INDICATIONS AND USAGE
ACTOPLUS MET XR is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both pioglitazone and metformin is appropriate [see Clinical Studies ].
Important Limitations of Use
Pioglitazone exerts its antihyperglycemic effect only in the presence of endogenous insulin. ACTOPLUS MET XR should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would not be effective in these settings.
Use caution in patients with liver disease [see Warnings and Precautions].
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DOSAGE AND ADMINISTRATION
Recommendations for All Patients
ACTOPLUS MET XR should be taken with meals to reduce the gastrointestinal side effects associated with metformin.
If therapy with a combination tablet containing pioglitazone and extended-release metformin is considered appropriate the recommended starting dose is:
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•15 mg/1000 mg or 30 mg/1000 mg once daily and gradually titrated as needed, after assessing adequacy of therapeutic response and tolerability,
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•for patients with NYHA Class I or Class II congestive heart failure: 15 mg/1000 mg or 30 mg/1000 mg once daily and gradually titrated as needed, after assessing adequacy of therapeutic response and tolerability.
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•for patients inadequately controlled on metformin monotherapy: 15 mg/1000 mg twice daily or 30 mg/1000 mg once daily (depending on the dose of metformin already being taken) and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability,
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•for patients inadequately controlled on pioglitazone monotherapy: 15 mg/1000 mg twice daily or 30 mg/1000 mg once daily and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability.
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•for patients who are changing from combination therapy of pioglitazone plus metformin as separate tablets: ACTOPLUS MET XR should be taken at doses that are as close as possible to the dose of pioglitazone and metformin already being taken.
ACTOPLUS MET XR may be titrated up to a maximum daily dose of 45 mg/2000 mg of pioglitazone/extended-release metformin.
Metformin doses above 2000 mg may be better tolerated given three times a day.
Patients should be informed that ACTOPLUS MET XR must be swallowed whole and not chewed, cut, or crushed, and that the inactive ingredients may occasionally be eliminated in the feces as a soft mass that may resemble the original tablet.
After initiation of ACTOPLUS MET XR or with dose increase, monitor patients carefully for adverse reactions related to fluid retention such as weight gain, edema, and signs and symptoms of congestive heart failure [see Boxed Warning and Warnings and Precautions ]. Liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) should be obtained prior to initiating ACTOPLUS MET XR. Routine periodic monitoring of liver tests during treatment with ACTOPLUS MET XR is not recommended in patients without liver disease. Patients who have liver test abnormalities prior to initiation of ACTOPLUS MET XR or who are found to have abnormal liver tests while taking ACTOPLUS MET XR should be managed as described under Warnings and Precautions [see Warnings and Precautions (5.5) and Clinical Pharmacology].
Concomitant Use with an Insulin Secretagogue or Insulin
If hypoglycemia occurs in a patient coadministered ACTOPLUS MET XR and an insulin secretagogue (e.g., sulfonylurea), the dose of the insulin secretagogue should be reduced.
If hypoglycemia occurs in a patient coadministered ACTOPLUS MET XR and insulin, the dose of insulin should be decreased by 10% to 25%. Further adjustments to the insulin dose should be individualized based on glycemic response.
Concomitant Use with Strong CYP2C8 Inhibitors
Coadministration of pioglitazone (one of the ingredients in ACTOPLUS MET XR) and gemfibrozil, a strong CYP2C8 inhibitor, increases pioglitazone exposure by approximately 3-fold. Therefore, the maximum recommended dose of ACTOPLUS MET XR is 15 mg/1000 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see Drug Interactions and Clinical Pharmacology].
DOSAGE FORMS AND STRENGTHS
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•15 mg/1000 mg tablets: White to off-white, round, film-coated tablets debossed with “4833X” on one side and “15/1000” on the other
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•30 mg/1000 mg tablets: White to off-white, oblong, film-coated tablets debossed with “4833X” on one side and “30/1000” on the other
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HOW SUPPLIED/STORAGE AND HANDLING
ACTOPLUS MET XR is available in 15 mg pioglitazone (as the base)/1000 mg metformin hydrochloride extended-release and 30 mg pioglitazone (as the base)/1000 mg metformin hydrochloride extended-release tablets as follows:
15 mg/1000 mg tablet: white to off-white, round, film-coated tablets debossed with “4833X” on one side and “15/1000” on the other, available in:
NDC 64764-510-30 Bottles of 30
NDC 64764-510-60 Bottles of 60
NDC 64764-510-90 Bottles of 90
30 mg/1000 mg tablet: white to off-white round, film-coated tablets debossed with “4833X” on one side and “30/1000” on the other, available in:
NDC 64764-310-30 Bottles of 30
NDC 64764-310-60 Bottles of 60
NDC 64764-310-90 Bottles of 90
Storage
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep container tightly closed, and protect from moisture and humidity.
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