Actoplus Met XR

Name: Actoplus Met XR

Commonly used brand name(s)

In the U.S.

  • Actoplus Met
  • Actoplus Met XR

Available Dosage Forms:

  • Tablet
  • Tablet, Extended Release

Therapeutic Class: Hypoglycemic

Chemical Class: Metformin

Before Using Actoplus Met XR

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of pioglitazone and metformin combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of pioglitazone and metformin combination in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution and an adjustment in the dose for patients receiving pioglitazone and metformin combination.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Acetrizoic Acid
  • Diatrizoate
  • Ethiodized Oil
  • Iobenzamic Acid
  • Iobitridol
  • Iocarmic Acid
  • Iocetamic Acid
  • Iodamide
  • Iodipamide
  • Iodixanol
  • Iodohippuric Acid
  • Iodopyracet
  • Iodoxamic Acid
  • Ioglicic Acid
  • Ioglycamic Acid
  • Iohexol
  • Iomeprol
  • Iopamidol
  • Iopanoic Acid
  • Iopentol
  • Iophendylate
  • Iopromide
  • Iopronic Acid
  • Ioseric Acid
  • Iosimide
  • Iotasul
  • Iothalamate
  • Iotrolan
  • Iotroxic Acid
  • Ioxaglate
  • Ioxitalamic Acid
  • Ipodate
  • Metrizamide
  • Metrizoic Acid
  • Tyropanoate Sodium

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acarbose
  • Aspirin
  • Balofloxacin
  • Besifloxacin
  • Bupropion
  • Chlorpropamide
  • Ciprofloxacin
  • Dasabuvir
  • Dofetilide
  • Dolutegravir
  • Enoxacin
  • Fleroxacin
  • Flumequine
  • Gatifloxacin
  • Gemifloxacin
  • Glimepiride
  • Glipizide
  • Glyburide
  • Ifosfamide
  • Insulin
  • Insulin Aspart, Recombinant
  • Insulin Bovine
  • Insulin Degludec
  • Insulin Detemir
  • Insulin Glargine, Recombinant
  • Insulin Glulisine
  • Insulin Lispro, Recombinant
  • Ioversol
  • Lanreotide
  • Levofloxacin
  • Lomefloxacin
  • Metformin
  • Moxifloxacin
  • Nadifloxacin
  • Nateglinide
  • Nifedipine
  • Norfloxacin
  • Octreotide
  • Ofloxacin
  • Ombitasvir
  • Paritaprevir
  • Pasireotide
  • Pazufloxacin
  • Pefloxacin
  • Pioglitazone
  • Piperaquine
  • Pixantrone
  • Prulifloxacin
  • Repaglinide
  • Ritonavir
  • Rufloxacin
  • Sparfloxacin
  • Thioctic Acid
  • Tolazamide
  • Tolbutamide
  • Tolvaptan
  • Tosufloxacin
  • Vandetanib

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acebutolol
  • Atenolol
  • Atorvastatin
  • Betaxolol
  • Bisoprolol
  • Bitter Melon
  • Carteolol
  • Carvedilol
  • Celiprolol
  • Esmolol
  • Fenugreek
  • Furazolidone
  • Glucomannan
  • Guar Gum
  • Iproniazid
  • Isocarboxazid
  • Ketoconazole
  • Labetalol
  • Levobunolol
  • Linezolid
  • Methylene Blue
  • Metipranolol
  • Metoprolol
  • Moclobemide
  • Nadolol
  • Nebivolol
  • Nialamide
  • Nilotinib
  • Oxprenolol
  • Patiromer
  • Penbutolol
  • Phenelzine
  • Pindolol
  • Practolol
  • Procarbazine
  • Propranolol
  • Psyllium
  • Ranolazine
  • Rasagiline
  • Rifampin
  • Safinamide
  • Selegiline
  • Sotalol
  • Timolol
  • Topiramate
  • Tranylcypromine
  • Verapamil

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Adrenal gland problem (underactive) or
  • Alcohol abuse, history of or
  • Cardiovascular collapse (shock) or
  • Congestive heart failure, acute or unstable or
  • Dehydration, severe or
  • Heart attack, acute or
  • Kidney problems or
  • Liver disease or
  • Pituitary gland problem (underactive) or
  • Poorly nourished condition or
  • Sepsis (severe infection) or
  • Weakened physical condition—Use with caution. May cause side effects to become worse.
  • Anemia (low red blood cells) or
  • Diabetic macular edema (swelling of the back of the eye) or
  • Edema (fluid retention or swelling) or
  • Heart disease or
  • Liver disease or
  • Vitamin B12 deficiency—Use with caution. May make these conditions worse.
  • Bladder cancer, active or
  • Diabetic ketoacidosis (high ketones and acid in the blood) or
  • Heart failure, severe or
  • Kidney disease, severe or
  • Liver disease, active or
  • Metabolic acidosis (acid in the blood) or
  • Type I diabetes—Should not be used in patients with these conditions.
  • Fever or
  • Infection or
  • Surgery or
  • Trauma—Use with caution. These conditions may cause problems with blood sugar control.

What do I need to tell my doctor BEFORE I take Actoplus Met XR?

  • If you have an allergy to metformin, pioglitazone, or any other part of Actoplus Met XR.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Acidic blood problem, bladder cancer, or type 1 diabetes.
  • If you have any of these health problems: Kidney disease or liver disease.
  • If you have had a recent heart attack or stroke.
  • If you are not able to eat or drink like normal, including before certain procedures or surgery.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Actoplus Met XR with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Contraindications

  • Initiation in patients with established NYHA Class III or IV heart failure [see Boxed Warning].
  • Severe renal impairment ( eGFR below 30 mL/min/1.73 m2) [see Warnings and Precautions (5.2)].
  • Use in patients with known hypersensitivity to pioglitazone, metformin or any other component of Actoplus Met XR.
  • Metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin.

Actoplus Met XR Description

Actoplus Met XR tablets are a thiazolidinedione and biguanide combination product that contains two oral anti-diabetic medications: pioglitazone and metformin hydrochloride (extended-release).

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 hydrochloride

Pioglitazone hydrochloride is an odorless white crystalline powder that has a molecular formula of C19H20N2O3S•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 hydrochloride (N,N-dimethylimidodicarbonimidic diamide hydrochloride) is a white crystalline powder with a molecular formula of C4H11N5•HCl and a molecular weight of 165.62. Metformin hydrochloride 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 hydrochloride is 6.68. The structural formula is as shown:

metformin hydrochloride

Actoplus Met XR is available as a tablet for oral administration containing 15 mg pioglitazone (as the base) and 1000 mg metformin hydrochloride (15 mg/1000 mg) or 30 mg pioglitazone (as the base) and 1000 mg metformin hydrochloride (30 mg/1000 mg) formulated with the following excipients: candelilla wax, cellulose acetate, povidone, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, hypromellose, polyethylene glycols (PEG 400, PEG 8000), sodium lauryl sulfate, titanium dioxide, and triacetin. Tablets are imprinted with ink containing shellac, iron oxide red (15 mg/1000 mg strength only), FD&C Blue No. 2 Lake (30 mg/1000 mg strength only), propylene glycol, and ammonium hydroxide.

