Actoplus Met Dosage

2.1 Important Dosage and Administration Information

• Obtain liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) prior to initiating ACTOPLUS MET [see Warnings and Precautions (5.5)].
• ACTOPLUS MET contains 15 mg of pioglitazone and 850 mg of metformin hydrochloride (HCl) in each tablet.
• Take ACTOPLUS MET with meals to reduce gastrointestinal adverse reactions with metformin [see Adverse Reactions (6.1)].
• If a dose is missed, do not double the next dose.

2.2 Recommended Dosage and Administration

Recommended Starting Dosage Based on Current Regimen

Individualize the starting dosage of ACTOPLUS MET based on the patient's current regimen and the available strength of ACTOPLUS MET (see Table 1).

Dosage Titration for Additional Glycemic Control

Titrate the ACTOPLUS MET dosage gradually, as needed, after assessing therapeutic response and tolerability.

ACTOPLUS MET may be increased to a maximum recommended total daily dosage of three tablets per day (45 mg of pioglitazone and 2,550 mg of metformin HCl). Total daily dosages of 2,550 mg of metformin HCl may be taken in divided doses three times a day to reduce gastrointestinal adverse reactions [see Adverse Reactions (6.1)].

2.3 Recommendations for Use in Patients with Renal Impairment

• Assess renal function prior to initiation of ACTOPLUS MET and periodically thereafter [see Use in Specific Populations (8.6)].
• ACTOPLUS MET is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min.
• Initiation of ACTOPLUS MET in patients with an eGFR between 30 to 45 mL/min is not recommended.
• In patients taking ACTOPLUS MET whose eGFR later falls below 45 mL/min, assess the benefit and risk of continuing therapy.
• Discontinue ACTOPLUS MET if the patient’s eGFR later falls below 30 mL/min [see Contraindications (4), Warnings and Precautions (5.2)].

2.4 Recommendations for Congestive Heart Failure

Starting Dosage in Patients with NYHA Class I or II Congestive Heart Failure

For patients with preexisting NYHA Class I or II congestive heart failure, the recommended starting dosage of ACTOPLUS MET is 15 mg of pioglitazone and 850 mg of metformin [see Boxed Warning and Warnings and Precautions (5.1)].

Monitoring for Fluid Retention and Dosage Modifications for Congestive Heart Failure

After initiation of ACTOPLUS MET or with dosage increase, monitor patients carefully for adverse reactions related to fluid retention as has been seen with pioglitazone (e.g., weight gain, edema and signs and symptoms of congestive heart failure).

If congestive heart failure develops while taking ACTOPLUS MET, consider discontinuation of ACTOPLUS MET or dosage reduction of pioglitazone in ACTOPLUS MET [see Boxed Warning and Warnings and Precautions (5.1)].

2.5 Coadministration with Strong CYP2C8 Inhibitors

The maximum recommended dosage of ACTOPLUS MET is one tablet (15 mg of pioglitazone and 850 mg of metformin HCl) once daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

Discontinuation for Iodinated Contrast Imaging Procedures

Discontinue ACTOPLUS MET at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart ACTOPLUS MET if renal function is stable [see Warnings and Precautions (5.2)].