圣路易斯(MD Consult)—2009年5月14日，武田制药公司(Takeda Pharmaceutical Company Limited)宣布，美国食品药品管理局(FDA)已批准复方缓释药Actoplus Met XR(匹格列酮和二甲双胍)用于治疗2型糖尿病。该药可辅助饮食和运动，共同治疗2型糖尿病。Actoplus Met XR适用于治疗曾接受过Actos (匹格列酮)和二甲双胍治疗的2型糖尿病成人患者或经Actos单药治疗或二甲双胍单药治疗后血糖控制不佳的2型糖尿病成人患者。
Actoplus Met XR中的Actos可直接针对胰岛素抵抗起作用。第2个成分——二甲双胍，可通过减少肝脏生成的葡萄糖量而发挥作用。
Actoplus Met XR治疗可引起或加重充血性心力衰竭。患者如果出现体重迅速增加、液体潴留或气短，则应与经治医生联系。此外，少数服用二甲双胍的患者会出现乳酸酸中毒。在约半数情况下，乳酸酸中毒具有致命性。由于乳酸酸中毒最常发生于有肾脏疾病的患者，因此不应为肾病患者或年龄≥80岁的肾功能损害患者开具Actoplus Met XR处方。另外，代谢性酸中毒患者或酗酒患者也不应服用Actoplus Met XR。严重感染患者和采用静脉注射造影剂进行放射学检查的患者不应停用Actoplus met XR。
患者应在接受Actoplus Met XR治疗前进行肝功能实验室检查，并在此后定期进行此类检查。Actoplus Met XR禁用于患有活动性肝病的患者。患者如果出现恶心、呕吐、腹痛、疲劳、食欲不振、皮肤发黄或尿色变暗，则应与经治医生联系。
武田制药公司预期Actopuls Met XR可在2009年底前上市。
Generic Name and Formulations:
Pioglitazone (as HCl), metformin HCl extended-release; 15mg/1000mg, 30mg/1000mg; tabs.

Company:
Takeda Pharmaceuticals North America, Inc.

Indications for ACTOPLUS MET XR:
Adjunct to diet and exercise to improve glycemic control in type 2 diabetes in patients already on pioglitazone and metformin, or when response to pioglitazone or metformin alone is inadequate.

Adult Dose for ACTOPLUS MET XR:
Swallow whole. Give once daily with the evening meal. Individualize. Previously on pioglitazone and/or metformin: switch on a mg/mg basis. Initially 15mg/1000mg or 30mg/1000mg once daily; may adjust after 8–12 weeks; max 45mg pioglitazone/2000mg metformin per day. Elderly, debilitated, malnourished: max doses not recommended.

Children's Dose for ACTOPLUS MET XR:
Not recommended.

See Also:
ACTOPLUS MET

Pharmacological Class:
Thiazolidinedione + biguanide.

Contraindications:
NYHA Class III or IV heart failure. Renal disease or dysfunction. Metabolic acidosis, ketoacidosis. Concomitant intravascular iodinated contrast agents (suspend during and for 48 hours after use).

Warnings/Precautions:
Not for treating type 1 diabetes. Symptomatic HF: not recommended. CHF: NYHA Class II: start at lowest approved dose and titrate carefully. Edema. May increase plasma volume (monitor for signs/symptoms of heart failure); discontinue if cardiac status deteriorates, or if lactic acidosis, shock, acute MI, sepsis, or hypoxemia occurs. Confirm normal renal function before starting and monitor (esp. in patients ≥80yrs). Avoid in hepatic disease. Do not start therapy in active liver disease or if ALT >2.5xULN. Monitor ALT at baseline, then periodically. If ALT 1–2.5xULN, follow-up and monitor closely; discontinue if ALT >3xULN persists or if jaundice occurs. Not for use in patients with history of troglitazone-associated jaundice. Suspend therapy if dehydration occurs or before surgery. Monitor blood (esp. serum Vit. B12 in susceptible patients). Stress. Elderly, debilitated, uncompensated strenuous exercise, malnourished or deficient caloric intake, adrenal or pituitary insufficiency, or alcohol intoxication: increased risk of hypoglycemia. Resumption of premenopausal ovulation in anovulatory patients may occur (may result in unintended pregnancy). Pregnancy (Cat.C; not recommended; consider using insulin instead). Nursing mothers: not recommended.

Interactions:
See Contraindications. Potentiated by CYP2C8 inhibitors (eg, gemfibrozil). Antagonized by CYP2C8 inducers (eg, rifampin). Antagonizes oral contraceptives, midazolam. Monitor for heart failure with insulin. Avoid excessive alcohol intake (potentiates effects of metformin on lactate). Cationic drugs eliminated by renal tubular secretion, furosemide, nifedipine: may increase metformin levels. Increased risk of hyperglycemia with diuretics, steroids, phenothiazines, phenytoin, sympathomimetics, calcium channel blockers, niacin, thyroid products, estrogens, oral contraceptives, isoniazid. β-blockers may mask hypoglycemia.

Adverse Reactions:
Upper respiratory tract infection, GI upset, edema, headache, urinary tract infection, dizziness, weight gain, lactic acidosis (rare, half the cases are fatal); also women: risk of fracture.

How Supplied:
Tabs—60, 180; XR tabs—30, 60, 90