SYSTEM COMPONENTS AND PERFORMANCE

Actoplus Met XR consists of an extended-release metformin core coated tablet with an immediate-release pioglitazone layer. The tablet is similar in appearance to other film-coated orally administered tablets but it consists of an osmotically active core formulation that is surrounded by a semipermeable membrane and coated with a pioglitazone drug layer. Two laser drilled exit ports exist in the membrane, one on either side of the tablet. The core formulation is composed primarily of drug with small concentrations of excipients. The semipermeable membrane is permeable to water but not to higher molecular weight components of biological fluids. Upon ingestion, the pioglitazone layer is dissolved; water is then taken up through the membrane, which in turn dissolves the metformin and excipients in the core formulation. The dissolved metformin and excipients exit through the laser drilled ports in the membrane. The rate of drug delivery is constant and dependent upon the maintenance of a constant osmotic gradient across the membrane. This situation exists so long as there is undissolved metformin present in the core tablet. Following the dissolution of the core materials, the rate of drug delivery slowly decreases until the osmotic gradient across the membrane falls to zero at which time delivery ceases. The membrane coating remains intact during the transit of the dosage form through the gastrointestinal tract and is excreted in the feces.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Actoplus Met XR

No animal studies have been conducted with Actoplus Met XR. The following data are based on findings in studies performed with pioglitazone or metformin individually.

Pioglitazone

A two-year carcinogenicity study was conducted in male and female rats at oral doses up to 63 mg/kg (approximately 14 times the maximum recommended human oral dose of 45 mg based on mg/m2). Drug-induced tumors were not observed in any organ except for the urinary bladder of male rats. Benign and/or malignant transitional cell neoplasms were observed in male rats at 4 mg/kg/day and above (approximately equal to the maximum recommended human oral dose based on mg/m2). Urinary calculi with subsequent irritation and hyperplasia were postulated as the mechanism for bladder tumors observed in male rats. A two-year mechanistic study in male rats utilizing dietary acidification to reduce calculi formation was completed in 2009. Dietary acidification decreased but did not abolish the hyperplastic changes in the bladder. The presence of calculi exacerbated the hyperplastic response to pioglitazone but was not considered the primary cause of the hyperplastic changes.

The relevance to humans of the bladder findings in the male rat cannot be excluded.

A two-year carcinogenicity study was also conducted in male and female mice at oral doses up to 100 mg/kg/day (approximately 11 times the maximum recommended human oral dose based on mg/m2). No drug-induced tumors were observed in any organ.

Pioglitazone hydrochloride was not mutagenic in a battery of genetic toxicology studies, including the Ames bacterial assay, a mammalian cell forward gene mutation assay (CHO/HPRT and AS52/XPRT), an in vitro cytogenetics assay using CHL cells, an unscheduled DNA synthesis assay, and an in vivo micronucleus assay.

No adverse effects upon fertility were observed in male and female rats at oral doses up to 40 mg/kg pioglitazone hydrochloride daily prior to and throughout mating and gestation (approximately nine times the maximum recommended human oral dose based on mg/m2).

Metformin hydrochloride

Long-term carcinogenicity studies have been performed in rats (dosing duration of 104 weeks) and mice (dosing duration of 91 weeks) at doses up to and including 900 mg/kg/day and 1500 mg/kg/day, respectively. These doses are both approximately four times a human daily dose of 2000 mg of the metformin component of Actoplus Met XR based on body surface area comparisons. No evidence of carcinogenicity with metformin was found in either male or female mice. Similarly, there was no tumorigenic potential observed with metformin in male rats. There was, however, an increased incidence of benign stromal uterine polyps in female rats treated with 900 mg/kg/day.

There was no evidence of mutagenic potential of metformin in the following in vitro tests: Ames test (S. typhimurium), gene mutation test (mouse lymphoma cells), or chromosomal aberrations test (human lymphocytes). Results in the in vivo mouse micronucleus test were also negative.

Fertility of male or female rats was unaffected by metformin when administered at doses as high as 600 mg/kg/day, which is approximately three times the maximum recommended human daily dose of the metformin component of Actoplus Met XR based on body surface area comparisons.

