Drug Detail:Empagliflozin and metformin (Empagliflozin and metformin [ em-pa-gli-floe-zin-and-met-for-min ])
Drug Class: Antidiabetic combinations
Usual Adult Dose for Diabetes Type 2
Individualize dosage based on patient's current regimen
Empagliflozin/metformin IMMEDIATE-RELEASE:
For Patients Already on Metformin:
- Initial dose: Switch to empagliflozin 10 mg/day plus similar total daily dose of metformin; give in 2 equally divided doses orally twice a day
- Initial dose: Switch to empagliflozin at the same total daily dose plus metformin 1000 mg/day; give in 2 equally divided doses orally twice a day
- Initial dose: Switch to same total daily dose of each component (or nearest appropriate dose of metformin); give in 2 equally divided doses orally twice a day
Maximum dose: empagliflozin: 25 mg/day; metformin: 2000 mg/day
Empagliflozin/metformin EXTENDED-RELEASE:
For Patients Already on Metformin:
- Initial dose: Switch to empagliflozin 10 mg plus similar total daily dose of metformin orally once a day
- Initial dose: Switch to empagliflozin at the same total daily dose plus metformin 1000 mg/day orally once a day
- Initial dose: Switch to same total daily dose of each component (or nearest appropriate dose of metformin) orally once a day
Maximum dose: empagliflozin: 25 mg/day; metformin: 2000 mg/day
Comments:
- 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.
- Assess renal function; correct volume depletion prior to beginning therapy.
Uses:
- 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 death in adults with type 2 diabetes mellitus and established cardiovascular disease.
Usual Adult Dose for Cardiovascular Risk Reduction
Individualize dosage based on patient's current regimen
Empagliflozin/metformin IMMEDIATE-RELEASE:
For Patients Already on Metformin:
- Initial dose: Switch to empagliflozin 10 mg/day plus similar total daily dose of metformin; give in 2 equally divided doses orally twice a day
- Initial dose: Switch to empagliflozin at the same total daily dose plus metformin 1000 mg/day; give in 2 equally divided doses orally twice a day
- Initial dose: Switch to same total daily dose of each component (or nearest appropriate dose of metformin); give in 2 equally divided doses orally twice a day
Maximum dose: empagliflozin: 25 mg/day; metformin: 2000 mg/day
Empagliflozin/metformin EXTENDED-RELEASE:
For Patients Already on Metformin:
- Initial dose: Switch to empagliflozin 10 mg plus similar total daily dose of metformin orally once a day
- Initial dose: Switch to empagliflozin at the same total daily dose plus metformin 1000 mg/day orally once a day
- Initial dose: Switch to same total daily dose of each component (or nearest appropriate dose of metformin) orally once a day
Maximum dose: empagliflozin: 25 mg/day; metformin: 2000 mg/day
Comments:
- 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.
- Assess renal function; correct volume depletion prior to beginning therapy.
Uses:
- 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 death in adults with type 2 diabetes mellitus and established cardiovascular disease.
Renal Dose Adjustments
eGFR less than 45 mL/min/1.73 m2: Initiation is not recommended
eGFR less than 30 mL/min/1.73 m2: 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; or 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 taken into account
Concomitant use with Cationic Drugs:
- Cationic drugs may reduce metformin elimination; monitor and adjust dose as needed
Concomitant Insulin or Insulin Secretagogue:
- Consider dose adjustment of insulin or insulin secretagogue to prevent hypoglycemia
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; or 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 is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities include elevated blood lactate (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), increased lactate/pyruvate ratio, and metformin plasma levels generally greater than 5 mcg/mL.
- Risk factors include renal impairment, concomitant use of certain drugs (e.g., cationic drugs 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 lactic acidosis and manage in high risk groups are provided in the full prescribing information.
- If metformin-associated lactic acidosis is suspected, immediately discontinue this drug and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.
CONTRAINDICATIONS:
- 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 empagliflozin, metformin, or any product ingredients
Safety and efficacy have not been established in patients younger than 18 years.
Consult WARNINGS section for additional precautions.
Dialysis
Contraindicated
Other Comments
Administration advice:
Immediate-release:
- Take orally twice a day with meals
- Take orally once a day with morning meal; swallow whole, do not split, crush, dissolve or chew before swallowing
- There have been reports of incompletely dissolved metformin ER tablets eliminated in the feces; if patient reports seeing tablets in feces, adequacy of glycemic control should be assessed
Missed dose: If a dose is missed, take as soon as remembered, but do not double next dose
General:
- This drug should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
- 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.
Monitoring:
- Assess renal function at baseline, repeat at least annually and more often in elderly patients or 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
- Monitor low-density lipoprotein levels during drug treatment.
- Evaluate for the presence of acidosis, including ketoacidosis in symptomatic patients even if blood sugar is less than 250 mg/dL.
Patient advice:
- 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 risk; 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 of unintended pregnancy with metformin use.
