Alogliptindosage

Obtain liver tests prior to initiation. OSENI may be taken with or without food. Individualize the starting dose of OSENI 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. Severe renal impairment (CrCl ≥15 to <30 mL/min) or ESRD (CrCl <15 mL/min or requiring hemodialysis): not recommended.

2.1 Important

Dosage and Administration Information Obtain liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) prior to initiating OSENI. Take OSENI orally once daily. Do not split tablets. OSENI may be taken with or without food. If a dose is missed, do not double the next dose.

2.2 Recommended

Dosage and Administration Recommended Starting Dosage Based on Current Regimen Individualize the starting dosage of OSENI based on the patient's current regimen and the available strengths of OSENI (see Table 1 ).

Table 1: Recommended Starting Dosage Based on the Patient’s Current Regimen Current Regimen Starting Dosage of OSENI (alogliptin/pioglitazone) For dosage recommendations for patients with renal impairment and/or congestive heart failure,. Not treated with either alogliptin or pioglitazone 25 mg/15 mg or 25 mg/30 mg Alogliptin 25 mg/15 mg or 25 mg/30 mg Pioglitazone 25 mg/15 mg, 25 mg/30 mg, or 25 mg/45 mg Alogliptin and pioglitazone Select a dosage that is as close as possible to the current dosage of alogliptin and pioglitazone Dosage Titration for Additional Glycemic Control Titrate the OSENI dosage gradually, as needed, after assessing therapeutic response and tolerability, up to a maximum dosage of 25 mg of alogliptin and 45 mg of pioglitazone once daily.

2.3 Recommended

Dosage for Patients with Renal Impairment Assess renal function prior to initiation of OSENI and periodically thereafter. The recommended dosage of OSENI in patients with mild renal impairment (creatinine clearance [CrCl] ≥60 mL/min) is the same as the recommended dosage in patients with normal renal function. The recommended dosage of OSENI for patients with moderate renal impairment (CrCl ≥30 to <60 mL/min) is 12.5 mg of alogliptin and 30 mg of pioglitazone once daily. OSENI is not recommended for patients with severe renal impairment (CrCl ≥15 to <30 mL/min) or ESRD (CrCl <15 mL/min or requiring hemodialysis) because these patients require a lower dosage of alogliptin than what is available in the fixed dose combination product, OSENI.

2.4 Recommendations for

Congestive Heart Failure Starting Dosage in Patients with NYHA Class I or II Congestive Heart Failure For patients with preexisting NYHA Class I or II congestive heart failure, the recommended starting dosage of OSENI is 25 mg of alogliptin and 15 mg of pioglitazone. Monitoring for Fluid Retention and Dosage Modifications for Congestive Heart Failure After initiation of OSENI or with dosage increase, monitor patients carefully for adverse reactions related to fluid retention as has been seen with pioglitazone (e.g., weight gain, edema and signs and symptoms of congestive heart failure). If congestive heart failure develops while taking OSENI, consider discontinuation of OSENI or dosage reduction of pioglitazone in OSENI.

2.5 Coadministration with

Strong CYP2C8 Inhibitors The maximum recommended dosage of OSENI is 25 mg of alogliptin and 15 mg of pioglitazone once daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors.