Description

Alogliptin is primarily renally excreted. Cytochrome (CYP) P450-related metabolism is negligible. No significant drug-drug interactions are observed with the CYP-substrates or inhibitors tested or with renally excreted drugs.

Common side effects are nasopharyngitis, headache and upper respiratory tract infection.

Pregnancy Category B. No adequate or well-controlled studies in pregnant women have been conducted with Alogliptin. Alogliptin tablets should be used during pregnancy only if clearly needed. It is not known whether Alogliptintin is excreted in human milk. caution should be exercised when Alogliptin is administered to a nursing woman.

Acute pancreatitis: If pancreatitis is suspected, promptly Alogliptin should be discontinued. Hypersensitivity: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with Alogliptin such as anaphylaxis, angioedema and severe cutaneous adverse reactions. In such cases, promptly Alogliptin should be discontinued. Hepatic effects: Postmarketing reports of hepatic failure, sometimes fatal. Causality can not be excluded. If liver injury is detected, promptly interrupt Alogliptin and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. Do not restart Alogliptin if liver injury is confirmed and no alternative etiology can be found. Hypoglycemia: When an insulin secretagogue (e.g. sulfonylurea) or insulin is used in combination with Alogliptin, a lower dose of the insulin secretagogue or insulin may be required to minimize the risk of hypoglycaemia. Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Alogliptin or any other antidiabetic drug.

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. 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.

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.

Dipeptidyl Peptidase-4 (DPP-4) inhibitor