WARNING: CONGESTIVE HEART FAILURE AND LACTIC ACIDOSIS
Congestive Heart Failure
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Thiazolidinediones, including pioglitazone, which is a component of ACTOPLUS MET XR, cause or exacerbate congestive heart failure in some patients [see Warnings and Precautions ].
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After initiation of ACTOPLUS MET XR, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of ACTOPLUS MET XR must be considered [see Warnings and Precautions].
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ACTOPLUS MET XR is not recommended in patients with symptomatic heart failure.
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Initiation of ACTOPLUS MET XR in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated [see Contraindications (4) and Warnings and Precautions ].
Lactic Acidosis
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Lactic acidosis is a rare, but serious complication that can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure [see Warnings and Precautions].
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The onset is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate [see Warnings and Precautions ].
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If acidosis is suspected, ACTOPLUS MET XR should be discontinued and the patient hospitalized immediately [see Warnings and Precautions].
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SUMMARY
ACTOPLUS MET® tablets are formulated with pioglitazone hydrochloride and immediate-release metformin hydrochloride. ACTOPLUS MET® XR tablets are formulated with pioglitazone hydrochloride and extended-release metformin hydrochloride. Both ACTOPLUS MET® and ACTOPLUS MET® XR contain two oral antihyperglycemic drugs used in the management of type 2 diabetes: pioglitazone and metformin.
ACTOPLUS MET and ACTOPLUS MET XR are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with pioglitazone and metformin or who have inadequate glycemic control on pioglitazone alone or metformin alone.
Management of type 2 diabetes should also include nutritional counseling, weight reduction as needed, and exercise. These efforts are important not only in the primary treatment of type 2 diabetes, but also to maintain the efficacy of drug therapy. Prior to initiation or escalation of oral antidiabetic therapy in patients with type 2 diabetes mellitus, secondary causes of poor glycemic control, e.g., infection, should be investigated and treated.
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NEWS HIGHLIGHTS
Published Studies Related to Actoplus Met XR (Pioglitazone / Metformin)
PIOfix-study: effects of pioglitazone/metformin fixed combination in comparison with a combination of metformin with glimepiride on diabetic dyslipidemia. [2011.06]
CONCLUSIONS: With comparable glycemic control, the fixed PM combination was more efficacious on HDL cholesterol improvement than the GM combination. Additional positive effects were observed for biomarkers of lipid metabolism, beta-cell function, activity of the visceral adipose tissue, and chronic systemic inflammation.
Effects of pioglitazone and metformin fixed-dose combination therapy on cardiovascular risk markers of inflammation and lipid profile compared with pioglitazone and metformin monotherapy in patients with type 2 diabetes. [2010.12]
. Type 2 diabetes mellitus (T2DM) treatment should not increase cardiovascular (CV) risk and at best could provide benefit beyond lowering glucose... Thus, treatment with the FDC resulted in improved levels of CV biomarkers, which were better than or equal to monotherapy.
Efficacy and safety of pioglitazone/metformin fixed-dose combination therapy compared with pioglitazone and metformin monotherapy in treating patients with T2DM. [2009.12]
BACKGROUND: Studies have shown that many patients with type 2 diabetes do not achieve optimal glycemic control, and progression of diabetes over time requires more than one pharmacotherapy to achieve glycemic goal. OBJECTIVE: To examine the efficacy and safety of the fixed-dose combination (FDC) of pioglitazone 15 mg and metformin 850 mg versus its individual components in a twice-daily regimen over 24 weeks of treatment in type 2 diabetes patients who were currently not receiving antidiabetes therapy... CONCLUSIONS: Overall, treatment with pioglitazone/metformin FDC demonstrated greater efficacy than its individual components. The FDC therapy was well tolerated, with reduced or similar adverse event rates compared with each individual monotherapy.
Effects of pioglitazone and metformin fixed-dose combination therapy on
cardiovascular risk markers of inflammation and lipid profile compared with
pioglitazone and metformin monotherapy in patients with type 2 diabetes. [2010]
. Type 2 diabetes mellitus (T2DM) treatment should not increase cardiovascular
(CV) risk and at best could provide benefit beyond lowering glucose... Thus, treatment with the FDC resulted in improved levels of CV biomarkers,
which were better than or equal to monotherapy.
Combined pioglitazone and metformin treatment maintains the beneficial effect of short-term insulin infusion in patients with type 2 diabetes: results from a pilot study. [2009.11.01]
BACKGROUND: The aim of our study was to examine the efficacy of short-term intravenous insulin intervention followed by oral pioglitazone/metformin therapy to prevent patients from continuous insulin application... CONCLUSIONS: Our pilot study demonstrated that a beneficial effect of a short-term intravenous insulin application on glycemic control was effectively maintained by pioglitazone/metformin treatment for at least 4 months. In addition, the oral therapy significantly improved cardiovascular risk parameters.
Clinical Trials Related to Actoplus Met XR (Pioglitazone / Metformin)
Bioequivalence Study of Torrent Pharmaceuticals Ltd's Pioglitazone Hydrochloride and Metformin Hydrochloride Tablets Under Fed Conditions [Completed]
Objective:
subjects to compare the single dose bioavailability of Torrent's Pioglitazone Hydrochloride
and Metformin Hydrochloride Tablets 15 mg/850 mg and Actoplus Met® (pioglitazone
hydrochloride and metformin hydrochloride) Tablets 15 mg/850 mg of Takeda Pharmaceuticals
America, Inc. USA. Dosing periods of studies were separated by a washout period of 14 days.
Study Design:
Randomized, Two-Way Crossover, Single-Dose, and Open-Label
Bioequivalence Study of Torrent Pharmaceuticals Ltd's Pioglitazone Hydrochloride and Metformin Hydrochloride Tablets Under Fasting Conditions [Completed]
Objective:
subjects to compare the single dose bioavailability of Torrent's Pioglitazone Hydrochloride
and Metformin Hydrochloride Tablets 15 mg/850 mg and Actoplus Met® (pioglitazone
hydrochloride and metformin hydrochloride) Tablets 15 mg/850 mg of Takeda Pharmaceuticals
America, Inc. USA. Dosing periods of studies were separated by a washout period of 14 days.
Study Design:
Randomized, Two-Way Crossover, Single-Dose, and Open-Label
Efficacy and Safety of Pioglitazone and Metformin Combination Therapy in Treating Type 2 Diabetes Mellitus. [Completed]
The purpose of this study is to determine the efficacy of pioglitazone, twice daily (BID),
combined with metformin versus pioglitazone taken alone and metformin taken alone in
treating Type 2 Diabetes Mellitus.
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Page last updated: 2013-02-10
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