Pioglitazone HCL and Metformin 500 mg; 15 mg Tablet, 100-count
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- Great question. This pill combines two diabetes medicines that lower blood sugar in different ways. Pioglitazone makes your body's cells more sensitive to insulin so they can actua...
- What exactly does this medicine do, and why do I need two drugs in one pill?
- Always take it with a meal. The metformin in this tablet can cause nausea, diarrhea, or an upset stomach if you take it on an empty stomach. Eating while you take it helps a lot. T...
- Should I take this with food or on an empty stomach?
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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UNII 0WZ8WG20P6
Hypromellose 2910 is a plant-based cellulose derivative that acts as a thickener, binder, and film-coating agent. It helps control how quickly the medicine dissolves and protects the tablet or capsule from moisture and light.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII Q662QK8M3B
Polyethylene glycol 8000 is a synthetic polymer made from ethylene oxide. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and add bulk to the medicine.
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UNII U725QWY32X
Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
8 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $0.5971 | $59.71 / 100 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Pioglitazone and metformin hydrochloride 500 mg/1; 15 mg 33342-0176-09 | Macleods | 60 tablets | $0.322 | AB | Availability likely | — |
| Pioglitazone Hydrochloride and Metformin Hydrochloride 15 mg/1; 500 mg 57237-0217-60 | Rising | 60 tablets | $0.322 | AB | Availability likely | — |
| Pioglitazone Hydrochloride and Metformin Hydrochloride 15 mg/1; 500 mg 65862-0525-18 | Aurobindo | 180 tablets | $0.322 | AB | Availability likely | — |
| Pioglitazone HCL and Metformin HCL 500 mg/1; 15 mgthis 13668-0280-74 | Torrent | 100 tablets | — | AB | FDA listed | — |
| Pioglitazone and metformin hydrochloride 15 mg/1; 500 mg 71335-3019-01 | Bryant | 180 tablets | — | AB | FDA listed | — |
| Pioglitazole and metformin hydrochloride 15 mg/1; 500 mg 72162-2497-02 | Bryant | 180 tablets | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 13668-0280-05 | 500 TABLET in 1 BOTTLE (13668-280-05) | — | — | 2025-09-01 | Active |
| 13668-0280-10 | 1000 TABLET in 1 BOTTLE (13668-280-10) | — | — | 2025-09-01 | Active |
| 13668-0280-33 | 180 TABLET in 1 BOTTLE (13668-280-33) | $0.2301 / ea | $41.41 | 2025-09-01 | Active |
| 13668-0280-60 | 60 TABLET in 1 BOTTLE (13668-280-60) | $0.2301 / ea | $13.80 | 2025-09-01 | Active |
| 13668-0280-74 You're viewing this | 100 TABLET in 1 CARTON (13668-280-74) | — | — | 2025-09-01 | Active |
You're viewing one of 5 pack sizes for this product.
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Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
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| NDC identity (package / product / labeler codes) | ✓ Available |
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| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
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| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: CONGESTIVE HEART FAILURE and LACTIC ACIDOSIS See full prescribing information for complete boxed warning. Congestive Heart Failure • Thiazolidinediones, including pioglitazone, which is a component of pioglitazone and metformin hydrochloride tablets, cause or exacerbate congestive heart failure in some patients. (5.1) • After initiation of pioglitazone and metformin hydrochloride tablets, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema).
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. (5.1) • Pioglitazone and metformin hydrochloride tablets are not recommended in patients with symptomatic heart failure. (5.1) • Initiation of pioglitazone and metformin hydrochloride tablets in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated.
(4, 5.1) Lactic Acidosis • Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmia's. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally greater than 5 mcg/mL.
(5.2) • Risk factors include renal impairment, concomitant use of certain drugs, age ≥65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, hepatic impairment, and mitochondrial diseases. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high-risk groups are provided in the Full Prescribing Information. (5.2) • If lactic acidosis is suspected, discontinue pioglitazone and metformin hydrochloride tablets and institute general supportive measures in a hospital setting.
Prompt hemodialysis is recommended. (5.2) WARNING: CONGESTIVE HEART FAILURE and LACTIC ACIDOSIS Congestive Heart Failure • Thiazolidinediones, including pioglitazone, which is a component of pioglitazone and metformin hydrochloride tablets, cause or exacerbate congestive heart failure in some patients [see Warnings and Precautions (5.1)]. • After initiation of pioglitazone and metformin hydrochloride tablets, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema).
