Pioglitazone Hydrochloride And Metformin Hydrochloride Side Effects

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Congestive heart failure [see Boxed Warning , Warnings and Precautions (5.1) ] Lactic acidosis [see Boxed Warning , Warnings and Precautions (5.2) ] Edema [see Warnings and Precautions (5.3) ] Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues [see Warnings and Precautions (5.4) ] Hepatic Effects [see Warnings and Precautions (5.5) ] Urinary Bladder Tumors [see Warnings and Precautions (5.6) ] Fractures [see Warnings and Precautions (5.7) ] Macular Edema [see Warnings and Precautions (5.8) ] Vitamin B 12 Levels [see Warnings and Precautions (5.9) ] Most common adverse reactions (>5%) are upper respiratory tract infection, edema, diarrhea, headache and weight gain.

(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc.

at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Pioglitazone Over 8,500 patients with type 2 diabetes mellitus have been treated with pioglitazone in randomized, double-blind, controlled clinical trials, including 2,605 patients with type 2 diabetes mellitus and macrovascular disease treated with pioglitazone from the PROactive clinical trial.

In these trials, over 6,000 patients have been treated with pioglitazone for six months or longer, over 4,500 patients have been treated with pioglitazone for one year or longer, and over 3,000 patients have been treated with pioglitazone for at least two years.

In six pooled 16 to 26 week placebo-controlled monotherapy and 16 to 24 week add-on combination therapy trials, the incidence of withdrawals due to adverse events was 4.5% for patients treated with pioglitazone and 5.8% for comparator-treated patients.

The most common adverse events leading to withdrawal were related to inadequate glycemic control, although the incidence of these events was lower (1.5%) with pioglitazone than with placebo (3%).

In the PROactive trial, the incidence of withdrawals due to adverse events was 9% for patients treated with pioglitazone and 7.7% for placebo-treated patients.

Congestive heart failure was the most common serious adverse event leading to withdrawal occurring in 1.3% of patients treated with pioglitazone and 0.6% of patients treated with placebo.