PIOGLITAZONE HYDROCHLORIDE tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

PIOGLITAZONE HYDROCHLORIDE (UNII: JQT35NPK6C) (PIOGLITAZONE - UNII:X4OV71U42S)

Available from:

DirectRx

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

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 tablet exerts 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 WARNINGS AND PRECAUTIONS (5.3)] . Initiation in patients with established NYHA Class III or IV heart failure [see BOXED WARNING]. Use in patients with known hypersensitivity to pioglitazone or any other component of pioglitazone tablets. 8.1 Pregnancy Risk Summary Limited data with pioglitazone hydrochloride 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 a

Product summary:

14.1 Monotherapy Three randomized, double-blind, placebo-controlled trials with durations from 16 to 26 weeks were conducted to evaluate the use of pioglitazone hydrochloride as monotherapy in patients with type 2 diabetes. These trials examined pioglitazone hydrochloride at doses up to 45 mg or placebo once daily in a total of 865 patients. In a 26-week dose-ranging monotherapy trial, 408 patients with type 2 diabetes were randomized to receive 7.5 mg, 15 mg, 30 mg, or 45 mg of pioglitazone hydrochloride, or placebo once daily. Therapy with any previous antidiabetic agent was discontinued eight weeks prior to the double-blind period. Treatment with 15 mg, 30 mg, and 45 mg of pioglitazone hydrochloride produced statistically significant improvements in HbA1c and fasting plasma glucose (FPG) at endpoint compared to placebo (see FIGURE 1, TABLE 17). Figure 1 shows the time course for changes in HbA1c in this 26-week study. Figure 1. Mean Change from Baseline for HbA1c in a 26-Week Placebo-Controlled Dose-Ranging Study (Observed Values) Figure 1 Table 17. Glycemic Parameters in a 26-Week Placebo-Controlled Dose-Ranging Monotherapy Trial Placebo Pioglitazone Hydrochloride 15 mg Once Daily Pioglitazone Hydrochloride 30 mg Once Daily Pioglitazone Hydrochloride 45 mg Once Daily *Adjusted for baseline, pooled center, and pooled center by treatment interaction†p ≤ 0.05 vs. placebo Total Population HbA1c (%) N=79 N=79 N=85 N=76 Baseline (mean) 10.4 10.2 10.2 10.3 Change from baseline (adjusted mean *) 0.7 -0.3 -0.3 -0.9 Difference from placebo (adjusted mean *) 95% Confidence Interval -1.0 † (-1.6, -0.4) -1.0 † (-1.6, -0.4) -1.6 † (-2.2, -1.0) Fasting Plasma Glucose (mg/dL) N=79 N=79 N=84 N=77 Baseline (mean) 268 267 269 276 Change from baseline (adjusted mean *) 9 -30 -32 -56 Difference from placebo (adjusted mean *) 95% Confidence Interval -39 † (-63, -16) -41 † (-64, -18) -65 † (-89, -42) In a 24-week placebo-controlled monotherapy trial, 260 patients with type 2 diabetes were randomized to one of two forced-titration pioglitazone hydrochloride treatment groups or a mock-titration placebo group. Therapy with any previous antidiabetic agent was discontinued six weeks prior to the double-blind period. In one pioglitazone hydrochloride treatment group, patients received an initial dose of 7.5 mg once daily. After four weeks, the dose was increased to 15 mg once daily and after another four weeks, the dose was increased to 30 mg once daily for the remainder of the trial (16 weeks). In the second pioglitazone hydrochloride treatment group, patients received an initial dose of 15 mg once daily and were titrated to 30 mg once daily and 45 mg once daily in a similar manner. Treatment with pioglitazone hydrochloride, as described, produced statistically significant improvements in HbA1c and FPG at endpoint compared to placebo ( see TABLE 18 ) Table 18. Glycemic Parameters in a 24-Week Placebo-Controlled Forced-Titration Monotherapy Trial Placebo Pioglitazone Hydrochloride 30 mg * Once Daily Pioglitazone Hydrochloride 45 mg * Once Daily *Final dose in forced titration†Adjusted for baseline, pooled center, and pooled center by treatment interaction‡p ≤ 0.05 vs. placebo Total Population HbA1c (%) N=83 N=85 N=85 Baseline (mean) 10.8 10.3 10.8 Change from baseline (adjusted mean †) 0.9 -0.6 -0.6 Difference from placebo (adjusted mean †) 95% Confidence Interval -1.5 ‡ (-2.0, -1.0) -1.5 ‡ (-2.0, -1.0) Fasting Plasma Glucose (mg/dL) N=78 N=82 N=85 Baseline (mean) 279 