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 [see Warnings and Precautions (5.1)]. • Pioglitazone and metformin hydrochloride tablets are not recommended in patients with symptomatic heart failure [see Warnings and Precautions (5.1)]. • Initiation of pioglitazone and metformin hydrochloride tablets in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated [see Contraindications (4), Warnings and Precautions (5.1)].
Lactic Acidosis • Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmia's. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels gener…
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Pioglitazone and metformin hydrochloride tablets, are a combination of pioglitazone, a thiazolidinedione agonist of peroxisome proliferator receptor gamma, and metformin hydrochloride (HCl), a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1 ) Limitations of Use: Not recommended for treatment of type 1 diabetes or diabetic ketoacidosis. ( 1 ) Pioglitazone and metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Limitations of Use Pioglitazone and metformin hydrochloride tablets are not recommended to treat type 1 diabetes mellitus or diabetic ketoacidosis.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Obtain liver tests before initiation. If abnormal, use caution when treating with pioglitazone and metformin hydrochloride tablets, investigate the probable cause, treat (if possible), and follow appropriately. ( 2.1 ) • Take orally with meals to reduce gastrointestinal adverse reactions with metformin ( 2.1 ) • 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. ( 2.2 ) • Recommended starting dosage in patients with NYHA Class I or Class II congestive heart failure is 15 mg of pioglitazone and 850 mg of metformin HCl orally once daily. ( 2.4 ) • Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR).
( 2.2 ) o Contraindicated in patients with eGFR below 30 mL/min o Initiation is not recommended in patients with eGFR between 30 to 45 mL/min o Assess risk/benefit of continuing pioglitazone and metformin hydrochloride tablets if eGFR falls below 45 mL/min o Discontinue if eGFR falls below 30 mL/min • Monitor patients for adverse events related to fluid retention after initiation and dose increases. ( 2.4 ) • Pioglitazone and metformin hydrochloride tablets may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures.
(2.6)
2.1Important 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 [see Warnings and Precautions (5.5)] . • Pioglitazone and metformin hydrochloride tablets contains 15 mg of pioglitazone and 500 mg of metformin hydrochloride (HCl) and 15 mg of pioglitazone and 850 mg of metformin hydrochloride (HCl) in each tablet. • Take pioglitazone and metformin hydrochloride tablets 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.
2.2Recommended 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 Current Regimen Starting Dosage of pioglitazone and metformin hydrochloride tablets (15 mg of pioglitazone and 850 mg of metformin HCl per tablet)* Not treated with either pioglitazone or metformin HCl One tablet orally once daily Metformin HCl One tablet orally once or twice daily.
Select a dosage that is as close as possible to the current dosage of metformin HCl Pioglitazone One tablet orally once daily Pioglitazone and metformin HCl Select a dosage that is as close as possible to the current dosage of pioglitazone and metformin HCl while not exceeding three tablets orally per day. *For dosage recommendations for patients with renal impairment and/or congestive heart failure, see Dosage and Administration (2.3, 2.4) 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 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)] .
2.3Recommendations for Use in Patients with Renal Impairment • Assess renal function prior to initiation of pioglitazone and metformin hydrochloride tablets and periodically thereafter…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: 15 mg pioglitazone /500 mg metformin hydrochloride and 15 mg pioglitazone /850 mg metformin hydrochloride ( 3 ) • 15 mg of pioglitazone and 500 mg of metformin HCl tablets, USP: white to off-white colored, capsule shaped, biconvex, film coated tablets debossed with “15/500” on one side and “1280” on other side. • 15 mg of pioglitazone and 850 mg of metformin HCl tablets, USP: white to off-white colored, capsule shaped, biconvex, film coated tablets debossed with “15/850” on one side and “1281” on other side.
⛔ Contraindications ▾
4 CONTRAINDICATIONS • In patients with established New York Heart Association (NYHA) Class III or IV heart failure at the time of pioglitazone and metformin hydrochloride tablets initiation [see Boxed Warning]. ( 4 ) • In patients with severe renal impairment: (eGFR below 30 mL/min). ( 4 ) • In patients with a history of serious hypersensitivity to pioglitazone, metformin HCl, or any of the excipients in pioglitazone and metformin hydrochloride tablets.
