糖尿病 (TZD / DPP4I) Type 2 diabetes mellitus

The fixed-dose combination product of alogliptin benzoate and pioglitazone hydrochloride combines 2 antihyperglycemic agents which act differently to achieve glycemic control in patients with type 2 diabetes. Alogliptin benzoate is a dipeptidyl peptidase-4 (DPP-4) inhibitor that reduces fasting and postprandial glucose concentrations in a glucose-dependent manner by slowing the inactivation of incretin hormones (eg, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)) by binding to and inhibiting the DPP-4 enzyme. Pioglitazone hydrochloride, a member of the thiazolidinedione class, works as an insulin-sensitizing agent to improve peripheral glucose utilization

Absorption:
Alogliptin,Bioavailability: approximately 100%
Distribution:
Alogliptin, Vd: 417 L ;Pioglitazone, Vd: 0.63 +/- 0.41 L/kg
Metabolism:
Alogliptin, Liver: limited, via CYP2D6 and CYP3A4
Pioglitazone, Liver, extensive, hydroxylation and oxidation via CYP2C8 and to a lesser degree, CYP3A4, substrate of CYP2C8,weak CYP3A4 inducer.
Elimination Half Life:Alogliptin, 21 hours;Pioglitazone, 3 to 7 hours

hypersensitivity to alogliptin, pioglitazone, or to any component of the product
NYHA Class III or IV heart failure

C(FDA)

Infant risk cannot be ruled out.(MDX)

Common:
Endocrine metabolic: Hypoglycemia
Musculoskeletal: Backache (4.2% )
Respiratory: Nasopharyngitis (4.9%), Respiratory tract infection (4.1% )
Serious:
Cardiovascular: Congestive heart failure
Dermatologic: Stevens-Johnson syndrome
Gastrointestinal: Pancreatitis (Alogliptin, 0.2% )
Hepatic: Liver failure
Immunologic: Anaphylaxis, Hypersensitivity reaction (alogliptin, 0.6% )
Musculoskeletal: Arthralgia, Fracture of bone (pioglitazone, 5.1% (women) )
Ophthalmic: Diabetic macular edema
Renal: Bladder cancer (Pioglitazone (patients with macrovascular disease), 0.23% to 0.54% )

Type 2 diabetes mellitus:
Initial, alogliptin 25 mg/pioglitazone 15 mg OR alogliptin 25 mg/pioglitazone 30 mg orally once daily
(Previously receiving pioglitazone) Alogliptin 25 mg/pioglitazone 15 mg OR alogliptin 25 mg/pioglitazone 30 mg OR alogliptin 25 mg/pioglitazone 45 mg orally once daily; initial dose based on current therapy
(Switching from alogliptin coadministered with pioglitazone) Initial dose based on current therapy
Maintenance, dose orally once daily based on glycemic response (HbA1c); MAX: alogliptin 25 mg/pioglitazone 45 mg orally once daily
concomitant use with strong CYP2C8 inhibitors: maximum dose, alogliptin 25 mg/pioglitazone 15 mg ORALLY once daily
congestive heart failure (NYHA class I or II): initial dose, alogliptin 25 mg/pioglitazone 15 mg ORALLY once daily
congestive heart failure (NYHA class III or IV): use contraindicated

General Dosage Information: safety and efficacy not established in pediatric patients

renal impairment, mild (CrCl 60 mL/min or greater): no dose adjustment necessary
renal impairment, moderate (CrCl 30 mL/min to less than 60 mL/min): alogliptin 12.5 mg/pioglitazone 15 mg OR alogliptin 12.5 mg/pioglitazone 30 mg OR alogliptin 12.5 mg/pioglitazone 45 mg ORALLY once daily
renal impairment, severe or ESRD: use not recommended

hepatic impairment, use caution; if liver injury occurs, interrupt therapy and assess for cause; do not restart therapy if cause is not identified