ACTOPLUS MET XR Rx
Generic Name and Formulations:
Pioglitazone (as HCl), metformin HCl extended-release; 15mg/1000mg, 30mg/1000mg; tabs.
Takeda Pharmaceutical Company
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.
Limitations Of use:
Not for treating type 1 diabetes.
Swallow whole. Give once daily with the evening meal. Individualize. Previously on pioglitazone and/or metformin: switch on a mg/mg basis. With or without CHF (NYHA Class I or II): initially 15mg/1000mg or 30mg/1000mg once daily; may titrate gradually as needed. Inadequately controlled on metformin or pioglitazone monotherapy: 15mg/1000mg twice daily or 30mg/1000mg once daily; may titrate gradually as needed. All: max 45mg pioglitazone/2000mg metformin per day. Concomitant strong CYP2C8 inhibitors: max 15mg/1000mg daily. Renal impairment (eGFR 30–45mL/min/1.73m2): not recommended. If eGFR <45mL/min/1.73m2, assess risk/benefit; discontinue if eGFR <30mL/min/1.73m2.
NYHA Class III or IV heart failure. Severe renal impairment (eGFR <30mL/min/1.73m2). Metabolic acidosis. Diabetic ketoacidosis.
Congestive heart failure. Lactic acidosis.
Symptomatic HF: not recommended. Monitor for signs/symptoms of CHF; discontinue or reduce dose if occurs. Increased risk of metformin-associated lactic acidosis in renal or hepatic impairment, concomitant use of certain drugs (eg, cationic drugs), ≥65yrs of age, undergoing radiological contrast study, surgery and other procedures, hypoxic states, and excessive alcohol intake; discontinue if lactic acidosis occurs. Discontinue at time of, or prior to intravascular iodinated contrast imaging in patients with eGFR 30–60mL/min/1.73m2, history of hepatic impairment, alcoholism, heart failure, or will be given intra-arterial contrast; reevaluate eGFR 48hrs after procedure and restart therapy if renally stable. Suspend therapy if dehydration occurs or before surgery. Avoid if clinical or lab evidence of hepatic disease. Assess renal function prior to starting and periodically thereafter; more frequently in elderly or if eGFR <60mL/min/1.73m2. Obtain LFTs before initiating therapy; if abnormalities detected, interrupt and assess probable cause; do not restart if ALT >3XULN with total bilirubin >2XULN. Active bladder cancer: not recommended. Prior history of bladder cancer: consider glycemic control benefits vs. risk of cancer recurrence. Risk of fractures (esp. females). Perform regular eye exams. 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. Nursing mothers.
Thiazolidinedione + biguanide.
See Contraindications. Potentiated by CYP2C8 inhibitors (eg, gemfibrozil). Antagonized by CYP2C8 inducers (eg, rifampin) or topiramate (monitor for adequate glycemic control). Antagonizes oral contraceptives, midazolam. Monitor for heart failure with insulin. Avoid excessive alcohol intake (potentiates effects of metformin on lactate). Increased risk of lactic acidosis with topiramate, other carbonic anhydrase inhibitors (eg, zonisamide, acetazolamide, dichlorphenamide); monitor. Concomitant cationic drugs that interfere with renal tubular transport systems (eg, ranolazine, vandetanib, dolutegravir, cimetidine) may increase metformin levels. Increased risk of hyperglycemia with diuretics, steroids, phenothiazines, phenytoin, sympathomimetics, calcium channel blockers, niacin, thyroid products, estrogens, oral contraceptives, isoniazid. May need lower dose of concomitant sulfonylurea or insulin to reduce risk of hypoglycemia. β-blockers may mask hypoglycemia.
Upper respiratory tract infection, edema, diarrhea, headache, weight gain, lactic acidosis (rare, half the cases are fatal), macular edema.
Tabs—60, 180; XR tabs—30, 60, 90