( 4 ) • In patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis. ( 4 ) Pioglitazone and metformin hydrochloride tablets are contraindicated in patients with: • Established NYHA Class III or IV heart failure at the time of pioglitazone and metformin hydrochloride tablets initiation [see Boxed Warning]. • Severe renal impairment (eGFR below 30 mL/min) [see Warnings and Precautions (5.2)] . • A history of serious hypersensitivity to pioglitazone, metformin HCl, or any of the excipients in pioglitazone and metformin hydrochloride tablets. • Acute or chronic metabolic acidosis, including diabetic ketoacidosis [see Warnings and Precautions (5.2)] .
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • 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.
( 5.1 ) • Edema: Dose-related edema may occur. ( 5.3 ) • Hypoglycemia: Consider a lower dose of insulin or insulin secretagogue to reduce risk of hypoglycemia when used in combination with pioglitazone and metformin hydrochloride tablets. ( 5.4 ) • Hepatic Effects: Postmarketing reports of hepatic failure, sometimes fatal.
Causality cannot be excluded. If liver injury is detected, promptly interrupt pioglitazone and metformin hydrochloride tablets and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. Do not restart pioglitazone and metformin hydrochloride tablets if liver injury is confirmed and no alternate etiology can be found.
( 5.5 ) • Urinary Bladder Tumors: May increase the risk of bladder cancer. Do not use in patients with active bladder cancer. Use caution when using in patients with a prior history of bladder cancer.
( 5.6 ) • Fractures: Increased incidence in female patients. Apply current standards of care for assessing and maintaining bone health. ( 5.7 ) • Macular Edema: Postmarketing reports.
Recommend regular eye exams in all patients with diabetes according to current standards of care with prompt evaluation for acute visual changes. ( 5.8 ) • Vitamin B 12 Deficiency: Metformin may lower vitamin B 12 levels. Monitor hematologic parameters annually and vitamin B 12 at 2 to 3 year intervals and manage any abnormalities.
( 5.9 )
5.1Congestive Heart Failure Pioglitazone, like other thiazolidinediones, can cause dose-related fluid retention when used alone or in combination with other antidiabetic medications and is most common when pioglitazone is used in combination with insulin. Fluid retention may lead to or exacerbate congestive heart failure. Observe patients for 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 [see Boxed Warning, Contraindications (4), Adverse Reactions (6.1)] .
5.2Lactic Acidosis Lactic Acidosis There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypothermia, hypotension and resistant bradyarrhythmia's have occurred with severe acidosis. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally greater than 5 mcg/mL.
Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of pioglitazone and metformin hydrochloride tablets. In pioglitazone and metformin hydrochloride tablets-treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin HCl is dialyzable, with a clearance of up to 170 mL/min under good hemodynamic conditions).
Hemodialysis has often resulted in reversal of symptoms and recovery. Educate patients and their families about the symptoms of lactic acidosis and if these symptoms occur instruct them to disco…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Most common adverse reactions (>5%) are upper respiratory tract infection, edema, diarrhea, headache and weight gain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc. at 1-800-912-9561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 Deficiency [see Warnings and Precautions (5.9)]
6.1Clinical 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 (3.0%).
In the PROactive trial, the incidence of withdrawals due to adverse events was 9.0% 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. Common Adverse Events: 16 to 26 Week Monotherapy Trials A summary of the incidence and type of common adverse events reported in three pooled 16 to 26 week placebo-controlled monotherapy trials of pioglitazone is provided in Table 2.
Terms that are reported represent those that occurred at an incidence of >5% and more commonly in patients treated with pioglitazone than in patients who received placebo. None of these adverse events were related to the pioglitazone dose. Table 2: Three Pooled 16 to 26 Week Placebo-Controlled Clinical Trials of Pioglitazone Monotherapy: Adverse Events Reported at an Incidence >5% and More Commonly in Patients Treated with Pioglitazone than in Patients Treated with Placebo % of Patients Placebo N=259 Pioglitazone N=606 Upper Respiratory Tract Infection 8.5
13.2Headache 6.9
9.1Sinusitis 4.6
6.3Myalgia 2.7
5.4Pharyngitis 0.8
5.1Common Adverse Events: 16 to 24 Week Add-on Combination Therapy Trials A summary of the overall incidence and types of common adverse events reported in trials of pioglitazone add-on to metformin is provided in Table 3. Terms that are reported represent those that occurred at an incidence of >5% and more commonly with the highest tested dose of pioglitazone. Table 3: 16 to 24 Week Clinical Trials of Pioglitazone Add-on to Metformin 16 Week Placebo-Controlled Trial Adverse Events Reported in >5% of Patients and More…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • Strong CYP2C8 inhibitors (e.g., gemfibrozil): Limit pioglitazone and metformin hydrochloride tablets dose to 15 mg/850 mg daily. ( 7.1 ) • CYP2C8 inducers (e.g., rifampin) may decrease pioglitazone concentrations. ( 7.2 ) • Carbonic anhydrase inhibitors may increase risk of lactic acidosis.