Animal Toxicology and/or Pharmacology

Heart enlargement has been observed in mice (100 mg/kg), rats (4 mg/kg and above) and dogs (3 mg/kg) treated orally with pioglitazone hydrochloride (approximately 11, 1, and 2 times the maximum recommended human oral dose for mice, rats, and dogs, respectively, based on mg/m2). In a one-year rat study, drug-related early death due to apparent heart dysfunction occurred at an oral dose of 160 mg/kg/day (approximately 35 times the maximum recommended human oral dose based on mg/m2). Heart enlargement was seen in a 13-week study in monkeys at oral doses of 8.9 mg/kg and above (approximately 4 times the maximum recommended human oral dose based on mg/m2), but not in a 52-week study at oral doses up to 32 mg/kg (approximately 13 times the maximum recommended human oral dose based on mg/m2).

Patient Counseling Information

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. • Tell patients to promptly report any sign of macroscopic hematuria or other symptoms such as dysuria or urinary urgency that develop or increase during treatment as these may be due to bladder cancer. • 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 Actoplus Met XR immediately and to promptly notify their healthcare professional if unexplained hyperventilation, myalgia, gastrointestinal symptoms, malaise, unusual somnolence or other nonspecific symptoms occur. Instruct patients to inform their doctor that they are taking Actoplus Met XR prior to any surgical or radiological procedure, as temporary discontinuation of Actoplus Met XR may be required until renal function has been confirmed to be normal. • Counsel patients against excessive alcohol intake while receiving Actoplus Met XR. • Inform patients to immediately report symptoms of an unusually rapid increase in weight or edema, shortness of breath or other symptoms of heart failure while receiving Actoplus Met XR. • Tell patients to promptly stop taking Actoplus Met XR and seek immediate medical advice if there is unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or dark urine as these symptoms may be due to hepatotoxicity. • Inform patients about the importance of regular testing of renal function and hematologic parameters when receiving treatment with Actoplus Met XR. • Inform female patients that treatment with Actoplus Met XR may result in an unintended pregnancy in some premenopausal anovulatory females due to its effect on ovulation [see Use in Specific Populations (8.3)]. • Patients should be advised to notify their health practitioner or call the Poison Control Center immediately in case of Actoplus Met XR overdose. • Combination antihyperglycemic therapy may cause hypoglycemia. When initiating Actoplus Met XR, the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and their family members. • Patients should be told to take Actoplus Met XR as prescribed and instructed that any change in dosing should only be done if directed by their physician. If a dose is missed on one day, the dose should not be doubled the following day.

Distributed by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

ACTOS and Actoplus Met XR are trademarks of Takeda Pharmaceutical Company Limited registered with the U.S. Patent and Trademark Office and used under license by Takeda Pharmaceuticals America, Inc.

All other trademarks are the property of their respective owners.

©2009 - 2016 Takeda Pharmaceuticals America, Inc.

AMX002 R10

MEDICATION GUIDE

Actoplus Met XR (ak-TŌ-plus-met eX-R)
(pioglitazone and metformin hydrochloride extended-release) tablets

Read this Medication Guide carefully before you start taking Actoplus Met XR 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 Actoplus Met XR, ask your doctor or pharmacist.

What is the most important information I should know about Actoplus Met XR?

Actoplus Met XR can cause serious side effects, including:

• new or worse heart failure. Pioglitazone, one of the medicines in Actoplus Met XR, 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 Actoplus Met XR 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, Actoplus Met XR 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 • lactic acidosis. Metformin, one of the medicines in Actoplus Met XR, 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.   Call your doctor right away if you have any of the following symptoms, which could be signs of lactic acidosis: • you feel cold in your hands or feet • you feel dizzy or lightheaded • you have a slow or irregular heartbeat • you feel very weak or tired • you have unusual (not normal) muscle pain • you have trouble breathing • you feel sleepy or drowsy • you have stomach pains, nausea or vomiting

Most people who have had lactic acidosis with metformin have other things that, combined with the metformin, led to the lactic acidosis. Tell your doctor if you have any of the following, because you have a higher chance for getting lactic acidosis with Actoplus Met XR if you:

• have severe kidney problems or your kidneys are affected by certain x-ray tests that use injectable dye • have liver problems • drink alcohol very often, or drink a lot of alcohol in short-term "binge" drinking • 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 • have surgery • have a heart attack, severe infection, or stroke

The best way to keep from having a problem with lactic acidosis from metformin is to tell your doctor if you have any of the problems in the list above. Your doctor may decide to stop your Actoplus Met XR for a while if you have any of these things.

