symptoms, stop taking GLYXAMBI and call your doctor or go to the emergency room right away.

What should I tell my doctor before using GLYXAMBI?

Tell your doctor if you:

  • have kidney problems. Your doctor may do blood tests to check your kidneys before and during your treatment with GLYXAMBI
  • have liver problems
  • have a history of infection of the vagina or penis
  • have a history of urinary tract infections or problems with urination
  • are going to have surgery
  • are eating less due to illness, surgery, or a change in your diet
  • have or have had problems with your pancreas, including pancreatitis or surgery on your pancreas
  • drink alcohol very often, or drink a lot of alcohol in the short term ("binge" drinking)
  • have any other medical conditions
  • are pregnant or plan to become pregnant. GLYXAMBI may harm your unborn baby. Tell your doctor right away if you become pregnant during treatment with GLYXAMBI
  • are breastfeeding, or planning to breastfeed. GLYXAMBI may pass into your breast milk and may harm your baby. Do not breastfeed while taking GLYXAMBI

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. GLYXAMBI may affect the way other medicines work, and other medicines may affect how GLYXAMBI works.

Especially tell your doctor if you take:

  • insulin or other medicines that can lower your blood sugar
  • diuretics (water pills)
  • rifampin (Rifadin®, Rimactane®, Rifater®, Rifamate®)*, an antibiotic that is used to treat tuberculosis

*These trademarks are owned by third parties not affiliated with GLYXAMBI.

What are the possible side effects of GLYXAMBI?

GLYXAMBI may cause serious side effects, including:

  • Low blood sugar (hypoglycemia), if you take GLYXAMBI with another medicine that can cause low blood sugar such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea or insulin may need to be lowered. Signs and symptoms of low blood sugar may include headache, drowsiness, weakness, confusion, irritability, hunger, fast heartbeat, sweating, dizziness, or shaking or feeling jittery.
  • Allergic (hypersensitivity) reactions can happen after your first dose or up to 3 months after starting GLYXAMBI. Symptoms may include swelling of your face, lips, throat, and other areas on your skin; difficulty with swallowing or breathing; raised, red areas on your skin (hives); and/or skin rash, itching, flaking, or peeling. If you have any of these symptoms, stop taking GLYXAMBI and call your doctor or go to the emergency room right away.
  • Kidney problems. Sudden kidney injury has happened to people taking GLYXAMBI. Talk to your doctor right away if you reduce the amount you eat or drink, or if you lose liquids; for example, from vomiting, diarrhea, or being in the sun too long.
  • Increased fats in your blood (cholesterol)
  • Joint pain. Some people who take medicines called DPP-4 inhibitors, one of the medicines in GLYXAMBI, may develop joint pain that can be severe. Call your doctor if you have severe joint pain.
  • Skin reaction called bullous pemphigoid can be serious and may need to be treated in a hospital. Tell your doctor right away if you develop blisters.

The most common side effects of GLYXAMBI include urinary tract infections, stuffy or runny nose and sore throat, and upper respiratory tract infections.

These are not all the possible side effects of GLYXAMBI. For more information, ask your doctor or pharmacist.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For more information, please see Prescribing Information and Medication Guide.

GLX CONS ISI 1.3.17

Boehringer Ingelheim and Eli Lilly and Company In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in diabetes that centers on compounds representing several of the largest diabetes treatment classes. This alliance leverages the strengths of two of the world's leading pharmaceutical companies. By joining forces, the companies demonstrate commitment in the care of patients with diabetes and stand together to focus on patient needs. Find out more about the alliance at www.boehringer-ingelheim.com or www.lilly.com.

About Boehringer Ingelheim Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation.

Boehringer Ingelheim is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, the company operates globally with 145 affiliates and more than 47,000 employees. Since its founding in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel treatments for human and veterinary medicine.

Boehringer Ingelheim is committed to improving lives and providing valuable services and support to patients and families. Our employees create and engage in programs that strengthen our communities. To learn more about how we make more health for more people, visit our Corporate Social Responsibility Report.

In 2015, Boehringer Ingelheim achieved net sales of about $15.8 billion (14.8 billion euros). R&D expenditure corresponds to 20.3 percent of its net sales.

For more information please visit www.boehringer-ingelheim.us/, or follow us on Twitter @BoehringerUS.

About Lilly Diabetes Lilly has been a global leader in diabetes care since 1923, when we introduced the world's first commercial insulin. Today we are building upon this heritage by working to meet the diverse needs of people with diabetes and those who care for them. Through research and collaboration, a wide range of therapies and a continued determination to provide real solutions—from medicines to support programs and more—we strive to make life better for all those affected by diabetes around the world. For more information, visit www.lillydiabetes.com.

About Eli Lilly and Company Lilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at www.lilly.com and www.lilly.com/newsroom/social-channels.

This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about SYNJARDY, SYNJARDY XR and GLYXAMBI as treatments for adults with type 2 diabetes, and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date, that SYNJARDY, SYNJARDY XR and GLYXAMBI will receive additional regulatory approvals or that they will be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

Synjardy®, Synjardy® XR, Glyxambi® and EMPA-REG OUTCOME® are registered trademarks of Boehringer Ingelheim.

P-LLY PC-01405

CONTACT:

Jennifer Forsyth Director, Public Relations Boehringer Ingelheim Pharmaceuticals, Inc. Email: jennifer.forsyth@boehringer-ingelheim.com   Phone: (203) 791-5889

Molly McCully Communications Manager Lilly Diabetes Email: mccully_molly@lilly.com Phone: (317) 478-5423

SOURCE Eli Lilly and Company



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