Consider more frequent monitoring. ( 7.3 ) • Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine), may increase the accumulation of metformin. Consider the benefits and risks of concomitant use.
( 7.4 ) • Alcohol: Warn patients against excessive alcohol intake. ( 7.5 ) • Use of insulin secretagogues or insulin use may increase the risk for hypoglycemia and may require dose reduction. ( 7.6 ) • Topiramate may decrease pioglitazone concentrations.
( 7.8 )
7.1Strong 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 (t1/2) of pioglitazone. Therefore, the maximum recommended dosage of pioglitazone and metformin hydrochloride tablets is 15 mg of pioglitazone and 850 mg of metformin HCl once daily if used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)] .
7.2CYP2C8 Inducers An inducer of CYP2C8 (e.g., rifampin) may significantly decrease the exposure (AUC) of pioglitazone. Therefore, if an inducer of CYP2C8 is started or stopped during treatment with pioglitazone and metformin hydrochloride tablets, changes in diabetes treatment may be needed based on clinical response without exceeding the maximum recommended daily dosage of pioglitazone and metformin hydrochloride tablets (45 mg of pioglitazone and 2,550 mg of metformin HCl) [see Clinical Pharmacology (12.3)] .
7.3Carbonic Anhydrase Inhibitors Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently causes a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with pioglitazone and metformin hydrochloride may increase the risk for lactic acidosis. Consider more frequent monitoring of these patients.
7.4Drugs That Reduce Metformin Clearance Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology (12.3)] . Consider the benefits and risks of concomitant use.
7.5Alcohol Alcohol is known to potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake while receiving pioglitazone and metformin hydrochloride tablets.
7.6Insulin Secretagogues or Insulin Coadministration of pioglitazone and metformin hydrochloride with an insulin secretagogue (e.g., sulfonylurea) or insulin may increase the risk of hypoglycemia. If hypoglycemia occurs in a patient coadministered pioglitazone and metformin hydrochloride and an insulin secretagogue (e.g., sulfonylurea), the dose of the insulin secretagogue should be reduced.
7.7Drugs Affecting Glycemic Control Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. When such drugs are administered to a patient receiving pioglitazone and metformin hydrochloride tablets, the patient should be closely observed for loss of blood glucose control.
When such drugs are withdrawn from a patient receiving pioglitazone and metformin hydrochloride tabl…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy. ( 8.3 ) • Pediatrics: Safety and effectiveness have not been established. ( 8.4 ) • Geriatric Use: Assess renal function more frequently. ( 8.5 ) • Hepatic Impairment: Avoid use in patients with hepatic impairment. ( 8.7 )
8.1Pregnancy Risk Summary Limited data with pioglitazone and metformin hydrochloride or pioglitazone in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk (see Data) . There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations] .
In animal reproduction studies, no adverse developmental effects were observed when pioglitazone was administered to pregnant rats and rabbits during organogenesis at exposures up to 5 and 35 times the 45 mg clinical dose, respectively, based on body surface area. No adverse developmental effects were observed when metformin was administered to pregnant Sprague Dawley rats and rabbits during the period of organogenesis at doses up to 2 to 6 times, respectively, a 2,000 mg clinical dose, based on body surface area (see Data) .
The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20 to 25% in women with a HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity. Data Human Data Published data from postmarketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy.
However, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Animal Data Pioglitazone and Metformin HCl Animal reproduction studies were not conducted with the combined products in pioglitazone and metformin hydrochloride tablets. The following data are based on studies conducted with the individual components of pioglitazone and metformin hydrochloride tablets.