Actoplus Met XR can have other serious side effects. See "What are the possible side effects of Actoplus Met XR?"

What is Actoplus Met XR?

Actoplus Met XR contains 2 prescription diabetes medicines called pioglitazone (ACTOS) and metformin hydrochloride extended-release. Actoplus Met XR can be used with diet and exercise to improve blood sugar (glucose) control in adults with type 2 diabetes.

Actoplus Met XR is not for people with type 1 diabetes.

Actoplus Met XR is not for people with diabetic ketoacidosis (increased ketones in your blood or urine).

It is not known if Actoplus Met XR is safe and effective in children under the age of 18. Actoplus Met XR is not recommended for use in children.

Who should not take Actoplus Met XR?

See "What is the most important information I should know about Actoplus Met XR?"

Do not take Actoplus Met XR if you:

• have severe heart failure • are allergic to pioglitazone, metformin or any of the ingredients in Actoplus Met XR. See the end of this Medication Guide for a complete list of ingredients in Actoplus Met XR • have severe kidney problems • have a condition called metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin

Tell your doctor before taking Actoplus Met XR if you have any of these conditions.

What should I tell my doctor before taking Actoplus Met XR?

Before you take Actoplus Met XR, tell your doctor if you:

• have heart failure • have severe kidney problems • are going to have dye injected into a vein for an x-ray, CAT scan, heart study, or other type of scanning • will be undergoing a surgical procedure • drink a lot of alcohol (all the time or short binge drinking) • have type 1 ("juvenile") diabetes or had diabetic ketoacidosis • have a type of diabetic eye disease that causes swelling in the back of the eye (macular edema) • have liver problems • have or have had cancer of the bladder • are pregnant or plan to become pregnant. It is not known if Actoplus Met XR can harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant about the best way to control your blood glucose levels while pregnant • are a premenopausal woman (before the "change of life"), who does not have periods regularly or at all. Actoplus Met XR may increase your chance of becoming pregnant. Talk to your doctor about birth control choices while taking Actoplus Met XR. Tell your doctor right away if you become pregnant while taking Actoplus Met XR • are breast-feeding or plan to breast-feed. It is not known if Actoplus Met XR passes into your milk and if it can harm your baby. Talk to your doctor about the best way to control your blood glucose levels while breast-feeding

Tell your doctor about all the medicines you take including prescription and over the counter medicines, vitamins, and herbal supplements.

Actoplus Met XR and some of your other medicines can affect each other. You may need to have your dose of Actoplus Met XR or certain other medicines changed.

Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist before you start a new medicine. They will tell you if it is okay to take Actoplus Met XR with other medicines.

How should I take Actoplus Met XR?

• Take Actoplus Met XR exactly as your doctor tells you to take it • Your doctor may need to change your dose of Actoplus Met XR. Do not change your Actoplus Met XR dose unless your doctor tells you to • Actoplus Met XR may be prescribed alone or with other diabetes medicines. This will depend on how well your blood sugar is controlled • Take Actoplus Met XR once a day with meals to lower your chance of an upset stomach • Take Actoplus Met XR tablets whole. Do not chew, cut, or crush the tablets. If you cannot swallow Actoplus Met XR whole, tell your doctor. You may need a different medicine. • If you take Actoplus Met XR, you may see something that looks like the Actoplus Met XR tablet in your stools. This is normal. • If you miss a dose of Actoplus Met XR, take your next dose as prescribed unless your doctor tells you differently. Do not take two doses at one time the next day • If you take too much Actoplus Met XR, call your doctor or go to the nearest hospital emergency room right away • If your body is under stress, such as from a fever, infection, accident or surgery, the dose of your diabetes medicines may need to be changed. Call your doctor right away • Stay on your diet and exercise programs and test your blood sugar regularly while taking Actoplus Met XR • Your doctor should do certain blood tests before you start and while you take Actoplus Met XR • Your doctor should also do hemoglobin A1C testing to check how well your blood sugar is controlled with Actoplus Met XR • Your doctor should check your eyes regularly while you take Actoplus Met XR

What are the possible side effects of Actoplus Met XR?

