METFORMIN HYDROCHLORIDE EXTENDED-RELEASE TABLETS, USP, Rx Only

DESCRIPTION

id: d7a8b036-4aca-4708-9095-3c3cd9f5591d
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Metformin hydrochloride extended-release tablets, USP are an oral antihyperglycemic drug used in the management of type 2 diabetes.  Metformin hydrochloride (N,N-dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents. The structural formula is as shown: Metformin hydrochloride, USP is a white to off-white crystalline compound with a molecular formula of C₄H₁₁N₅•HCl and a molecular weight of 165.63. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether, and chloroform.  The pK_a of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68.  Metformin hydrochloride extended-release tablets, USP contain 500 mg or 750 mg of metformin hydrochloride as the active ingredient.  Metformin hydrochloride extended-release 500 mg tablets, USP contain the inactive ingredients hypromellose 2208, colloidal silicon dioxide, and magnesium stearate.  Metformin hydrochloride extended-release 750 mg tablets, USP contain the inactive ingredients hypromellose 2208, colloidal silicon dioxide, D&C yellow #10 aluminum lake, and magnesium stearate. 

INDICATIONS AND USAGE

id: 70abe9c3-8dfe-49cd-a452-d9b78549edc9
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Metformin hydrochloride extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

CONTRAINDICATIONS

id: acb9fc7e-1e3c-41bc-a0fa-e6c1d4551dbf
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Metformin hydrochloride extended-release tablets are contraindicated in patients with: 1. Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels greater than or equal to 1.5 mg/dL [males], greater than or equal to 1.4 mg/dL [females] or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia (see  WARNINGS  and PRECAUTIONS ).
2. Known hypersensitivity to metformin hydrochloride.
3. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.  Metformin should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function. (See also PRECAUTIONS .)

ADVERSE REACTIONS

id: 387fa485-e4f1-4980-af3b-5d288290731d
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

In worldwide clinical trials over 900 patients with type 2 diabetes have been treated with metformin hydrochloride extended-release tablets in placebo- and active-controlled studies. In placebo-controlled trials, 781 patients were administered metformin hydrochloride extended-release tablets and 195 patients received placebo. Adverse reactions reported in greater than 5% of the metformin hydrochloride extended-release tablets patients, and that were more common in metformin hydrochloride extended-release tablets – than placebo-treated patients, are listed in Table 12.

OVERDOSAGE

id: 19e5e2e5-03fe-4e6b-b932-b2c48d0c155d
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases (see WARNINGS ). 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 drug from patients in whom metformin overdosage is suspected.

DOSAGE AND ADMINISTRATION

id: a36a7acf-7a26-4f87-8748-d236d8bf49e0
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with metformin hydrochloride extended-release tablets or any other pharmacologic agent. Dosage of metformin hydrochloride extended-release tablets must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily dose. The maximum recommended daily dose of metformin hydrochloride extended-release tablets in adults is 2000 mg.  Metformin hydrochloride extended-release tablets should generally be given once daily with the evening meal. Metformin hydrochloride extended-release tablets should be started at a low dose, with gradual dose escalation, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.  During treatment initiation and dose titration (see Recommended Dosing Schedule), fasting plasma glucose should be used to determine the therapeutic response to metformin hydrochloride extended-release tablets and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of metformin hydrochloride extended-release tablets, either when used as monotherapy or in combination with sulfonylurea or insulin. Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication, and secondary failure, i.e., loss of an adequate blood glucose lowering response after an initial period of effectiveness.  Short-term administration of metformin hydrochloride extended-release tablets may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone.  Metformin hydrochloride extended-release tablets must be swallowed whole and never crushed or chewed. Occasionally, the inactive ingredients of metformin hydrochloride extended-release will be eliminated in the feces as a soft, hydrated mass. (See Patient Information printed below.)

HOW SUPPLIED

id: b435101b-fbee-46b8-b6d0-87d33c78a1ff
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Metformin hydrochloride extended-release tablets, USP are available as: 500 mg Bottles of 60 NDC 70914-002-60 Metformin hydrochloride extended-release 500 mg tablets, USP are white to off-white, capsule shaped tablets, debossed with the “ ” and “571”on one side and “500” on the other side.