Pioglitazone Pioglitazone administered to pregnant rats during organogenesis did not cause adverse developmental effects at a dose of 20 mg/kg (~5 times the 45 mg clinical dose), but delayed parturition and reduced embryo-fetal viability at 40 and 80 mg/kg, or ≥9 times the 45 mg clinical dose, by body surface area. In pregnant rabbits administered pioglitazone during organogenesis, no adverse developmental effects were observed at 80 mg/kg (~35 times the 45 mg clinical dose), but reduced embryo-fetal viability at 160 mg/kg, or ~69 times the 45 mg clinical dose, by body surface area.
When pregnant rats received pioglitazone during late gestation and lactation, delayed postnatal development, attributed to decreased body weight, occurred in offspring at maternal doses of 10 mg/kg and above or ≥2 times the 45 mg clinical dose, by body surface area. Metformin HCl Metformin HCl did not cause adverse developmental effects when administered to pregnant Sprague Dawley rats and rabbits up to 600 mg/k…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Limited data with pioglitazone and metformin hydrochloride or pioglitazone in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk (see Data) . There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations] .
In animal reproduction studies, no adverse developmental effects were observed when pioglitazone was administered to pregnant rats and rabbits during organogenesis at exposures up to 5 and 35 times the 45 mg clinical dose, respectively, based on body surface area. No adverse developmental effects were observed when metformin was administered to pregnant Sprague Dawley rats and rabbits during the period of organogenesis at doses up to 2 to 6 times, respectively, a 2,000 mg clinical dose, based on body surface area (see Data) .
The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20 to 25% in women with a HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity. Data Human Data Published data from postmarketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy.
However, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Animal Data Pioglitazone and Metformin HCl Animal reproduction studies were not conducted with the combined products in pioglitazone and metformin hydrochloride tablets. The following data are based on studies conducted with the individual components of pioglitazone and metformin hydrochloride tablets.
Pioglitazone Pioglitazone administered to pregnant rats during organogenesis did not cause adverse developmental effects at a dose of 20 mg/kg (~5 times the 45 mg clinical dose), but delayed parturition and reduced embryo-fetal viability at 40 and 80 mg/kg, or ≥9 times the 45 mg clinical dose, by body surface area. In pregnant rabbits administered pioglitazone during organogenesis, no adverse developmental effects were observed at 80 mg/kg (~35 times the 45 mg clinical dose), but reduced embryo-fetal viability at 160 mg/kg, or ~69 times the 45 mg clinical dose, by body surface area.
When pregnant rats received pioglitazone during late gestation and lactation, delayed postnatal development, attributed to decreased body weight, occurred in offspring at maternal doses of 10 mg/kg and above or ≥2 times the 45 mg clinical dose, by body surface area. Metformin HCl Metformin HCl did not cause adverse developmental effects when administered to pregnant Sprague Dawley rats and rabbits up to 600 mg/kg/day during the period of organogenesis. This represents an exposure of about 2 to 6 times a 2,000 mg clinical dose based on body surface area (mg/m 2 ) for rats and rabbits, respectively.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of pioglitazone and metformin hydrochloride in pediatric patients have not been established. Pioglitazone and metformin hydrochloride 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 Warnings and Precautions (5.1, 5.3, 5.6, 5.7)].
🧓 Geriatric Use ▾
8.5Geriatric Use Pioglitazone 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. In the two pooled 16 to 24 week add-on to metformin trials, 155 patients (15.5%) treated with pioglitazone were ≥65 years old and 19 (1.9%) were ≥75 years old.
In the two pooled 16 to 24 week add-on to insulin trials, 272 patients (25.4%) treated with pioglitazone were ≥65 years old and 22 (2.1%) were ≥75 years old. In PROactive Trial, 1,068 patients (41.0%) treated with pioglitazone were ≥65 years old and 42 (1.6%) were ≥75 years old. In pharmacokinetic studies with pioglitazone, no significant differences were observed in pharmacokinetic parameters between elderly and younger patients [see Clinical Pharmacology (12.3)] .
Although clinical experiences have not identified differences in effectiveness and safety between the elderly (≥65 years) and younger patients, these conclusions are limited by small sample sizes for patients ≥75 years old. Metformin HCl Controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between the elderly and young patients.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis. Assess renal function more frequently in elderly patients [see Warnings and Precautions (5.2), Dosage and Administration (2.2)] .
🆘 Overdosage ▾
10 OVERDOSAGE Pioglitazone 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.
Metformin HCl Overdose of metformin HCl has occurred, including ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin HCl has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases [see Warnings and Precautions (5.2)] .
Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated metformin from patients in whom metformin overdosage is suspected. In the event of overdosage, contact the Poison Help Line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.
Appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Pioglitazone and metformin hydrochloride tablets combine two antihyperglycemic agents: pioglitazone and metformin. Pioglitazone Pioglitazone is a thiazolidinedione that depends on the presence of insulin for its mechanism of action. Pioglitazone decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output.
Pioglitazone is not an insulin secretagogue. Pioglitazone is an agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). PPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle, and liver.
Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism. In animal models of diabetes, pioglitazone reduces the hyperglycemia, hyperinsulinemia, and hypertriglyceridemia characteristic of insulin-resistant states such as type 2 diabetes mellitus. The metabolic changes produced by pioglitazone result in increased responsiveness of insulin-dependent tissues and are observed in numerous animal models of insulin resistance.
Because pioglitazone enhances the effects of circulating insulin (by decreasing insulin resistance), it does not lower blood glucose in animal models that lack endogenous insulin. Metformin HCl Metformin HCl improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Metformin does not produce hypoglycemia in either patients with type 2 diabetes mellitus or healthy subjects [except in specific circumstances, see Warnings and Precautions (5.4) ] and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.
12.2Pharmacodynamics Pioglitazone Clinical studies demonstrate that pioglitazone improves insulin sensitivity in insulin-resistant patients. Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal and improves hepatic sensitivity to insulin. In patients with type 2 diabetes mellitus, the decreased insulin resistance produced by pioglitazone results in lower plasma glucose concentrations, lower plasma insulin concentrations, and lower HbA1c values.
In controlled clinical trials, pioglitazone had an additive effect on glycemic control when used in combination with a sulfonylurea, metformin, or insulin [see Clinical Studies (14)] . Patients with lipid abnormalities were included in clinical trials with pioglitazone. Overall, patients treated with pioglitazone had mean decreases in serum triglycerides, mean increases in HDL cholesterol, and no consistent mean changes in LDL and total cholesterol.
There is no conclusive evidence of macrovascular benefit with pioglitazone [see Adverse Reactions (6.1)] . In a 26 week, placebo-controlled, dose-ranging monotherapy study, mean serum triglycerides decreased in the 15 mg, 30 mg, and 45 mg pioglitazone dose groups compared to a mean increase in the placebo group. Mean HDL cholesterol increased to a greater extent in patients treated with pioglitazone than in the placebo-treated patients.
There were no consistent differences for LDL and total cholesterol in patients treated with pioglitazone compared to placebo (see Table 17) . Table 17:Lipids in a 26 Week Placebo-Controlled Monotherapy Dose-Ranging Study * Adjusted for baseline, pooled center, and pooled center by treatment interaction. † p < 0.05 vs placebo. Placebo Pioglitazone 15 mg Once Daily Pioglitazone 30 mg Once Daily Pioglitazone 45 mg Once Daily Triglycerides ( mg / dL ) N=79 N=79 N=84 N=77 Baseline (mean) 2…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Pioglitazone and metformin hydrochloride tablets combine two antihyperglycemic agents: pioglitazone and metformin. Pioglitazone Pioglitazone is a thiazolidinedione that depends on the presence of insulin for its mechanism of action. Pioglitazone decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output.
Pioglitazone is not an insulin secretagogue. Pioglitazone is an agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). PPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle, and liver.
Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism. In animal models of diabetes, pioglitazone reduces the hyperglycemia, hyperinsulinemia, and hypertriglyceridemia characteristic of insulin-resistant states such as type 2 diabetes mellitus. The metabolic changes produced by pioglitazone result in increased responsiveness of insulin-dependent tissues and are observed in numerous animal models of insulin resistance.
Because pioglitazone enhances the effects of circulating insulin (by decreasing insulin resistance), it does not lower blood glucose in animal models that lack endogenous insulin. Metformin HCl Metformin HCl improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Metformin does not produce hypoglycemia in either patients with type 2 diabetes mellitus or healthy subjects [except in specific circumstances, see Warnings and Precautions (5.4) ] and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Pioglitazone and metformin hydrochloride tablets, USP are available in 15 mg pioglitazone (as the base)/500 mg metformin HCl and 15 mg pioglitazone (as the base)/850 mg metformin HCl tablets as follows: 15 mg/500 mg tablet: white to off-white colored, capsule shaped, biconvex, film coated tablets debossed with "15/500" on one side and "1280" on other side, available in: Bottles of 60 NDC 13668-280-60 Bottles of 180 NDC 13668-280-33 Bottles of 500 NDC 13668-280-05 Bottles of 1000 NDC 13668-280-10 15 mg/850 mg tablet: white to off-white colored, capsule shaped, biconvex, film coated tablets debossed with "15/850" on one side and "1281" on other side, available in: Bottles of 60 NDC 13668-281-60 Bottles of 180 NDC 13668-281-33 Bottles of 500 NDC 13668-281-05 Bottles of 750 NDC 13668-281-49 Storage Store at 20° to 25° C (68° to 77° F); excursions permitted to 15° to 30° C (59° to 86° F) [see USP Controlled Room Temperature].
