Actoplus Met

Metformin and pioglitazone is a combination of two oral diabetes medicines that help control blood sugar levels.

Metformin and pioglitazone is for people with type 2 diabetes who do not use daily insulin injections. This medication is not for treating type 1 diabetes.

Metformin and pioglitazone may also be used for purposes not listed in this medication guide.

Take the missed dose as soon as you remember (be sure to take the medicine with food). Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

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

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.

• If you have an allergy to metformin, pioglitazone, or any other part of Actoplus Met.
• 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 with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with meals.
• To gain the most benefit, do not miss doses.
• Take Actoplus Met at the same time of day.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

• Store in the original container at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep lid tightly closed.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about Actoplus Met, please talk with the doctor, pharmacist, or other health care provider.
• 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.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Actoplus Met. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Actoplus Met.

Review Date: October 4, 2017

Actoplus Met tablets are a thiazolidinediones and biguanide combination product that contains two oral antidiabetic medications: pioglitazone hydrochloride and metformin hydrochloride.

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 is 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: povidone USP, microcrystalline cellulose NF, croscarmellose sodium NF, magnesium stearate NF, hypromellose 2910 USP, polyethylene glycol 8000 NF, titanium dioxide USP, and talc USP.

Actoplus Met is part of the drug class:

• Combinations of oral blood glucose lowering drugs

Serious side effects have been reported with Actoplus Met including the following:

• Congestive heart failure. Tell your healthcare provider right away if you have some or all of the following symptoms of congestive heart failure.
  • large weight gain in a short period of time
  • shortness of breath
  • swelling of the arms, hands, feet, ankles, or lower legs
  • swelling or pain in the stomach
  • waking up short of breath during the night
  • needing to sleep with extra pillows under your head in order to breathe easier while lying down
  • frequent dry cough or wheezing
  • difficulty thinking clearly or confusion
  • fast or racing heart beat
  • not able to walk or exercise as well
  • increased tiredness

• Lactic acidosis. Tell your healthcare provider right away if you have some or all of the following symptoms of congestive heart failure.
  • Extreme tiredness
  • Weakness or discomfort
  • Unusual or unexpected stomach pain
  • Decreased appetite
  • Deep and rapid breathing or shortness of breath
  • Dizziness
  • Lightheadedness
  • Fast or slow heart beat
  • Flushing of the skin
  • Muscle pain
  • Feeling cold
• Hypoglycemia (low blood sugar). Tell your healthcare provider right away if you have some or all of the following symptoms of hypoglycemia.
  • Lightheadedness
  • Dizziness
  • Shakiness
  • Hunger
  • Blurred vision
• Liver problems. Tell your healthcare provider right away if you have some or all of the following symptoms of liver problems.
  • Nausea
  • Vomiting
  • Loss of appetite
  • Pain in the upper right part of the abdomen
  • Flu-like symptoms
  • Dark urine
  • Yellowing of the skin or eyes
  • Unusual bleeding or bruising
  • Lack of energy
• Ovulation. Pioglitazone, like other thiazolidinediones, may stimulate ovulation in premenopausal women and increase the chance of pregnancy.

Do not take Actoplus Met if you:

• are allergic to Actoplus Met or to any of its ingredients
• have NYHA Class III or IV heart failure
• have kidney problems
• have metabolic acidosis

Actoplus Met contains a combination of metformin and pioglitazone, two oral diabetes medicines that help control blood sugar levels.

Actoplus Met is for people with type 2 diabetes who do not use daily insulin injections.

Actoplus Met is not for treating type 1 diabetes.