Empagliflozin / Metformin Dosage

Medically reviewed by Drugs.com. Last updated on Oct 4, 2023.

Applies to the following strengths: 5 mg-500 mg; 12.5 mg-1000 mg; 5 mg-1000 mg; 12.5 mg-500 mg; 10 mg-1000 mg; 25 mg-1000 mg

Usual Adult Dose for Diabetes Type 2

IMMEDIATE-RELEASE TABLETS:
Initial Dose: Empagliflozin 5 mg orally twice a day

For Additional Glycemic Control:

Empagliflozin may be increased to a maximum of 12.5 mg orally twice a day if 10 mg/day is tolerated.
Metformin may be increased to a maximum of 1000 mg orally twice a day.

When Switching to This Combination Drug:

In patients already taking metformin: Should start at empagliflozin 10 mg/day and a similar total daily dosage of metformin, administered in 2 equally divided doses orally twice a day
In patients already taking empagliflozin: Should start at the same total daily dosage of empagliflozin and metformin 1000 mg/day, administered in 2 equally divided doses orally twice a day
In patients already taking empagliflozin and metformin: Should start at the same total daily dosage of each component, administered in 2 equally divided doses orally twice a day

EXTENDED-RELEASE TABLETS:
Initial Dose: Empagliflozin 10 mg orally once a day

For Additional Glycemic Control:

Empagliflozin may be increased to a maximum of 25 mg orally once a day if 10 mg/day is tolerated.
Metformin may be increased to a maximum of 2000 mg orally once a day.

When Switching to This Combination Drug:

In patients already taking metformin: Should start at empagliflozin 10 mg/day and a similar total daily dosage of metformin, administered orally once a day
In patients already taking empagliflozin: Should start at the same total daily dosage of empagliflozin and metformin 1000 mg/day, administered orally once a day
In patients already taking empagliflozin and metformin: Should start at the same total daily dosage of each component, administered orally once a day

Comments:

Immediate-release tablets should be administered orally twice a day with meals (i.e., total daily dosage divided into 2 equal doses/day).
Extended-release tablets should be administered orally once a day with a meal in the morning.
Gradual dose escalation is recommended to reduce gastrointestinal adverse reactions with metformin.

Uses:

As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus
Empagliflozin (when used as a component of this combination drug):
To reduce the risk of cardiovascular death in patients with type 2 diabetes mellitus and established cardiovascular disease
To reduce the risk of cardiovascular death and hospitalization for heart failure in patients with type 2 diabetes mellitus and heart failure

Usual Adult Dose for Cardiovascular Risk Reduction

IMMEDIATE-RELEASE TABLETS:
Initial Dose: Empagliflozin 5 mg orally twice a day

For Additional Glycemic Control:

Empagliflozin may be increased to a maximum of 12.5 mg orally twice a day if 10 mg/day is tolerated.
Metformin may be increased to a maximum of 1000 mg orally twice a day.

When Switching to This Combination Drug:

In patients already taking metformin: Should start at empagliflozin 10 mg/day and a similar total daily dosage of metformin, administered in 2 equally divided doses orally twice a day
In patients already taking empagliflozin: Should start at the same total daily dosage of empagliflozin and metformin 1000 mg/day, administered in 2 equally divided doses orally twice a day
In patients already taking empagliflozin and metformin: Should start at the same total daily dosage of each component, administered in 2 equally divided doses orally twice a day

EXTENDED-RELEASE TABLETS:
Initial Dose: Empagliflozin 10 mg orally once a day

For Additional Glycemic Control:

Empagliflozin may be increased to a maximum of 25 mg orally once a day if 10 mg/day is tolerated.
Metformin may be increased to a maximum of 2000 mg orally once a day.

When Switching to This Combination Drug:

In patients already taking metformin: Should start at empagliflozin 10 mg/day and a similar total daily dosage of metformin, administered orally once a day
In patients already taking empagliflozin: Should start at the same total daily dosage of empagliflozin and metformin 1000 mg/day, administered orally once a day
In patients already taking empagliflozin and metformin: Should start at the same total daily dosage of each component, administered orally once a day

Comments:

Immediate-release tablets should be administered orally twice a day with meals (i.e., total daily dosage divided into 2 equal doses/day).
Extended-release tablets should be administered orally once a day with a meal in the morning.
Gradual dose escalation is recommended to reduce gastrointestinal adverse reactions with metformin.

Uses:

As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus
Empagliflozin (when used as a component of this combination drug):
To reduce the risk of cardiovascular death in patients with type 2 diabetes mellitus and established cardiovascular disease
To reduce the risk of cardiovascular death and hospitalization for heart failure in patients with type 2 diabetes mellitus and heart failure

Usual Pediatric Dose for Diabetes Type 2

Immediate-Release Tablets:
10 years and older:

Initial dose: Dosage should be individualized based on patient's current regimen.
Maintenance dose: Efficacy and tolerability should be monitored and the dosage adjusted as appropriate.
Maximum dose: Empagliflozin 25 mg/day and metformin 2000 mg/day

Comments:

This drug should be administered orally twice a day with meals (i.e., total daily dosage divided into 2 equal doses/day).
Gradual dose escalation is recommended to reduce gastrointestinal adverse reactions with metformin.

Use: As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus

Renal Dose Adjustments

Estimated GFR less than 45 mL/min/1.73 m2: Initiation is not recommended (due to metformin component).
Estimated GFR less than 30 mL/min/1.73 m2 or end-stage renal disease: Contraindicated

If iodinated contrast imaging procedure is needed during therapy:

In patients with estimated GFR less than 60 mL/min/1.73 m2: This drug should be discontinued at the time of, or prior to, the procedure.
Estimated GFR should be reevaluated 48 hours after the procedure.
This drug should be restarted if renal function is stable.

