Usual Adult Dose for Diabetes Type 2

Individualize dose based patient's current regimen, effectiveness, and tolerability; gradual dose titration of metformin is advised to reduce gastrointestinal side effects.

Saxagliptin-Metformin XR:
Usual dose: 1 tablet orally once a day with the evening meal
Maximum dose: saxagliptin 5 mg-metformin 2000 mg orally once a day
Maximum dose with concomitant strong CYP450 3A4/5 inhibitors: saxagliptin 2.5-metformin 1000 mg orally once a day

• Patients not currently treated with metformin: Initial dose saxagliptin 5 mg-metformin 500 mg orally once daily
• Patients currently treated with metformin: Initial dose: saxagliptin 5 mg plus the dose of metformin that is already being taken, or the nearest therapeutically appropriate dose.

Comments:

• Patients requiring saxagliptin 2.5 mg per day AND are either metformin-naive or require a dose of metformin greater than 1000 mg per day should use the individual components.
• Following a switch from metformin immediate-release to metformin extended release, glycemic control should be closely monitored and dosage adjustments made according.
• When used in combination with a sulfonylurea or insulin, a lower dose of the sulfonylurea or insulin may be considered to reduce the risk of hypoglycemia.
• Note: There are saxagliptin-metformin combination products available internationally that contain immediate-release metformin; saxagliptin-metformin products containing immediate-release metformin should be dosed twice a day.

Use: An adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes when treatment with both saxagliptin and metformin is appropriate.

Renal Dose Adjustments

Renal impairment: Contraindicated (e.g. serum creatinine levels 1.5 mg/dL or greater in men; 1.4 mg/dL or greater in women, or abnormal CrCl)

New Metformin Renal Dosing: Obtain eGFR prior to initiating therapy:

• eGFR less than 30 mL/min/1.73 m2: Use is contraindicated
• eGFR 30 to 45 mL/min/1.73 m2: Initiating therapy is not recommended
• eGFR that falls below 30 mL/min/1.73 m2 during therapy: Discontinue therapy
• eGFR that falls below 45 mL/min/1.73 m2 during therapy: Assess risks versus benefit of continued therapy
• eGFR greater than 45 mL/min/1.73 m2: No dose adjustments recommended

Saxagliptin:
Mild renal dysfunction (CrCl more than 50 mL/min): No adjustment recommended.
Moderate or severe renal dysfunction (CrCl 50 mL/min or less): 2.5 mg orally once a day, regardless of meals

IODINATED CONTRAST PROCEDURE:

• For patients with eGFR between 30 and 60 mL/min/1.73 m2: Stop this drug at the time of, or before imaging procedure; re-evaluate eGFR 48 hours after procedure; restart therapy only if renal function is stable.

• Use is contraindicated in conditions that may result in renal impairment such as cardiovascular collapse (shock), acute myocardial infarction, and septicamia; regular renal function monitoring is recommended to reduce the risk of developing lactic acidosis
• Treatment should not be initiated in patients 80 years or older unless measurement of CrCl demonstrates that renal function is not reduced.

Liver Dose Adjustments

Not recommended

Dose Adjustments

• When used in combination with a sulfonylurea or insulin, a lower dose of the sulfonylurea or insulin may be considered to reduce the risk of hypoglycemia.

Saxagliptin-metformin should be temporarily discontinued at the time of or prior to radiologic studies utilizing intravascular administration of iodinated contrast materials, withheld for 48 hours post procedure, and restarted once renal function has been confirmed as normal.

Precautions

US BOXED WARNINGS: Lactic acidosis is a rare, but serious, complication that can occur due to metformin accumulation.

• The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure.
• The onset of lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgia, respiratory distress, increasing somnolence, and nonspecific abdominal distress.
• Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate.
• If acidosis is suspected, discontinue saxagliptin-metformin and hospitalize the patient immediately.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Take orally once daily with the evening meal
• Swallow whole, do not crush, cut, or chew
• Occasionally, a mass resembling the original tablet may be eliminated in the feces.
• If a dose is missed, take the next dose as prescribed; patients should not take an extra dose the next day

General:

• Consider risks and benefit of therapy in patients with risk factory for heart failure,
• Temporarily stop treatment prior to radiologic studies utilizing iodinated contrast materials and for surgical procedures when restricted food or fluid intake is expected; may resume once adequate renal function is confirmed.
• This drug is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis as it would not be effective in these settings.

Monitoring:

• Monitor glycemic control
• Cardiovascular: Signs and symptoms of heart failure
• Renal: Assess renal function baseline and annually; in patients with serum creatinine levels at the upper limit of normal, elderly patients, and in patients at risk for developing renal impairment, more frequent monitoring is recommended.
• Hematologic: Measure hematologic parameters annually
• Monitor for signs and symptoms of pancreatitis

Patient advice:

• Instruct patient to report signs and symptoms of pancreatitis; if persistent, severe abdominal pain occurs, seek medical advice promptly.
• Instruct patients on the signs and symptoms of heart failure and have them report any occurrence of these events to health care provider promptly.
• Hypoglycemia may occur, more commonly when used in combination with insulin or a sulfonylurea.
• Patients should understand the importance of adhering to dietary instructions and regular physical activity; during periods of stress such as fever, trauma, infection, or surgery, management of diabetes may change and patients should be advised to seek medical advice.
• 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.
• Instruct patients to contact their health care provider if they develop severe and persistent joint pain.

Frequently asked questions

• What are the ingredient drugs contained in Qternmet XR?