Usual Adult Dose for Diabetes Type 2

• To Improve Glycemic Control for Patients Not Already Taking Dapagliflozin:

Initial dose:
Dapagliflozin 5 mg plus current metformin dose orally once a day

• For indications related to heart failure:
• Initial dose:

Dapagliflozin 10 mg plus current metformin dose orally once a day

Maximum dose: Dapagliflozin 10 mg-metformin 2000 mg per day

Comments:

• Adjust doses based on effectiveness and tolerability.
• Patients taking an evening dose of metformin XR should skip their last dose before starting this drug; take this drug once daily in the morning with food.
• When used in combination with insulin or insulin secretagogue, a lower dose of insulin or insulin secretagogue may be considered to reduce the risk of hypoglycemia.

Uses:

• As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• Dapagliflozin is indicated to reduce:
• The risk of hospitalization for heart failure in patients with type 2 diabetes mellitus and established cardiovascular disease or multiple cardiovascular risk factors.
• The risk of cardiovascular death and hospitalization for heart failure in adults with type 2 diabetes mellitus and heart failure (NYHA class II-IV) with reduced ejection fraction.

Usual Adult Dose for Heart Failure

• To Improve Glycemic Control for Patients Not Already Taking Dapagliflozin:

Initial dose:
Dapagliflozin 5 mg plus current metformin dose orally once a day

• For indications related to heart failure:
• Initial dose:

Dapagliflozin 10 mg plus current metformin dose orally once a day

Maximum dose: Dapagliflozin 10 mg-metformin 2000 mg per day

Comments:

• Adjust doses based on effectiveness and tolerability.
• Patients taking an evening dose of metformin XR should skip their last dose before starting this drug; take this drug once daily in the morning with food.
• When used in combination with insulin or insulin secretagogue, a lower dose of insulin or insulin secretagogue may be considered to reduce the risk of hypoglycemia.

Uses:

• As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• Dapagliflozin is indicated to reduce:
• The risk of hospitalization for heart failure in patients with type 2 diabetes mellitus and established cardiovascular disease or multiple cardiovascular risk factors.
• The risk of cardiovascular death and hospitalization for heart failure in adults with type 2 diabetes mellitus and heart failure (NYHA class II-IV) with reduced ejection fraction.

Renal Dose Adjustments

eGFR 45 mL/min/1.73 m2 or greater: No adjustment recommended.
eGFR 30 to less than 45 mL/min/1.73 m2: Use is not recommended.
eGFR less than 30 mL/min/1.73 m2: Contraindicated

Liver Dose Adjustments

Not recommended in patients with hepatic impairment.

Dose Adjustments

Therapeutic drug monitoring/range: Steady-state plasma concentrations of metformin are achieved within 24 to 48 hours and are less than 1 mcg/mL; metformin levels greater than 5 mcg/mL have been implicated as the cause of lactic acidosis.

Iodinated Contrast Imaging Procedures:

• In patients with a history of liver disease, alcoholism, or heart failure: this drug should be stopped at time of, or prior to an iodinated contrast imaging procedure.
• In patients who will be administered intra-arterial iodinated contrast: this drug should be stopped at the time of, or prior to the procedure.

RESTART: Renal function should be reevaluated 48 hours after the imaging procedure and if renal function is stable this drug may be restarted.

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 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 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 measure in a hospital setting. Prompt hemodialysis is recommended.

CONTRAINDICATIONS:

• Hypersensitivity to either active component or to any of the ingredients
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma
• Severe renal impairment (eGFR less than 30 mL/min/1.73 m2), ESRD or dialysis

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:

• Take orally once a day in the morning with food.
• Swallow whole; do not crush, cut, or chew XR tablets.
• XR tablet shells may appear in feces as a soft mass that may resemble the original tablet.
• For patient requiring dapagliflozin 5 mg/metformin 2000 mg; use 2 of the dapagliflozin 2.5 mg/metformin 1000 mg oral tablets.

Storage requirements:
Store at 20C to 25C (68F to 77F); excursions permitted between 15C and 30C (59F and 86F).

General:

• Not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
• Correct volume depletion prior to initiating treatment.
• Temporarily stop treatment prior to radiologic studies utilizing iodinated contrast materials in patients with a history of liver disease, alcoholism, or heart failure, and in all patients who will be administered intra-arterial iodinated contrast; may resume after 48-hours once adequate renal function is confirmed.
• Assess renal function more frequently in elderly patients.

Monitoring:

• Cardiovascular: Hypotension
• Hypersensitivity: Hypersensitivity reactions
• Infection: Genital mycotic infections
• Assess fluid status prior to initiation and monitor for signs and symptoms of volume depletion during therapy.
• Obtain eGFR prior to initiating treatment, repeat at least annually or more often as clinically indicated.
• Measure hematologic parameters annually; consider obtaining a serum Vitamin B12 every 2 to 3 years.
• When unexplained non-specific symptoms develop (e.g., nausea, vomiting, abdominal pain, tiredness, and labored breathing) assess for lactic acidosis and ketoacidosis, regardless of blood sugar level.

Patient advice:

• Instruct patient to read the US FDA-approved patient labeling (Medication Guide).
• Patients should understand that this drug will cause the urine to test positive for glucose.
• Patients should understand that tablet shells may appear in feces, and this should not cause alarm.
• Patients should be instructed to ensure adequate fluid intake to avoid adverse reactions related to volume depletion such as orthostatic hypotension.
• Patients should be instructed to seek medical advice during periods of stress as medical management of diabetes may change.
• Inform patients that genital mycotic infections, urinary tract infections, and hypersensitivity reactions may occur; patients should be instructed to contact their health care professional.
• 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 experiencing symptoms of ketoacidosis such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue, or sleepiness should be instructed to seek immediate medical attention.
• Inform patients about the risk of lactic acidosis, conditions that might predispose them to its occurrence, and symptoms to watch for and report.
• Advise patient that this drug will 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.
• Tell patients that while gastrointestinal symptoms might be common when initiating treatment, gastrointestinal problems after initiation should be reported.
• Inform patients to inform their healthcare provider if pregnant or planning to become pregnant.
• This drug is not recommended while breastfeeding.

Frequently asked questions

• What are the ingredient drugs contained in Qternmet XR?