Alogliptin and Pioglitazone

Alogliptin and pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Alogliptin and pioglitazone tablets are a combination of alogliptin, a dipeptidyl peptidase-4 inhibitor, and pioglitazone, a thiazolidinedione agonist of peroxisome proliferator receptor gamma, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: Alogliptin and pioglitazone tablets are not recommended for use in patients with type 1 diabetes mellitus.

Alogliptin and pioglitazone tablets combine two antihyperglycemic agents: alogliptin and pioglitazone. 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 dipeptidyl peptidase-4 (DPP-4) enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes mellitus, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved.

Obtain liver tests prior to initiation. Alogliptin and pioglitazone tablets may be taken with or without food. Individualize the starting dose of alogliptin and pioglitazone tablets based on the patient’s current regimen and concurrent medical condition but do not exceed a daily dose of alogliptin 25 mg and pioglitazone 45 mg. The recommended starting dosage in patients with NYHA Class I or II congestive heart failure is 25 mg of alogliptin and 15 mg of pioglitazone. Prior to initiation, assess renal function with creatinine clearance (CrCl). Mild renal impairment (creatinine clearance [CrCl] ≥60 mL/min): same as the recommended dosage in patients with normal renal function. Moderate renal impairment (CrCl ≥30 to <60 mL/min): 12.5 mg of alogliptin and 30 mg of pioglitazone once daily.

Alogliptin and pioglitazone tablets are contraindicated in patients with: Established NYHA Class III or IV heart failure at the time of alogliptin and pioglitazone tablets initiation. A history of serious hypersensitivity reaction to alogliptin, pioglitazone, or any of the excipients in alogliptin and pioglitazone tablets. Reactions such as anaphylaxis, angioedema and severe cutaneous adverse reactions have been reported. In patients with established NYHA Class III or IV heart failure at the time of alogliptin and pioglitazone tablets initiation.

Boxed warning (congestive heart failure): Thiazolidinediones, including pioglitazone, which is a component of alogliptin and pioglitazone tablets, cause or exacerbate congestive heart failure in some patients. After initiation of alogliptin and pioglitazone tablets and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea and/or edema). Congestive heart failure: Fluid retention may occur and can exacerbate or lead to congestive heart failure. Combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk. Consider the risks and benefits of alogliptin and pioglitazone tablets prior to initiating treatment in patients at risk for heart failure. Monitor patients for signs and symptoms. Pancreatitis: There have been postmarketing reports of acute pancreatitis.

The following serious adverse reactions are described below or elsewhere in the prescribing information: Congestive Heart Failure Pancreatitis Hypersensitivity Reactions Hepatic Effects Edema Fractures Urinary Bladder Tumors Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues Macular Edema Severe and Disabling Arthralgia Bullous Pemphigoid The most common adverse reactions (4% or greater incidence) are nasopharyngitis, back pain and upper respiratory tract infection.

Strong CYP2C8 inhibitors (e.g., gemfibrozil) increase pioglitazone concentrations. Limit the pioglitazone dose to 15 mg daily. CYP2C8 inducers (e.g., rifampin) may decrease pioglitazone concentrations. Topiramate may decrease pioglitazone concentrations.

Store at 25°C (77°F), excursions permitted to 15° to 30°C (59° to 86°F). Keep container tightly closed and protect from moisture and humidity.