PATIENT INFORMATION

id: 9b3e631c-bd45-48fc-ba3a-74231c730da2
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

METFORMIN HYDROCHLORIDE (met-FORE-min HYE-droe-KLOR-ide)
EXTENDED-RELEASE TABLETS, USP Read this information carefully before you start taking this medicine and each time you refill your prescription. There may be new information. This information does not take the place of your doctor’s advice. Ask your doctor or pharmacist if you do not understand some of this information or if you want to know more about this medicine. What are metformin hydrochloride extended-release tablets? Metformin hydrochloride extended-release tablets are used to treat type 2 diabetes. This is also known as non-insulin-dependent diabetes mellitus. People with type 2 diabetes are not able to make enough insulin or respond normally to the insulin their bodies make. When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical problems including kidney damage, amputations, and blindness. Diabetes is also closely linked to heart disease. The main goal of treating diabetes is to lower your blood sugar to a normal level. High blood sugar can be lowered by diet and exercise, by a number of medicines taken by mouth, and by insulin shots. Before you take metformin hydrochloride extended-release tablets, try to control your diabetes by exercise and weight loss. While you take your diabetes medicine, continue to exercise and follow the diet advised for your diabetes. No matter what your recommended diabetes management plan is, studies have shown that maintaining good blood sugar control can prevent or delay complications of diabetes, such as blindness. Metformin hydrochloride extended-release tablets works longer in your body and helps control your blood sugar in a number of ways. These include helping your body respond better to the insulin it makes naturally, decreasing the amount of sugar your liver makes, and decreasing the amount of sugar your intestines absorb. Metformin hydrochloride extended-release tablets do not cause your body to make more insulin. Because of this, when taken alone, it rarely causes hypoglycemia (low blood sugar), and usually does not cause weight gain. However, when taken with a sulfonylurea or with insulin, hypoglycemia is more likely to occur, as is weight gain. WARNING: A small number of people who have taken metformin have developed a serious condition called lactic acidosis. Lactic acidosis is caused by a buildup of lactic acid in the blood. This happens more often in people with kidney problems. Most people with kidney problems should not take metformin hydrochloride extended-release tablets. (See “What are the side effects of metformin hydrochloride extended-release tablets?”) Who should not take metformin hydrochloride extended-release tablets? Some conditions increase your chance of getting lactic acidosis, or cause other problems if you take this medicine. Most of the conditions listed below can increase your chance of getting lactic acidosis. Do not take metformin hydrochloride extended-release tablets if you: have kidney problems 
have liver problems 
have heart failure that is treated with medicines, such as Lanoxin® (digoxin) or Lasix® (furosemide) 
drink a lot of alcohol. This means you binge drink for short periods or drink all the time 
are seriously dehydrated (have lost a lot of water from your body) 
are going to have an x-ray procedure with injection of dyes (contrast agents) 
are going to have surgery 
develop a serious condition, such as heart attack, severe infection, or a stroke 
are 80 years or older and you have NOT had your kidney function tested Tell your doctor if you are pregnant or plan to become pregnant. Metformin hydrochloride extended-release tablets may not be right for you. Talk with your doctor about your choices. You should also discuss your choices with your doctor if you are nursing a child. Can metformin hydrochloride extended-release tablets be used in children? Metformin hydrochloride extended-release tablets have not been studied in children.  How should I take metformin hydrochloride extended-release tablets? Your doctor will tell you how much medicine to take and when to take it. You will probably start out with a low dose of the medicine. Your doctor may slowly increase your dose until your blood sugar is better controlled. You should take metformin hydrochloride extended-release tablets with meals.  Your doctor may have you take other medicines along with metformin hydrochloride extended-release tablets to control your blood sugar. These medicines may include insulin shots. Taking metformin hydrochloride extended-release tablets with insulin may help you better control your blood sugar while reducing the insulin dose.  Continue your exercise and diet program and test your blood sugar regularly while taking metformin hydrochloride extended-release tablets. Your doctor will monitor your diabetes and may perform blood tests on you from time to time to make sure your kidneys and your liver are functioning normally. There is no evidence that metformin hydrochloride extended-release tablets causes harm to the liver or kidneys. Tell your doctor if you: have an illness that causes severe vomiting, diarrhea or fever, or if you drink a much lower amount of liquid than normal. These conditions can lead to severe dehydration (loss of water in your body). You may need to stop taking metformin hydrochloride extended-release tablets for a short time. 
