Usual Adult Dose for Diabetes Type 2

Individualize initial dose based on patients current regimen; metformin dose should be gradually titrated upwards and taken with food to reduce the gastrointestinal side effects:

Initial dose: alogliptin 12.5 mg-metformin 500 mg OR alogliptin 12.5 mg-metformin 1000 mg orally twice a day
Maintenance dose: Adjust dose based on efficacy and tolerability
Maximum dose: alogliptin 25 mg-metformin 2000 mg per day

Comments:

• When used in combination with insulin or insulin secretagogues such as sulfonylureas, a lower dose of insulin or the insulin secretagogue may be required to minimize the risk of hypoglycemia.

Renal Dose Adjustments

Mild renal impairment (eGFR greater than 60 mL/min/1.73 m2): No dose adjustments recommended
Moderate renal impairment (eGFR 30 to 60 mL/min/1.73 m2): Not recommended because alogliptin dose in combination product is not appropriate
Severe renal impairment (estimated GFR less than 30 mL/min/1.73 m2): Contraindicated

IODINATED CONTRAST PROCEDURE:

• For patients receiving intra-arterial iodinated contrast, this drug should be stopped and restarted only if renal function is stable.

Liver Dose Adjustments

Hepatic impairment: Use not recommended

• If liver injury is detected, promptly interrupt therapy and assess for probable cause.
• If liver injury is confirmed and no alternative etiology is found, do not restart this drug.

Dose Adjustments

Elderly: No dose adjustment is necessary based on age; however, ensure adequate renal function before initiating therapy.

Due to risk of hypoglycemia if used in combination with insulin, or insulin secretagogue such as a sulfonylurea, a lower dose of insulin, or insulin secretagogue should be considered to decrease the risk of hypoglycemia.

IODINATED CONTRAST PROCEDURE:

• Stop this drug at time of, or prior to, an iodinated contrast imaging procedure for patients with an eGFR between 30 and 60 mL/min/1.73 m2.
• Stop this drug in any patient who will be administered intra-arterial iodinated contrast.
• Stop this drug in any patient with a history of hepatic impairment, alcoholism, or heart failure.
• 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. The 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 is characterized by elevated blood lactate levels (greater than 5 mmol/L), anion gap, acidosis (without evidence of ketonuria or ketonemia) and 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 or older, 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 high risk groups are provided in the full prescribing information.
• If metformin-associated lactic acidosis is suspected, immediately discontinue therapy and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

• History of a serious hypersensitivity reaction to alogliptin or metformin, such as anaphylaxis, angioedema, or severe cutaneous adverse reactions
• Severe renal impairment (eGFR less than 30 mL/min/1.73 m2)
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis

Dialysis

Data not available

Other Comments

Administration advice:

• Take orally twice a day with meals
• Swallow whole, do not split tablets before swallowing
• If a dose is missed, do not double the next dose

• Consider risks and benefits of using this therapy in patients with risk factors for heart failure.
• Use of metformin in premenopausal anovulatory females may result in an unintended pregnancy due to its effects on ovulation.
• May need to 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.

• Monitor glycemic control
• Renal: Assess renal function at baseline and annually; more frequent monitoring is recommended in patients with serum creatinine levels at the upper limit of normal, elderly patients, and for patients at risk for developing renal impairment
• Hematologic: Measure hematologic parameters annually
• Hepatic: Obtain liver function tests prior to initiating treatment; monitor for signs and symptoms of liver dysfunction
• Monitor for signs and symptoms of pancreatitis
• Monitor for signs and symptoms of heart failure

• Patients should be instructed to read the US FDA-approved patient labeling (Medication Guide).
• Instruct patient to report signs and symptoms of pancreatitis; if persistent, severe abdominal pain occurs, seek medical advice promptly.
• Instruct patients to discontinue therapy and seek medical advice for symptoms of allergic reaction including skin rash, hives, and swelling of the face, lips, tongue, and throat.
• Instruct patients to report signs and symptoms of heart failure and hepatic dysfunction
• 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 or if blisters or erosions occur on skin.