Comments:

Empagliflozin: The glucose lowering benefit of empagliflozin 25 mg decreased in adult patients with worsening renal function; risks of renal dysfunction, volume depletion adverse reactions, and urinary tract infection-related adverse reactions increased with worsening renal function. Pediatric patients (aged 10 to 17 years with type 2 diabetes mellitus) with estimated GFR less than 60 mL/min/1.73 m2 were not studied.
Metformin: This drug is substantially excreted by the kidney; the risk of metformin accumulation and lactic acidosis increases with the degree of renal dysfunction.

Liver Dose Adjustments

Liver dysfunction (including clinical or laboratory evidence of liver disease): Not recommended

If iodinated contrast imaging procedure is needed during therapy:

In patients with history of liver disease: This drug should be discontinued at the time of, or prior to, the procedure.
Estimated GFR should be reevaluated 48 hours after the procedure.
This drug should be restarted if renal function is stable.

Comments:

Metformin has been associated with some cases of lactic acidosis in patients with liver dysfunction.

Dose Adjustments

Iodinated Contrast Imaging Procedures:

In patients with history of alcoholism or heart failure, and in patients who will be administered intra-arterial iodinated contrast: This drug should be discontinued at the time of, or prior to, the procedure.
Estimated GFR should be reevaluated 48 hours after the procedure.
This drug should be restarted if renal function is stable.

Surgery:

This drug should be withheld for at least 3 days, if possible, before major surgery or procedures associated with prolonged fasting.
This drug should resume when the patient is clinically stable and has restarted oral intake.

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 (e.g., malaise, myalgias, respiratory distress, somnolence, abdominal pain). Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (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 dysfunction, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years or older, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute CHF), excessive alcohol intake, and liver dysfunction. The manufacturer product information should be consulted for steps to reduce the risk of and manage lactic acidosis in these high risk groups. If metformin-associated lactic acidosis is suspected, this drug should be discontinued immediately and general supportive measures should be started at once in a hospital setting; prompt hemodialysis is recommended.

CONTRAINDICATIONS:

Severe renal dysfunction (estimated GFR less than 30 mL/min/1.73 m2), end-stage renal disease, or dialysis
Acute or chronic metabolic acidosis (including diabetic ketoacidosis)
Hypersensitivity to either active component or to any of the ingredients

Immediate-release: Safety and efficacy have not been established in patients younger than 10 years.
Extended-release: 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:

Before starting this drug and as clinically indicated, assess renal function.
Assess volume status; in patients with volume depletion, correct this condition before starting this drug.
Immediate-release tablets: Administer twice a day with meals.
Extended-release tablets: Administer once a day with a meal in the morning. Swallow each tablet whole; do not split, crush, dissolve, or chew.
If a dose is missed, instruct patients to take the missed dose as soon as possible; advise patients not to double their next dose.

Storage requirements:

Store at 20C to 25C (68C to 77F); excursions permitted to 15C to 30C (59F to 86F).

General:

Limitations of Use:
This drug is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus; it may increase the risk of diabetic ketoacidosis in these patients.
Because of the metformin component, the use of this drug is limited to patients with type 2 diabetes mellitus for all indications.
Reactions such as angioedema have occurred with this drug.

Monitoring:

Hematologic: Hematologic parameters (annually)
Infections/infestations: For genital mycotic infections; for signs/symptoms of diabetic foot infection, including osteomyelitis (during therapy)
Metabolic: For signs/symptoms of volume depletion (after starting therapy); for ketoacidosis; ketones; blood glucose levels; vitamin B12 (every 2 to 3 years during therapy)
Musculoskeletal: For new pain/tenderness or sores/ulcers involving the lower limbs (during therapy)
Renal: Renal function (before and during therapy as clinically indicated; more often in older adult patients); estimated GFR (before starting and at least annually during therapy)

Patient advice:

Read the US FDA-approved patient labeling (Medication Guide).
Stop this drug immediately and notify your health care provider promptly if unexplained hyperventilation, malaise, myalgia, unusual somnolence, or other nonspecific symptoms occur.
Do not consume excessive alcohol.
Regular testing of renal function and regular hematological parameters during therapy are important.
Notify your health care provider that you are taking this drug before any surgical or radiological procedure.
You may be asked to monitor ketones; if symptoms consistent with ketoacidosis (including nausea, vomiting, abdominal pain, tiredness, and labored breathing) occur, discontinue this drug and seek medical attention at once. Blood glucose may be normal in the presence of ketoacidosis.
Contact your health care provider if symptomatic hypotension occurs; because dehydration may increase the risk for hypotension, maintain adequate fluid intake.
Seek medical advice if symptoms of urinary tract infections occur.
Promptly seek medical attention if you develop pain/tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, as well as fever above 100.4F or malaise.
Routine preventative foot care is important. Monitor for new pain or tenderness, sores or ulcers, or infections involving the leg or foot; seek medical advice immediately if such signs/symptoms develop.
Report any skin reaction or angioedema immediately and discontinue this drug until you have consulted prescribing health care provider.
Report pregnancy to your health care provider as soon as possible.
Do not breastfeed during therapy.
Extended-release tablets: Swallow whole; do not split, crush, dissolve, or chew. Incompletely dissolved tablets may be eliminated in the feces.
Take this drug only as prescribed.