Alogliptin

Indications

Alogliptin is indicated for use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It can be used as monotherapy or in combination with other antidiabetic medications, including metformin, sulfonylureas, thiazolidinediones, or insulin.

Pharmacology

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. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Alogliptin is a DPP-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus. Alogliptin selectively binds to and inhibits DPP-4 but not DPP-8 or DPP-9 activity in vitro at concentrations approximating therapeutic exposures.

Dosage And Administration

The recommended dosage of alogliptin is 25 mg once daily with or without food.

Patients with Renal Impairment:

  • No dose adjustment of Alogliptin is necessary for patients with mild renal impairment (creatinine clearance ≥60 mL/min).
  • The dose of Alogliptin is 12.5 mg once daily for patients with moderate renal impairment (creatinine clearance ≥30 to <60 mL/min).
  • The dose of Alogliptin is 6.25 mg once daily for patients with severe renal impairment (creatinine clearance ≥15 to <30 mL/min) or with end-stage renal disease (ESRD) (creatinine clearance <15 mL/min or requiring hemodialysis).

Patients requiring hemodialysis can receive their dose of alogliptin without regard to the timing of the dialysis.

Interaction

Alogliptin is primarily renally excreted, and CYP-450–related metabolism is negligible. Alogliptin is not an inducer or inhibitor of CYP-450 enzymes.1 Clinically relevant interactions have not been observed with the CYP substrates or inhibitors tested or with renally excreted drugs.

Contraindications

Alogliptin is contraindicated in patients with a history of serious hypersensitivity reactions, such as anaphylaxis, angioedema, or severe cutaneous adverse reactions, to alogliptin-containing products.

Side Effects

The most common side effects of alogliptin are headaches, indigestion, diarrhoea and skin rashes. Adverse events include mild hypoglycemia based on clinical studies. Alogliptin may also cause joint pain that can be severe and disabling. In April 2016, the U.S. Food and Drug Administration (FDA) added a warning about increased risk of heart failure.

Pregnancy And Lactation

Use in Pregnancy: Alogliptin is in Pregnancy Category B. Abnormalities were not observed in animal models; however, placental transfer to the fetus was observed. Alogliptin should be used in pregnancy only if clearly needed.

Use in Lactation: Alogliptin is secreted in the milk of lactating rats in a 2:1 ratio to plasma. It is not known whether it is excreted in human milk. Caution is advised if alogliptin is administered to a breastfeeding woman.

Precautions And Warnings

Pancreatitis: Acute pancreatitis has been reported in patients receiving alogliptin therapy. Patients should be monitored for signs and symptoms of pancreatitis, and therapy should be discontinued if pancreatitis is suspected. It is unknown whether patients with a history of pancreatitis have an increased risk of developing pancreatitis while receiving alogliptin.

Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, angioedema, and severe cutaneous reactions including Stevens-Johnson syndrome, have been observed in patients receiving alogliptin therapy. It is unknown whether patients with a history of angioedema with another DPP-4 inhibitor will be predisposed to angioedema with alogliptin.

Heart Failure: Consider the risks and benefits of alogliptin prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment, and observe these patients for signs and symptoms of heart failure during therapy. Patients should be advised of the characteristic symptoms of heart failure and should be instructed to immediately report such symptoms. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of alogliptin.

Insulin and insulin secretagogues, such as sulfonylureas, are known to cause hypoglycemia. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with angioedema.

Overdose Effects

The highest doses of Alogliptin administered in clinical trials were single doses of 800 mg to healthy subjects and doses of 400 mg once daily for 14 days to patients with type 2 diabetes (equivalent to 32 times and 16 times the maximum recommended clinical dose of 25 mg, respectively). No serious adverse events were observed at these doses. In the event of an overdose, it is reasonable to institute the necessary clinical monitoring and supportive therapy as dictated by the patient's clinical status. Per clinical judgment, it may be reasonable to initiate removal of unabsorbed material from the gastrointestinal tract. Alogliptin is minimally dialyzable; over a 3-hour hemodialysis session, approximately 7% of the drug was removed. Therefore, hemodialysis is unlikely to be beneficial in an overdose situation. It is not known if Alogliptin is dialyzable by peritoneal dialysis.

Therapeutic Class

Dipeptidyl Peptidase-4 (DPP-4) inhibitor

Use in special populations

Pediatric Use: Safety and effectiveness of Alogliptin in pediatric patients have not been established.

Geriatric Use: Of the total number of patients (N=8507) in clinical safety and efficacy studies treated with Alogliptin, 2064 (24.3%) patients were 65 years and older and 341 (4%) patients were 75 years and older. No overall differences in safety or effectiveness were observed between patients 65 years and over and younger patients. While this clinical experience has not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.

Hepatic Impairment: No dose adjustments are required in patients with mild to moderate hepatic impairment (Child-Pugh Grade A and B) based on insignificant change in systemic exposures (e.g., AUC) compared to subjects with normal hepatic function in a pharmacokinetic study. Alogliptin has not been studied in patients with severe hepatic impairment (Child-Pugh Grade C). Use caution when administering Alogliptin to patients with liver disease.

Storage Conditions

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Available Brand Names