268 281 Change from baseline (adjusted mean †) 18 -44 -50 Difference from placebo (adjusted mean †) 95% Confidence Interval -62 † (-82, 0.41) -68 † (-88, 0.48) In a 16-week monotherapy trial, 197 patients with type 2 diabetes were randomized to treatment with 30 mg of pioglitazone hydrochloride or placebo once daily. Therapy with any previous antidiabetic agent was discontinued six weeks prior to the double-blind period. Treatment with 30 mg of pioglitazone hydrochloride produced statistically significant improvements in HbA1c and FPG at endpoint compared to placebo ( see TABLE 19). Table 19. Glycemic Parameters in a 16-Week Placebo-Controlled Monotherapy Trial Placebo Pioglitazone Hydrochloride 30 mg Once Daily *Adjusted for baseline, pooled center, and pooled center by treatment interaction†p ≤ 0.050 vs. placebo Total Population HbA1c (%) N=93 N=100 Baseline (mean) 10.3 10.5 Change from baseline (adjusted mean *) 0.8 -0.6 Difference from placebo (adjusted mean *) 95% Confidence Interval -1.4 † (-1.8, -0.9) Fasting Plasma Glucose (mg/dL) N=91 N=99 Baseline (mean) 270 273 Change from baseline (adjusted mean *) 8 -50 Difference from placebo (adjusted mean *) 95% Confidence Interval -58 † (-77, -38) 14.2 Combination Therapy Three 16-week, randomized, double-blind, placebo-controlled clinical trials were conducted to evaluate the effects of pioglitazone hydrochloride (15 mg and/or 30 mg) on glycemic control in patients with type 2 diabetes who were inadequately controlled (HbA1c ≥8%) despite current therapy with a sulfonylurea, metformin, or insulin. In addition, three 24-week randomized, double-blind clinical trials were conducted to evaluate the effects of pioglitazone hydrochloride 30 mg vs. pioglitazone hydrochloride 45 mg on glycemic control in patients with type 2 diabetes who were inadequately controlled (HbA1c ≥8%) despite current therapy with a sulfonylurea, metformin, or insulin. Previous diabetes treatment may have been monotherapy or combination therapy. Add-on to Sulfonylurea Trials Two clinical trials were conducted with pioglitazone hydrochloride in combination with a sulfonylurea. Both studies included patients with type 2 diabetes on any dose of a sulfonylurea, either alone or in combination with another antidiabetic agent. All other antidiabetic agents were withdrawn at least three weeks prior to starting study treatment. In the first study, 560 patients were randomized to receive 15 mg or 30 mg of pioglitazone hydrochloride or placebo once daily for 16 weeks in addition to their current sulfonylurea regimen. Treatment with pioglitazone hydrochloride as add-on to sulfonylurea produced statistically significant improvements in HbA1c and FPG at endpoint compared to placebo add-on to sulfonylurea ( see TABLE 20) . Table 20. Glycemic Parameters in a 16-Week Placebo-Controlled, Add-on to Sulfonylurea Trial Placebo + Sulfonylurea Pioglitazone Hydrochloride 15 mg + Sulfonylurea Pioglitazone Hydrochloride 30 mg + Sulfonylurea *Adjusted for baseline, pooled center, and pooled center by treatment interaction†p ≤ 0.05 vs. placebo + sulfonylurea Total Population HbA1c (%) N=181 N=176 N=182 Baseline (mean) 9.9 10.0 9.9 Change from baseline (adjusted mean *) 0.1 -0.8 -1.2 Difference from placebo + sulfonylurea (adjusted mean *) 95% Confidence Interval -0.9 † (-1.2, -0.6) -1.3 † (-1.6, -1.0) Fasting Plasma Glucose (mg/dL) N=182 N=179 N=186 Baseline (mean) 236 247 239 Change from baseline (adjusted mean *) 6 -34 -52 Difference from placebo + sulfonylurea (adjusted mean *) 95% Confidence Interval -39 † (-52, -27) -58 † (-70, -46) In the second trial, 702 patients were randomized to receive 30 mg or 45 mg of pioglitazone hydrochloride once daily for 24 weeks in addition to their current sulfonylurea regimen. The mean reduction from baseline at Week 24 in HbA1 c was 1.6% for the 30 mg dose and 1.7% for the 45 mg dose (see Table 21). The mean reduction from baseline at Week 24 in FPG was 52 mg/dL for the 30 mg dose and 56 mg/dL for the 45 mg dose. The therapeutic effect of pioglitazone hydrochloride in combination with sulfonylurea was observed in patients regardless of the sulfonylurea dose. Table 21. Glycemic Parameters in a 24-Week Add-on to Sulfonylurea Trial Pioglitazone Hydroc

