Metformindosage

Obtain liver tests before initiation. If abnormal, use caution when treating with pioglitazone and metformin hydrochloride, investigate the probable cause, treat (if possible), and follow appropriately. Take orally with meals to reduce gastrointestinal adverse reactions with metformin Individualize the starting dose based on the patient’s current regimen and titrate the dosage gradually, as needed after assessing therapeutic response and tolerability. The maximum recommended total daily dosage is pioglitazone 45 mg and metformin 2,550 mg. Recommended starting dosage in patients with NYHA Class I or Class II congestive heart failure is 15 mg of pioglitazone and 500 mg of metformin hydrochloride or 15 mg of pioglitazone and 850 mg of metformin hydrochloride orally once daily. Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR). Contraindicated in patients with eGFR below 30 mL/min Initiation is not recommended in patients with eGFR between 30 to 45 mL/min Assess risk/benefit of continuing pioglitazone and metformin hydrochloride if eGFR falls below 45 mL/min Discontinue if eGFR falls below 30 mL/min Monitor patients for adverse events related to fluid retention after initiation and dose increases. Pioglitazone and metformin hydrochloride may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures.

2.1 Important

Dosage and Administration Information Obtain liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) prior to initiating pioglitazone and metformin hydrochloride tablets. Pioglitazone and metformin hydrochloride tablet contains 15 mg of pioglitazone and 500 mg of metformin hydrochloride or 15 mg of pioglitazone and 850 mg of metformin hydrochloride in each tablet. Take pioglitazone and metformin hydrochloride tablets with meals to reduce gastrointestinal adverse reactions with metformin. 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 pioglitazone and metformin hydrochloride tablets based on the patient's current regimen and the available strength of pioglitazone and metformin hydrochloride tablets (see Table 1).

Table 1: Recommended Starting Dosage Based on the Patient’s Current Regimen *For dosage recommendations for patients with renal impairment and/or congestive heart failure, see Dosage and Administration Current Regimen Starting Dosage of Pioglitazone and Metformin Hydrochloride tablets (15 mg of pioglitazone and 850 mg of metformin hydrochloride per tablet)* Not treated with either pioglitazone or metformin hydrochloride One tablet orally once daily Metformin hydrochloride One tablet orally once or twice daily. Select a dosage that is as close as possible to the current dosage of metformin hydrochloride Pioglitazone One tablet orally once daily Pioglitazone and metformin hydrochloride Select a dosage that is as close as possible to the current dosage of pioglitazone and metformin hydrochloride while not exceeding three tablets orally per day. Dosage Titration for Additional Glycemic Control Titrate the pioglitazone and metformin hydrochloride tablets dosage gradually, as needed, after assessing therapeutic response and tolerability. Pioglitazone and metformin hydrochloride tablets 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 hydrochloride). Total daily dosages of 2,550 mg of metformin hydrochloride may be taken in divided doses three times a day to reduce gastrointestinal adverse reactions.

2.3 Recommendations for

Use in Patients with Renal Impairment Assess renal function prior to initiation of pioglitazone and metformin hydrochloride tablets and periodically thereafter. Pioglitazone and metformin hydrochloride tablets are contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min. Initiation of pioglitazone and metformin hydrochloride tablets in patients with an eGFR between 30 to 45 mL/min is not recommended. In patients taking pioglitazone and metformin hydrochloride tablets whose eGFR later falls below 45 mL/min, assess the benefit and risk of continuing therapy. Discontinue pioglitazone and metformin hydrochloride tablets if the patient's eGFR later falls below 30 mL/min.

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 pioglitazone and metformin hydrochloride tablets are 15 mg of pioglitazone and 500 mg of metformin or 15 mg of pioglitazone and 850 mg of metformin. Monitoring for Fluid Retention and Dosage Modifications for Congestive Heart Failure After initiation of pioglitazone and metformin hydrochloride tablets 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 pioglitazone and metformin hydrochloride tablets, consider discontinuation of pioglitazone and metformin hydrochloride tablets or dosage reduction of pioglitazone in pioglitazone and metformin hydrochloride tablets.

2.5 Coadministration with

Strong CYP2C8 Inhibitors The maximum recommended dosage of pioglitazone and metformin hydrochloride tablets is one tablet (15 mg of pioglitazone and 850 mg of metformin hydrochloride) once daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors.

2.6 Discontinuation for

Iodinated Contrast Imaging Procedures Discontinue pioglitazone and metformin hydrochloride tablets 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 pioglitazone and metformin hydrochloride tablets if renal function is stable.