Keep container tightly closed, and protect from moisture.
📋 Description ▾
11 DESCRIPTION Pioglitazone and metformin hydrochloride tablets, USP are a thiazolidinediones and biguanide combination product that contains two oral antidiabetic medications: pioglitazone HCl and metformin HCl. Pioglitazone [(±)-5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy]phenyl]methyl]-2,4-] thiazolidinedione monohydrochloride contains one asymmetric carbon, and the compound is synthesized and used as the racemic mixture. The two enantiomers of pioglitazone interconvert in vivo .
No differences were found in the pharmacologic activity between the two enantiomers. The structural formula is as shown: Pioglitazone HCl, USP is an odorless white crystalline powder that has a molecular formula of C 19 H 20 N 2 O 3 S•HCl and a molecular weight of 392.90 daltons. It is soluble in N,N -dimethylformamide, slightly soluble in anhydrous ethanol, very slightly soluble in acetone and acetonitrile, practically insoluble in water, and insoluble in ether.
Metformin HCl ( N,N -dimethylimidodicarbonimidic diamide HCl), USP is a white crystalline powder with a molecular formula of C 4 H 11 N 5 •HCl and a molecular weight of 165.62. Metformin HCl is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pKa of metformin is 12.4.
The pH of a 1% aqueous solution of metformin HCl is 6.68. The structural formula is as shown: Pioglitazone and metformin hydrochloride tablets, USP are available as a tablet for oral administration containing 15 mg pioglitazone (as the base) with 500 mg metformin hydrochloride (15 mg/500 mg) or 15 mg pioglitazone (as the base) with 850 mg metformin hydrochloride (15 mg/850 mg) formulated with the following excipients: croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, talc, and titanium dioxide.
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💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). • Congestive Heart Failure : Inform patients of the signs and symptoms of heart failure. Instruct patients who experience an unusually rapid increase in weight or edema, shortness of breath, or other symptoms of heart failure while on pioglitazone and metformin hydrochloride tablets to immediately report these symptoms to their healthcare provider. [see Warnings and Precautions (5.1)] . • Lactic Acidosis : Explain to patients the risks of lactic acidosis, its symptoms and conditions that predispose to its development, as noted in the Warnings and Precautions (5.2) section.
Advise patients to discontinue pioglitazone and metformin hydrochloride tablets immediately and to promptly notify their healthcare professional if unexplained hyperventilation, myalgia, gastrointestinal symptoms, malaise, unusual somnolence, or other nonspecific symptoms occur. Counsel patients against excessive alcohol intake and inform patients about the importance of regular testing of renal function while receiving pioglitazone and metformin hydrochloride tablets. Inform patients about the importance of regular testing of renal function and hematologic parameters when receiving treatment with pioglitazone and metformin hydrochloride tablets Instruct patients to inform their doctor that they are taking pioglitazone and metformin hydrochloride tablets prior to any surgical or radiological procedure, as temporary discontinuation of pioglitazone and metformin hydrochloride tablets may be required until renal function has been confirmed to be normal. • Edema : Inform patients that pioglitazone and metformin hydrochloride tablets use can lead to new-onset or worsening of edema.
Instruct patients to immediately report symptoms of rapid weight increase or worsening edema to their healthcare provider [see Warnings and Precautions (5.3)] . • Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues : Inform patients that the risk of hypoglycemia is increased when pioglitazone and metformin hydrochloride tablets is used with insulin or insulin secretagogues (such as a sulfonylurea). Educate patients on the signs and symptoms of hypoglycemia [see Warnings and Precautions (5.4)] . • Hepatic Effects : Instruct patients to promptly stop taking pioglitazone and metformin hydrochloride tablets and seek immediate medical advice if they experience signs or symptoms of liver injury (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or dark urine) [see Warnings and Precautions (5.5)] . • Urinary Bladder Tumors : Advise patients to promptly report any hematuria, dysuria or urinary urgency that develops or increases during treatment as these may be due to bladder cancer [see Warnings and Precautions (5.6)] . • Fractures : Inform female patients about the risk of fractures while taking pioglitazone and metformin hydrochloride tablets.