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

PIOGLITAZONE HYDROCHLORIDE- pioglitazone hydrochloride tablet
DirectRx
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MEDICATION GUIDE
Pioglitazone Tablets
(PYE o GLIT a zone)
Read this Medication Guide carefully before you start taking
pioglitazone tablets and each time you get a
refill. There may be new information. This information does not take
the place of talking with your doctor
about your medical condition or your treatment. If you have any
questions about pioglitazone tablets, ask
your doctor or pharmacist.
What is the most important information I should know about
pioglitazone tablets?
Pioglitazone tablets can cause serious side effects, including new or
worse heart failure.
Pioglitazone tablets can cause your body to keep extra fluid (fluid
retention), which leads to swelling (edema)
and weight gain. Extra body fluid can make some heart problems worse
or lead to heart failure. Heart failure
means your heart does not pump blood well enough
Do not take pioglitazone tablets if you have severe heart failure
If you have heart failure with symptoms (such as shortness of breath
or swelling), even if these symptoms are
not severe, pioglitazone tablets may not be right for you
Call your doctor right away if you have any of the following:
swelling or fluid retention, especially in the ankles or legs
shortness of breath or trouble breathing, especially when you lie down
an unusually fast increase in weight
unusual tiredness
Pioglitazone tablets can have other serious side effects. See " WHAT
ARE THE POSSIBLE SIDE EFFECTS
OF PIOGLITAZONE TABLETS?"
What are pioglitazone tablets?
Pioglitazone tablets are a prescription medicine used with diet and
exercise to improve blood sugar (glucose)
control in adults with type 2 diabetes. Pioglitazone tablets are a
diabetes medicine called pioglitazone that
may be taken alone or with other diabetes medicines.
It is not known if pioglitazone tablets are safe and effective in
children under the age of 18. Pioglitazone
tablets are not recommended for use in children.
Pioglitazone tablets are not for people with type

Summary of Product characteristics

PIOGLITAZONE HYDROCHLORIDE- PIOGLITAZONE HYDROCHLORIDE TABLET
DIRECTRX
----------
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 tablet exerts 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 WARNINGS AND
PRECAUTIONS (5.3)] .
2.1 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 BOXED WARNING and WARNINGS
AND
PRECAUTIONS (5.5)] .
Liver tests (serum alanine and aspartate aminotransferases, alkaline
phosphatase, and
total bilirubin) should be obtained prior to initiating pioglitazone
tablets. Routine periodic
monitoring of liver tests during treatment with pioglitazone tablets
are not
recommended in patients without liver disease. Patients who have liver
test abnormalities
prior to initiation of pioglitazone tablets or who are found to have
abnormal liver tests
while taking pioglitazone tablets should be managed as described under
Warnings and
Precautions [see WARNINGS AND PRECAUTIONS (5.3) and CLINICAL
PHARMACOLOGY
(12.3)] .
2.2