Usual Adult Dose for Diabetes Type 2

Individualize initial dose based on the patient's current regimen:

• For patients on metformin, with or without linagliptin: Initiate with a similar metformin dose plus empagliflozin 10 mg and linagliptin 5 mg orally once a day
• For patients on metformin and any regimen containing empagliflozin, with or without linagliptin: Initiate with a similar dose of metformin, the same empagliflozin dose, and linagliptin 5 mg orally once a day

• Maximum doses: Empagliflozin 25 mg/day; Linagliptin 5 mg/day; Metformin 2000 mg/day

• When used in combination with insulin or an insulin secretagogue, a lower dose of insulin or insulin secretagogue should be considered to reduce the risk of hypoglycemia.
• Correct volume depletion prior to beginning therapy.
• This drug is not recommended in patients with type 1 diabetes mellitus; it may increase the risk of ketoacidosis in these patients.
• This drug has not been studied in patients with a history of pancreatitis and therefore it is unknown if patients with a history of pancreatitis are at an increased risk for developing pancreatitis while using this drug.

• As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• Empagliflozin is indicated to reduce the risk of cardiovascular (CV) death in adults with type 2 diabetes mellitus and established CV disease.

Renal Dose Adjustments

eGFR 45 mL/min/1.73 m2 or greater: No dose adjustment recommended
eGFR less than 45 mL/min/1.73 m2: Therapy should not be initiated
eGFR 30 mL/min/1.73 m2 or less: Contraindicated

IODINATED CONTRAST PROCEDURE:

• Stop this drug at time of, or prior to, an iodinated contrast imaging procedure for patients with an eGFR less than 60 mL/min/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure
• Stop this drug in patients who will be administered intra-arterial iodinated contrast
• Reevaluate eGFR 48 hours after the imaging procedure; this drug may be restarted once adequate renal function is confirmed

Liver Dose Adjustments

Avoid use in patients with clinical or laboratory evidence of hepatic disease

Dose Adjustments

Elderly: Assess renal function more frequently in geriatric patients; adjust dose based on renal function; metformin should not be initiated unless adequate CrCl (or eGFR) is confirmed

• The risk of volume depletion associated with empagliflozin use should be considered

• Cationic drugs may reduce metformin elimination; monitor and adjust dose as needed

• Consider dose adjustment of insulin or insulin secretagogue to prevent hypoglycemia

• Stop this drug at time of, or prior to, an iodinated contrast imaging procedure for patients with an eGFR less than 60 mL/min/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure
• Stop this drug in patients who will be administered intra-arterial iodinated contrast
• Reevaluate eGFR 48 hours after the imaging procedure; this drug may be restarted once adequate renal function is confirmed

Precautions

US BOXED WARNING: LACTIC ACIDOSIS:

• Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias; 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 has been characterized by elevated blood lactate levels (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally greater than 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 and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

• Severe renal impairment (eGFR less than 30 mL/min/1.73 m2), ESRD, or dialysis
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis
• Hypersensitivity to active substances or any product excipients; reactions such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity have occurred

Dialysis

Contraindicated

Other Comments

Administration advice:

• Take orally once a day with morning meal; swallow whole, do not split, crush, dissolve, or chew before swallowing
• Incompletely dissolved tablets may appear in the feces; if patient reports seeing tablets in feces, adequacy of glycemic control should be assessed

• This drug should not be used in patients with type 1 diabetes mellitus as it may increase the risk of diabetic ketoacidosis in these patients.
• Correct volume depletion prior to initiating treatment.
• This drug may need to be temporarily stopped prior to radiologic studies utilizing iodinated contrast materials or for surgical procedures when restricted food or fluid intake is expected; adequate renal function should be confirmed prior to restarting therapy.

• Assess renal function at baseline and as clinically indicated
• Assess fluid status prior to initiation and monitor for signs and symptoms of volume depletion during therapy
• Measure hematologic parameters annually; consider obtaining a serum vitamin B12 every 2 to 3 years
• Monitor glycemic control
• Evaluate for the presence of acidosis, including ketoacidosis in symptomatic patients even if blood sugar is less than 250 mg/dL.

• Read the US FDA-approved patient labeling (Medication Guide).
• Patients should be advised about the importance of regular glycemic monitoring and the need to seek medical advice during periods of stress as medical management of diabetes may change.
• Patients should be instructed to maintain adequate fluid intake.
• Patients should be instructed to report genital mycotic infections, urinary tract infections, or any unusual symptoms.
• Patients should be instructed to seek immediate medical attention for symptoms of tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, especially if they have a fever and are feeling unwell.
• Patients should be informed about the symptoms of lactic acidosis and ketoacidosis and conditions that might increase the risk of these occurring; they should understand when to contact their healthcare professional and when they should seek immediate medical attention.
• Advise patients that this drug may need to be temporarily stopped if undergoing radiologic studies with intravascular iodinated contrast materials or surgical procedures that will limit food or fluid intake.
• Advise patients on the risks of excessive alcohol intake.
• Advise patient to speak to physician or health care professional if pregnant, intend to become pregnant, or are breastfeeding; premenopausal women should understand there is a risk that treatment with metformin may lead to unintended pregnancy.