plan to have surgery or an x-ray procedure with injection of dye (contrast agent). You may need to stop taking metformin hydrochloride extended-release tablets for a short time. 
start to take other medicines or change how you take a medicine. Metformin hydrochloride extended-release tablets can affect how well other drugs work, and some drugs can affect how well metformin hydrochloride extended-release tablets work. Some medicines may cause high blood sugar. Metformin hydrochloride extended-release tablets must be swallowed whole and never crushed or chewed. Occasionally, the inactive ingredients of metformin hydrochloride extended-release tablets may be eliminated as a soft mass in your stool that may look like the original tablet; this is not harmful and will not affect the way metformin hydrochloride extended-release tablets work to control your diabetes.  What should I avoid while taking metformin hydrochloride extended-release tablets? Do not drink a lot of alcoholic drinks while taking metformin hydrochloride extended-release tablets.  This means you should not binge drink for short periods, and you should not drink a lot of alcohol on a regular basis. Alcohol can increase the chance of getting lactic acidosis. What are the side effects of metformin hydrochloride extended-release tablets?
Lactic Acidosis. In rare cases, metformin can cause a serious side effect called lactic acidosis. This is caused by a buildup of lactic acid in your blood. This build-up can cause serious damage. Lactic acidosis caused by metformin hydrochloride extended-release tablets is rare and has occurred mostly in people whose kidneys were not working normally. Lactic acidosis has been reported in about one in 33,000 patients taking metformin over the course of a year. Although rare, if lactic acidosis does occur, it can be fatal in up to half the people who develop it.  It is also important for your liver to be working normally when you take metformin hydrochloride extended-release tablets. Your liver helps remove lactic acid from your blood.  Make sure you tell your doctor before you use metformin hydrochloride extended-release tablets if you have kidney or liver problems. You should also stop using metformin hydrochloride extended-release tablets and call your doctor right away if you have signs of lactic acidosis. Lactic acidosis is a medical emergency that must be treated in a hospital. Signs of lactic acidosis are: feeling very weak, tired, or uncomfortable 
unusual muscle pain 
trouble breathing 
unusual or unexpected stomach discomfort 
feeling cold 
feeling dizzy or lightheaded 
suddenly developing a slow or irregular heartbeat  If your medical condition suddenly changes, stop taking metformin hydrochloride extended-release tablets and call your doctor right away. This may be a sign of lactic acidosis or another serious side effect.  Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Other Side Effects. Common side effects of metformin hydrochloride extended-release tablets include diarrhea, nausea, and upset stomach. These side effects generally go away after you take the medicine for a while. Taking your medicine with meals can help reduce these side effects. Tell your doctor if the side effects bother you a lot, last for more than a few weeks, come back after they’ve gone away, or start later in therapy. You may need a lower dose or need to stop taking the medicine for a short period or for good.  About 3 out of every 100 people who take metformin hydrochloride extended-release tablets have an unpleasant metallic taste when they start taking the medicine. It lasts for a short time.  Metformin hydrochloride extended-release tablets rarely cause hypoglycemia (low blood sugar) by themselves. However, hypoglycemia can happen if you do not eat enough, if you drink alcohol, or if you take other medicines to lower blood sugar. General advice about prescription medicines If you have questions or problems, talk with your doctor or other healthcare provider. You can ask your doctor or pharmacist for the information about metformin hydrochloride extended-release tablets that is written for healthcare professionals.  Medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. Do not use metformin hydrochloride extended-release tablets for a condition for which it was not prescribed. Do not share your medicine with other people.  Brands listed are the trademarks of their respective owners. Manufactured by:
Watson Laboratories, Inc.
Corona, CA  92880  USA Distributed by:
Hudson Scientific LLC
103 W. Main ST
Hudson, MI  49247  Revised: December 2016

Principal Display Panel

id: 6e4c69ce-0f7b-4bc3-8163-579feaa3e5de
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

NDC 70914-002-60Metformin Hydrochloride
Extended-Release
Tablets, USP 
500 mg

60 Tablets 
Rx Only