Provide them with information on factors that may contribute to fracture risk [see Warnings and Precautions (5.7)] . • Macular Edema : Educate patients on the signs and symptoms of macular edema and advise them to seek medical attention from an ophthalmologist if they experience symptoms of macular edema [see Warnings and Precautions (5.8)] . • Vitamin B 12 Deficiency : Inform patients about the importance of obtaining regular hematological laboratory monitoring while receiving pioglitazone and metformin hydrochloride tablets [see Warnings and Precautions (5.9)] . • Females of Reproductive Age : Inform female patients that treatment with pioglitazone and metformin hydrochloride tablets may result in an unintended pregnancy in some premenopausal anovulatory females due to its effect on ovulation [see Use in Specific Populations (8.3)]. • Missed Dosage : Instruct patients if a dose is missed, not to double their next dose.
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💬 Medication Guide ▾
MEDICATION GUIDE PIOGLITAZONE AND METFORMIN HYDROCHLORIDE (PYE o GLI ta zone and met FOR min HYE-droe-KLOR-ide) TABLETS, USP, for oral use Read this Medication Guide carefully before you start taking pioglitazone and metformin hydrochloride tablets and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.
If you have any questions about pioglitazone and metformin hydrochloride tablets, ask your healthcare provider or pharmacist. What is the most important information I should know about pioglitazone and metformin hydrochloride tablets ? Pioglitazone and metformin hydrochloride tablets can cause serious side effects, including: Heart failure.
Pioglitazone, one of the medicines in pioglitazone and metformin hydrochloride 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.
Before you start taking pioglitazone and metformin hydrochloride tablets: Tell your healthcare provider if you have ever had heart failure or have problems with your kidneys Call your healthcare provider right away if you have any of the following: o increasing shortness of breath or trouble breathing, especially when you lie down o an unusually fast increase in weight o swelling or fluid retention, especially in the ankles or legs o unusual tiredness These may be symptoms of heart failure. Lactic acidosis. Metformin, one of the medicines in pioglitazone and metformin hydrochloride tablets, can cause a rare but serious condition called lactic acidosis (a buildup of an acid in the blood) that can cause death.
Lactic acidosis is a medical emergency and must be treated in the hospital. Stop taking pioglitazone and metformin hydrochloride tablets and call your healthcare provider right away if you have any of the following symptoms, which could be signs of lactic acidosis: o feel very weak or tired o have unusual (not normal) muscle pain o have trouble breathing o have unusual sleepiness or sleep longer than usual o have unexplained stomach or intestinal problems with nausea, vomiting, or diarrhea o feel cold, especially in your arms and legs o feel dizzy or lightheaded o have a slow or irregular heartbeat Most people who have had lactic acidosis with metformin have other things that, combined with the metformin, led to the lactic acidosis.
Tell your healthcare provider if you have any of the following, because you have a higher chance for getting lactic acidosis with pioglitazone and metformin hydrochloride tablets if you: o have severe kidney problems or your kidneys are affected by certain x-ray tests that use injectable dye. o have liver problems o drink alcohol very often, or drink a lot of alcohol in short-term ("binge" drinking) o get dehydrated (lose a large amount of body fluids). This can happen if you are sick with a fever, vomiting, or diarrhea.
Dehydration can also happen when you sweat a lot with activity or exercise and do not drink enough fluids o have surgery o have a heart attack, severe infection, or stroke o are 65 years of age or older o have a genetically inherited disease affecting mitochondria (the energy-producing parts within cells) such as mitochondrial encephalomyopathy with lactic acidosis, and stroke-like episodes (MELAS) syndrome and maternally inherited diabetes and deafness (MIDD). The best way to keep from having a problem with lactic acidosis from metformin is to tell your healthcare provider if you have any of the problems in the list above.
Your healthcare provider may decide to stop your pioglitazone and metformin hydrochloride tablets for a while if you have any of these things. Pioglitazone and metformin hydrochloride tablets can have other serious side effects. See “What are the possible si…