Actoplus Met XR may cause serious side effects including:

• See "What is the most important information I should know about Actoplus Met XR?" • low blood sugar (hypoglycemia). This can happen if you skip meals, if you also use another medicine that lowers blood sugar, or if you have certain medical problems. Lightheadedness, dizziness, shakiness, or hunger may happen if your blood sugar is too low. Call your doctor if low blood sugar levels are a problem for you • liver problems. Call your doctor right away if you have: • nausea or vomiting • stomach pain • unusual or unexplained tiredness • loss of appetite • dark urine • yellowing of your skin or the whites of your eyes • bladder cancer. There may be an increased chance of having bladder cancer when you take Actoplus Met XR. You should not take Actoplus Met XR if you are receiving treatment for bladder cancer. Tell your doctor right away if you have any of the following symptoms of bladder cancer: o blood or a red color in your urine o an increased need to urinate o pain while you urinate • broken bones (fractures). Usually in the hand, upper arm, or foot in women. Talk to your doctor for advice on how to keep your bones healthy • diabetic eye disease with swelling in the back of the eye (macular edema). Tell your doctor right away if you have any changes in your vision. Your doctor should check your eyes regularly • release of an egg from an ovary in a woman (ovulation) leading to pregnancy. Ovulation may happen when premenopausal women who do not have regular monthly periods take Actoplus Met XR. This can increase your chance of getting pregnant • low red blood cell count (anemia)

The most common side effects of Actoplus Met XR include:

• cold-like symptoms (upper respiratory tract infection) • swelling (edema) • diarrhea • headache • increased weight

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the side effects of Actoplus Met XR. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Actoplus Met XR?

• Store Actoplus Met XR at 68°F to 77°F (20°C to 25°C). Keep Actoplus Met XR in the original container to protect from light • Keep the Actoplus Met XR bottle tightly closed and keep tablets dry

Keep Actoplus Met XR and all medicines out of the reach of children.

General information about the safe and effective use of Actoplus Met XR

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Actoplus Met XR for a condition for which it was not prescribed. Do not give Actoplus Met XR to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about Actoplus Met XR. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Actoplus Met XR that is written for healthcare professionals. For more information, go to www.actoplusmetxr.com or call 1-877-825-3327.

What are the ingredients in Actoplus Met XR?

Active Ingredients: pioglitazone and metformin hydrochloride.

Inactive Ingredients: candelilla wax, cellulose acetate, povidone, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, hypromellose, polyethylene glycols (PEG 400, PEG 8000), sodium lauryl sulfate, titanium dioxide, and triacetin. Ink contains shellac, iron-oxide red (15 mg/1000 mg tablet strength), FD&C Blue No. 2 Lake (30 mg/1000 mg tablet strength), propylene glycol, and ammonium hydroxide.

ACTOS and Actoplus Met XR are trademarks of Takeda Pharmaceutical Company Limited registered with the U.S. Patent and Trademark Office and used under license by Takeda Pharmaceuticals America, Inc.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Distributed by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Revised: December 2016

©2009 - 2016 Takeda Pharmaceuticals America, Inc.

AMX002 R10

PRINCIPAL DISPLAY PANEL – 15 mg/1000 mg Tablet Bottle Label

30 Tablets NDC 64764-510-30

Actoplus Met XR
(pioglitazone and metformin HCl
extended-release) Tablets

15 mg/1000 mg

Each film-coated tablet contains
pioglitazone hydrochloride equivalent
to 15 mg pioglitazone and 1000 mg
metformin hydrochloride.

