Pioglitazone

Monotherapy and Combination Therapy Pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings [see Clinical Studies (14) ] . Important Limitations of Use Pioglitazone tablets exert its antihyperglycemic effect only in the presence of endogenous insulin. Pioglitazone tablets 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 ] . …

• Initiate pioglitazone tablets at 15 mg or 30 mg once daily
• Limit initial dose to 15 mg once daily in patients with NYHA Class I or II heart failure. • If there is inadequate glycemic control, the dose can be increased in 15 mg increments up to a maximum of 45 mg once daily. • Obtain liver tests before starting pioglitazone tablets
• If abnormal, use caution when treating with pioglitazone tablets, investigate the probable cause, treat (if possible) and follow appropriately
• Monitoring liver tests while on pioglitazone tablets are not recommended in patients without liver disease
• Recommendations for All Patients Pioglitazone tablets should be taken once daily and can be taken without regard to meals
• The recommended starting dose for patients without congestive heart failure is 15 mg or 30 mg once daily
• The recommended starting dose for patients with congestive heart failure (NYHA Class I or II) is 15 mg once daily
• The dose can be titrated in increments of 15 mg up to a maximum of 45 mg once daily based on glycemic response as determined by HbA1c
• After initiation of pioglitazone tablets 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 and ]
• Liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) should be obtained prior to initiating pioglitazone tablets. …

• 15 mg are white to off-white, round, biconvex, uncoated tablets, debossed with “31” on one side and “H” on other side. • 30 mg are white to off-white, round, flat faced, beveled edge uncoated tablets, debossed with “32” on one side and “H” on other side. • 45 mg are white to off-white, round, flat faced, beveled edge uncoated tablets, debossed with “33” on one side and “H” on other side. …

• Safety and effectiveness of pioglitazone
• In pediatric patients have not been established
• Pioglitazone is not recommended for use
• In pediatric patients based on adverse effects observed
• In adults, including fluid retention and congestive heart failure, fractures, and urinary bladder tumors [see ]

A total of 92 patients (15.2%) treated with pioglitazone in the three pooled 16- to 26-week double-blind, placebo-controlled, monotherapy trials were ≥65 years old and two patients (0.3%) were ≥75 years old. In the two pooled 16- to 24-week add-on to sulfonylurea trials, 201 patients (18.7%) treated with pioglitazone were ≥ 65 years old and 19 (1.8%) were ≥ 75 years old. …

• See FDA-Approved Patient Labeling (Medication Guide). • It is important to instruct patients to adhere to dietary instructions and to have blood glucose and glycosylated hemoglobin tested regularly
• During periods of stress such as fever, trauma, infection, or surgery, medication requirements may change and patients should be reminded to seek medical advice promptly. • Patients who experience an unusually rapid increase in weight or edema or who develop shortness of breath or other symptoms of heart failure while on pioglitazone should immediately report these symptoms to a physician. …

• Initiation in patients with established NYHA Class III or IV heart failure [see ]. • Use in patients with known hypersensitivity to pioglitazone or any other component of pioglitazone tablets. • Initiation in patients with established New York Heart Association (NYHA) Class III or IV heart failure [see ] . • Use in patients with known hypersensitivity to pioglitazone or any other component of pioglitazone tablets.

• Strong CYP2C8 inhibitors (e.g., gemfibrozil) increase pioglitazone concentrations. Limit pioglitazone dose to 15 mg daily. , • CYP2C8 inducers (e.g., rifampin) may decrease pioglitazone concentrations. • Topiramate may decrease pioglitazone concentrations. 7.1 Strong CYP2C8 Inhibitors An inhibitor of CYP2C8 (e.g., gemfibrozil) significantly increases the exposure (area under the serum concentration-time curve or AUC) and half-life (t 1/2 ) of pioglitazone. Therefore, the maximum recommended dose of pioglitazone is 15 mg daily if used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see and ]. …

• Congestive heart failure: Fluid retention may occur and can exacerbate or lead to congestive heart failure. Combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk. Monitor patients for signs and symptoms. • Hypoglycemia: When used with insulin or an insulin secretagogue, a lower dose of the insulin or insulin secretagogue may be needed to reduce the risk of hypoglycemia. • Hepatic effects: Postmarketing reports of hepatic failure, sometimes fatal. Causality cannot be excluded. If liver injury is detected, promptly interrupt pioglitazone and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. …

The following serious adverse reactions are discussed elsewhere in the labeling: • Congestive heart failure [see and ] • Edema [see Warnings and Precautions ] • Fractures [see Warnings and Precautions ] Most common adverse reactions (≥5%) are upper respiratory tract infection, headache, sinusitis, myalgia, and pharyngitis. To report SUSPECTED ADVERSE REACTIONS, contact Rising Health, LLC at 1-833-395-6928 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

8.1 Pregnancy Risk Summary Limited data with pioglitazone in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations] . …

During controlled clinical trials, one case of overdose with pioglitazone was reported. A male patient took 120 mg per day for four days, then 180 mg per day for seven days. The patient denied any clinical symptoms during this period. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms.

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.