Alogliptin and Metformin

Alogliptin and metformin HCl tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Alogliptin and metformin HCl tablets are a combination of alogliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor and metformin hydrochloride (HCl), a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: Should not be used in patients with type 1 diabetes mellitus. Limitations of Use Alogliptin and metformin HCl tablets should not recommended for use in patients with type 1 diabetes mellitus.

Alogliptin and Metformin HCl Alogliptin and metformin HCl tablets combines two antihyperglycemic agents with complementary and distinct mechanisms of action to improve glycemic control in patients with type 2 diabetes mellitus: alogliptin, a selective inhibitor of DPP-4, and metformin HCl, a member of the biguanide class. Alogliptin Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP-4 enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production.

Individualize the starting dosage based on the patient's current regimen. Given orally twice daily with food. Adjust the dosage based on effectiveness and tolerability while not exceeding the maximum recommended daily dosage of 25 mg alogliptin and 2000 mg metformin HCl. Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR). Do not use in patients with eGFR below 60 mL/min/1.73 m 2. Alogliptin and metformin HCl tablets may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures.

Alogliptin and metformin HCl tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ). Acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma. History of serious hypersensitivity reaction to alogliptin or metformin or any of the excipients in alogliptin and metformin HCl tablets, such as anaphylaxis, angioedema and severe cutaneous adverse reactions. Severe renal impairment: eGFR below 30 mL/min/1.73 m 2. Metabolic acidosis including diabetic ketoacidosis. History of serious hypersensitivity to alogliptin or metformin, components of Alogliptin and metformin HCl tablets or any of the excipients.

Boxed warning (lactic acidosis): Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmia's. 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. Lactic Acidosis: See boxed warning. Pancreatitis: There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue alogliptin and metformin HCl tablets. Heart Failure: Consider the risks and benefits of alogliptin and metformin HCl tablets prior to initiating treatment in patients at risk for heart failure. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of alogliptin and metformin HCl tablets.

The following serious adverse reactions are described below or elsewhere in the prescribing information: Pancreatitis Heart Failure Hypersensitivity Reactions Hepatic Effects Severe and Disabling Arthralgia Bullous Pemphigoid Most common adverse reactions (incidence ≥4%) are upper respiratory tract infection, nasopharyngitis, diarrhea, hypertension, headache, back pain and urinary tract infection.

Carbionic anhydrase inhibitors may increase risk of lactic acidosis. Consider more frequent monitoring. Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine), may increase the accumulation of metformin. Consider the benefits and risks of concomitant use. Alcohol can potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake. Metformin HCl Carbonic Anhydrase Inhibitors Clinical Impact: Carbonic anhydrase inhibitors frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with ALOGLIPTIN WITH METFORMIN HCl TABLETS may increase the risk of lactic acidosis. Intervention: Consider more frequent monitoring of these patients.

Store at 25°C (77°F), excursions permitted to 15° to 30°C (59° to 86°F).