Kombiglyze XR (Saxagliptin/metformin hydrochloride Tabs
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FDA Drug Safety Communication: FDA to review heart failure risk with diabetes drug saxagliptin (marketed as Onglyza and Kombiglyze XR)
The U.S. Food and Drug Administration (FDA) has requested clinical trial data from the manufacturer of saxagliptin to investigate a possible association between use of the type 2 diabetes drug and heart failure. Our request resulted from a study published in the New England Journal of Medicine (NEJM), which reported an increased rate of hospitalization for heart failure, when the heart does not pump blood well enough, with use of saxagliptin (marketed as Onglyza and Kombiglyze XR) compared to an inactive treatment.1 The study did not find increased rates of death or other major cardiovascular risks, including heart attack or stroke, in patients who received saxagliptin. The manufacturer is expected to submit the trial data to FDA by early March 2014, after which we will conduct a thorough analysis and report our findings publicly.At this time, we consider information from the NEJM study to be preliminary. Our analysis of the saxagliptin clinical trial data is part of a broader evaluation of all type 2 diabetes drug therapies and cardiovascular risk.2 Patients should not stop taking saxagliptin and should speak with their health care professionals about any questions or concerns. Health care professionals should continue to follow the prescribing recommendations in the drug labels.
Type 2 diabetes is a disease in which there is a high level of sugar, or glucose, in the blood because the body does not make or properly use the hormone insulin. If left untreated, type 2 diabetes can lead to serious problems. Saxagliptin is used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. It works by increasing the amount of insulin produced by the body after meals, when blood sugar is high.
Source : FDA (Feb 2014)
FDA Drug Safety Communication: FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes
[3-14-2013] The U.S. Food and Drug Administration (FDA) is evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis, or inflammation of the pancreas, and pre-cancerous cellular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.
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.
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 communicate its final conclusions and recommendations when its review is complete or when the Agency has additional information to report.
FDA previously warned the public about postmarketing reports of acute pancreatitis, including fatal and serious nonfatal cases, associated with the use of the incretin mimetic drugs exenatide and sitagliptin. A recently published study that examined insurance records also found the use of exenatide or sitagliptin could double the risk of developing acute pancreatitis.1 The Warnings and Precautions section of the drug labels and the 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. Further, 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.
FDA is continuing to evaluate all available data to further understand this potential safety issue. In addition, 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 urges both patients and health care professionals to report adverse events involving incretin mimetics to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of this page.
Reference
1. Singh S, Chang HY, Richards TM, Weiner JP, Clark JM, Segal JB. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med 2013 Feb 25:1-6. doi: 10.1001/jamainternmed.2013.2720. [Epub ahead of print].
Source : FDA (March 2013)
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Kombiglyze XR (Saxagliptin/metformin hydrochloride Tabs
CONTRAINDICATIONS
Link to Source
FDA Drug Safety Communication: FDA to review heart failure risk with diabetes drug saxagliptin (marketed as Onglyza and Kombiglyze XR)
The U.S. Food and Drug Administration (FDA) has requested clinical trial data from the manufacturer of saxagliptin to investigate a possible association between use of the type 2 diabetes drug and heart failure. Our request resulted from a study published in the New England Journal of Medicine (NEJM), which reported an increased rate of hospitalization for heart failure, when the heart does not pump blood well enough, with use of saxagliptin (marketed as Onglyza and Kombiglyze XR) compared to an inactive treatment.1 The study did not find increased rates of death or other major cardiovascular risks, including heart attack or stroke, in patients who received saxagliptin. The manufacturer is expected to submit the trial data to FDA by early March 2014, after which we will conduct a thorough analysis and report our findings publicly.At this time, we consider information from the NEJM study to be preliminary. Our analysis of the saxagliptin clinical trial data is part of a broader evaluation of all type 2 diabetes drug therapies and cardiovascular risk.2 Patients should not stop taking saxagliptin and should speak with their health care professionals about any questions or concerns. Health care professionals should continue to follow the prescribing recommendations in the drug labels.
Type 2 diabetes is a disease in which there is a high level of sugar, or glucose, in the blood because the body does not make or properly use the hormone insulin. If left untreated, type 2 diabetes can lead to serious problems. Saxagliptin is used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. It works by increasing the amount of insulin produced by the body after meals, when blood sugar is high.
Source : FDA (Feb 2014)
FDA Drug Safety Communication: FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes
[3-14-2013] The U.S. Food and Drug Administration (FDA) is evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis, or inflammation of the pancreas, 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.
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.
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 communicate its final conclusions and recommendations when its review is complete or when the Agency has additional information to report.
FDA previously warned the public about postmarketing reports of acute pancreatitis, including fatal and serious nonfatal cases, associated with the use of the incretin mimetic drugs exenatide and sitagliptin. A recently published study that examined insurance records also found the use of exenatide or sitagliptin could double the risk of developing acute pancreatitis.1 The Warnings and Precautions section of the drug labels and the 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. Further, 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.
FDA is continuing to evaluate all available data to further understand this potential safety issue. In addition, 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 urges both patients and health care professionals to report adverse events involving incretin mimetics to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of this page.
Reference
1. Singh S, Chang HY, Richards TM, Weiner JP, Clark JM, Segal JB. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med 2013 Feb 25:1-6. doi: 10.1001/jamainternmed.2013.2720. [Epub ahead of print].
Source : FDA (March 2013)
Link to Source
Kombiglyze XR (Saxagliptin/metformin hydrochloride Tabs
CONTRAINDICATIONS
- History of a serious hypersensitivity reaction to Kombiglyze XR or saxagliptin, such as anaphylaxis, angioedema, or exfoliative skin conditions.
- There have been postmarketing reports of acute pancreatitis in patients taking saxagliptin. After initiation of Kombiglyze XR , patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, Kombiglyze XR should promptly be discontinued and appropriate management should be initiated. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using Kombiglyze XR.
- There have been postmarketing reports of serious hypersensitivity reactions in patients treated with saxagliptin. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with saxagliptin, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue Kombiglyze XR , assess for other potential causes for the event, and institute alternative treatment for diabetes.
- Use caution in a patient with a history of angioedema to another dipeptidyl peptidase-4 (DPP4) inhibitor because it is unknown whether such patients will be predisposed to angioedema with Kombiglyze XR.
- Hypersensitivity-related events, such as urticaria and facial edema in the 5-study pooled analysis up to Week 24 were reported in 1.5%, 1.5%, and 0.4% of patients who received saxagliptin 2.5 mg, saxagliptin 5 mg, and placebo, respectively. None of these events in patients who received saxagliptin required hospitalization or were reported as life-threatening by the investigators. One saxagliptin-treated patient in this pooled analysis discontinued due to generalized urticaria and facial edema.
- Patients should be informed that acute pancreatitis has been reported during postmarketing use of saxagliptin. Before initiating Kombiglyze XR , patients should be questioned about other risk factors for pancreatitis, such as a history of pancreatitis, alcoholism, gallstones, or hypertriglyceridemia. Patients should also be informed that persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Patients should be instructed to promptly discontinue Kombiglyze XR and contact their physician if persistent severe abdominal pain occurs.
- Patients should be informed that serious allergic (hypersensitivity) reactions, such as angioedema, anaphylaxis, and exfoliative skin conditions, have been reported during postmarketing use of saxagliptin. If symptoms of these allergic reactions (such as rash, skin flaking or peeling, urticaria, swelling of the skin, or swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing) occur, patients must stop taking Kombiglyze XR and seek medical advice promptly.
Link to Source