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Kombiglyze XR FDA Alerts

The FDA Alert(s) below may be specifically about Kombiglyze XR or relate to a group or class of drugs which include Kombiglyze XR (metformin/saxagliptin).

MedWatch Safety Alerts are distributed by the FDA and published by Drugs.com. Following is a list of possible medication recalls, market withdrawals, alerts and warnings. For the latest FDA MedWatch alerts, go here.

Recent FDA Alert(s) for metformin/saxagliptin

Metformin-containing Drugs: Drug Safety Communication - Revised Warnings for Certain Patients With Reduced Kidney Function

Apr 8, 2016

Audience: Pharmacy, Nephrology, Internal Medicine, Patient

ISSUE: FDA is requiring labeling changes regarding the recommendations for metformin-containing medicines for diabetes to expand metformin’s use in certain patients with reduced kidney function. The current labeling strongly recommends against use of metformin in some patients whose kidneys do not work normally. FDA was asked to review numerous medical studies regarding the safety of metformin use in patients with mild to moderate impairment in kidney function, and to change the measure of kidney function in the metformin drug labeling that is used to determine whether a patient can receive metformin.

FDA concluded, from the review of studies published in the medical literature, that metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function. FDA is requiring changes to the metformin labeling to reflect this new information and provide specific recommendations on the drug’s use in patients with mild to moderate kidney impairment.

FDA is also requiring manufacturers to revise the labeling to recommend that the measure of kidney function used to determine whether a patient can receive metformin be changed from one based on a single laboratory parameter (blood creatinine concentration) to one that provides a better estimate of renal function (i.e., glomerular filtration rate estimating equation (eGFR)). This is because in addition to blood creatinine concentration, the glomerular filtration rate takes into account additional parameters that are important, such as the patient’s age, gender, race and/or weight. See the FDA Drug Safety Communication for additional information, including a data summary and a list of metformin-containing drugs.

BACKGROUND: Metformin-containing medicines are available by prescription only and are used along with diet and exercise to lower blood sugar levels in patients with type 2 diabetes. When untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease. Metformin-containing medicines are available as single-ingredient products and also in combination with other drugs used to treat diabetes. The current drug labeling strongly recommends against metformin use in some patients whose kidneys do not work normally because use of metformin in these patients can increase the risk of developing a serious and potentially deadly condition called lactic acidosis, in which too much lactic acid builds up in the blood.

RECOMMENDATION: Healthcare professionals should follow the latest recommendations when prescribing metformin-containing medicines to patients with impaired kidney function. Patients should talk to their health care professionals if they have any questions or concerns about taking metformin.

The labeling recommendations on how and when kidney function is measured in patients receiving metformin will include the following information: 

  • Before starting metformin, obtain the patient’s eGFR.
  • Metformin is contraindicated in patients with an eGFR below 30 mL/minute/1.73 m2.
  • Starting metformin in patients with an eGFR between 30-45 mL/minute/1.73 m2 is not recommended.
  • Obtain an eGFR at least annually in all patients taking metformin. In patients at increased risk for the development of renal impairment such as the elderly, renal function should be assessed more frequently.
  • In patients taking metformin whose eGFR later falls below 45 mL/minute/1.73 m2, assess the benefits and risks of continuing treatment.  Discontinue metformin if the patient’s eGFR later falls below 30 mL/minute/1.73 m2.
  • Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/minute/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast.  Re-evaluate eGFR 48 hours after the imaging procedure; restart metformin if renal function is stable. 

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

[04/08/2016 - Drug Safety Communication - FDA]
 

Diabetes Medications Containing Saxagliptin and Alogliptin: Drug Safety Communication - Risk of Heart Failure

Apr 5, 2016

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.

Medicines containing saxagliptin and alogliptin include:

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.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

[04/05/2016 - Drug Safety Communication - FDA]

DPP-4 Inhibitors for Type 2 Diabetes: Drug Safety Communication - May Cause Severe Joint Pain

Aug 28, 2015

Audience: Patient, Endocrinology, Family Practice, Internal Medicine

ISSUE: The U.S. Food and Drug Administration (FDA) is warning that the type 2 diabetes medicines sitagliptin, saxagliptin, linagliptin, and alogliptin may cause joint pain that can be severe and disabling. FDA has added a new Warning and Precaution about this risk to the labels of all medicines in this drug class, called dipeptidyl peptidase-4 (DPP-4) inhibitors. See the Drug Safety Communication for a complete list of all FDA-approved DPP-4 inhibitors.

BACKGROUND: DPP-4 inhibitors are used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. When untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease. These medicines are available as single-ingredient products and in combination with other diabetes medicines such as metformin.

RECOMMENDATION: Patients should not stop taking their DPP-4 inhibitor medicine, but should contact their health care professional right away if they experience severe and persistent joint pain. Health care professionals should consider DPP-4 inhibitors as a possible cause of severe joint pain and discontinue the drug if appropriate. 

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

[08/28/2015 - Drug Safety Communication - FDA]

Saxagliptin (marketed as Onglyza and Kombiglyze XR): Drug Safety Communication - FDA to Review Heart Failure Risk

Feb 11, 2014

Audience: Cardiology, Endocrinology, Pharmacy

ISSUE: 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. FDAs 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. 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 FDA will conduct a thorough analysis and report findings publicly.

At this time, FDA considers information from the NEJM study to be preliminary. Analysis of the saxagliptin clinical trial data is part of a broader evaluation of all type 2 diabetes drug therapies and cardiovascular risk.

BACKGROUND: 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.

RECOMMENDATION: 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.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

 

[02/11/2014 - Drug Safety Communication - FDA]

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