Dispense with Medication Guide
available in package insert or at
www.actoplusmetxr.com

Takeda logo

Rx Only

PRINCIPAL DISPLAY PANEL - 30 mg/1000 mg Tablet Bottle Label

30 Tablets NDC 64764-310-30

Actoplus Met XR
(pioglitazone and metformin HCl
extended-release) Tablets

30 mg/1000 mg

Each film-coated tablet contains
pioglitazone hydrochloride equivalent
to 30 mg pioglitazone and 1000 mg
metformin hydrochloride.

Dispense with Medication Guide
available in package insert or at
www.actoplusmetxr.com

Takeda logo

Rx Only

ACTOPLUS MET  XR
pioglitazone and metformin hydrochloride tablet, film coated, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-510
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
pioglitazone hydrochloride (pioglitazone) pioglitazone 15 mg
metformin hydrochloride (metformin) metformin hydrochloride 1000 mg
Inactive Ingredients
Ingredient Name Strength
candelilla wax  
cellulose acetate  
POVIDONE, UNSPECIFIED  
HYDROXYPROPYL CELLULOSE (1200000 MW)  
lactose monohydrate  
magnesium stearate  
HYPROMELLOSE, UNSPECIFIED  
polyethylene glycol 400  
polyethylene glycol 8000  
sodium lauryl sulfate  
titanium dioxide  
triacetin  
shellac  
propylene glycol  
ammonia  
ferric oxide red  
Product Characteristics
Color WHITE (white to off-white) Score no score
Shape ROUND Size 13mm
Flavor Imprint Code 4833X;15;1000
Contains     
Packaging
# Item Code Package Description
1 NDC:64764-510-30 30 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC
2 NDC:64764-510-60 60 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC
3 NDC:64764-510-90 90 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC
4 NDC:64764-510-07 1 BLISTER PACK in 1 CARTON
4 7 TABLET, FILM COATED, EXTENDED RELEASE in 1 BLISTER PACK
5 NDC:64764-510-33 30 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA022024 06/11/2010
ACTOPLUS MET  XR
pioglitazone and metformin hydrochloride tablet, film coated, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-310
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
pioglitazone hydrochloride (pioglitazone) pioglitazone 30 mg
metformin hydrochloride (metformin) metformin hydrochloride 1000 mg
Inactive Ingredients
Ingredient Name Strength
candelilla wax  
cellulose acetate  
POVIDONE, UNSPECIFIED  
HYDROXYPROPYL CELLULOSE (1200000 MW)  
lactose monohydrate  
magnesium stearate  
HYPROMELLOSE, UNSPECIFIED  
polyethylene glycol 400  
polyethylene glycol 8000  
sodium lauryl sulfate  
titanium dioxide  
triacetin  
shellac  
propylene glycol  
ammonia  
FD&C Blue No. 2  
Aluminum Oxide  
Product Characteristics
Color WHITE (white to off-white) Score no score
Shape ROUND Size 13mm
Flavor Imprint Code 4833X;30;1000
Contains     
Packaging
# Item Code Package Description
1 NDC:64764-310-30 30 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC
2 NDC:64764-310-60 60 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC
3 NDC:64764-310-90 90 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC
4 NDC:64764-310-07 1 BLISTER PACK in 1 CARTON
4 7 TABLET, FILM COATED, EXTENDED RELEASE in 1 BLISTER PACK
5 NDC:64764-310-33 30 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA022024 06/11/2010
Labeler - Takeda Pharmaceuticals America, Inc. (830134016)
Revised: 01/2017   Takeda Pharmaceuticals America, Inc.

Uses of Actoplus Met XR

Actoplus Met XR is a prescription medication used to treat type 2 diabetes.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Inform MD

Before taking Actoplus Met XR, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

  • are allergic to Actoplus Met XR or to any of its ingredients
  • have kidney problems
  • have liver problems
  • have heart problems
  • have or have had bladder cancer
  • have diabetic eye disease
  • are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

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