Segluromet FDA Alerts

SGLT2 (sodium-glucose cotransporter-2) Inhibitors for Diabetes: Drug Safety Communication - Regarding Rare Occurrences of a Serious Infection of the Genital Area

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. 

Patients should:

• 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.

Health care 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:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm

• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[08/29/2018 - Drug Safety Communication - FDA]
 

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

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:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

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