Prescription Drug Name:

METFORMIN HYDROCHLORIDE EXTENDED-RELEASE TABLETS USP, 500 mg and 750 mg, 7267, 7212, Rx only

ID:

eb42803c-ac3f-418a-a5d7-cf81e479f8b1

Code:

34391-3

DESCRIPTION


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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Metformin hydrochloride extended-release tablets USP are oral antihyperglycemic drugs 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: C4H11N5•HCl M.W. 165.63 Metformin hydrochloride is a white to off-white crystalline compound. 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. Metformin hydrochloride extended-release tablets USP contain 500 mg or 750 mg of metformin hydrochloride as the active ingredient. In addition, each tablet contains the following inactive ingredients: ethylcellulose, hypromellose, magnesium stearate and microcrystalline cellulose. The 750 mg tablet also contains ferric oxide red and ferric oxide yellow. Metformin hydrochloride extended-release tablets USP meet USP Dissolution Test 2.

INDICATIONS AND USAGE


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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


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displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Metformin hydrochloride extended-release tablets are contraindicated in patients with: Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels ≥ 1.5 mg/dL [males], ≥ 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).
Known hypersensitivity to metformin hydrochloride.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin. Metformin hydrochloride extended-release tablets 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


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displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

In a U.S. double-blind clinical study of metformin hydrochloride tablets in patients with type 2 diabetes, a total of 141 patients received metformin hydrochloride tablet therapy (up to 2550 mg per day) and 145 patients received placebo. Adverse reactions reported in greater than 5% of the metformin hydrochloride tablet patients, and that were more common in metformin hydrochloride tablet- than placebo-treated patients, are listed in Table 11.

Table 11: Most Common Adverse Reactions (> 5.0 Percent) in a Placebo-Controlled Clinical Study of Metformin Hydrochloride Tablet MonotherapyReactions that were more common in metformin hydrochloride tablet- than placebo-treated patients.
 Adverse Reaction  Metformin Hydrochloride Tablet
Monotherapy (n = 141) 		 Placebo (n
=
145
)
 % of Patients
 Diarrhea  53.2  11.7
 Nausea/Vomiting  25.5  8.3
 Flatulence  12.1  5.5
 Asthenia  9.2  5.5
 Indigestion  7.1  4.1
 Abdominal Discomfort  6.4  4.8
 Headache  5.7  4.8
Diarrhea led to discontinuation of study medication in 6% of patients treated with metformin hydrochloride tablets. Additionally, the following adverse reactions were reported in ≥ 1.0 to ≤ 5.0% of metformin hydrochloride tablet patients and were more commonly reported with metformin hydrochloride tablets than placebo: abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation. 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 tablet patients, and that were more common in metformin hydrochloride extended-release tablet- than placebo-treated patients, are listed in Table 12.
Table 12: Most Common Adverse Reactions (> 5.0 Percent) in Placebo-Controlled Studies of Metformin Hydrochloride Extended-Release TabletsReactions that were more common in metformin hydrochloride extended-release tablet- than placebo-treated patients.
   Metformin Hydrochloride Extended-Release Tablets (n
=
781
) 		  
Placebo (n = 195)
 Adverse Reaction  % of Patients
 Diarrhea  9.6  2.6
 Nausea/Vomiting  6.5  1.5
Diarrhea led to discontinuation of study medication in 0.6% of patients treated with metformin hydrochloride extended-release tablets. Additionally, the following adverse reactions were reported in > 1.0% to < 5.0% of metformin hydrochloride extended-release tablet patients and were more commonly reported with metformin hydrochloride extended-release tablets than placebo: abdominal pain, constipation, distention abdomen, dyspepsia/heartburn, flatulence, dizziness, headache, upper respiratory infection, taste disturbance.

OVERDOSAGE


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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: 114d0980-4106-4de8-aa7e-55d961c15d70
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 USP or any other pharmacologic agent. Dosage of metformin hydrochloride extended-release tablets USP must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses. The maximum recommended daily dose of metformin hydrochloride extended-release tablets USP in adults is 2000 mg. Metformin hydrochloride extended-release tablets USP should generally be given once daily with the evening meal. Metformin hydrochloride extended-release tablets USP 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 USP 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 USP, 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 USP may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone. Metformin hydrochloride extended-release tablets USP must be swallowed whole and never crushed or chewed. Occasionally, the inactive ingredients of metformin hydrochloride extended-release tablets USP will be eliminated in the feces as a soft, hydrated mass (see PATIENT INFORMATION printed below).

HOW SUPPLIED


id: dbc4bb66-b9b7-4da4-bd43-97b74473ffc3
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Metformin hydrochloride extended-release tablets USP 500 mg, are available as white to off-white oval caplets, debossed with “93” on one side and “7267” on the other side. They are available in blistercards of 30 and 31.

PATIENT INFORMATION ABOUT METFORMIN HYDROCHLORIDE EXTENDED-RELEASE TABLETS USP


id: 01788e02-a425-4aca-952c-8aeb770721bb
displayName: SPL PATIENT PACKAGE INSERT SECTION
FDA Article Code: 42230-3

Rx only 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 USP? Metformin hydrochloride extended-release tablets USP 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 USP, 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 USP help 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 USP do not cause your body to make more insulin. Because of this, when taken alone, they rarely cause hypoglycemia (low blood sugar), and usually do not cause weight gain. However, when they are 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 hydrochloride tablets 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 USP (see “What are the side effects of metformin hydrochloride extended-release tablets USP?”). Who should not take metformin hydrochloride extended-release tablets USP? Some conditions increase your chance of getting lactic acidosis, or cause other problems if you take metformin hydrochloride extended-release tablets USP. Most of the conditions listed below can increase your chance of getting lactic acidosis. Do not take metformin hydrochloride extended-release tablets USP if you: have kidney problems
have liver problems
have heart failure that is treated with medicines, such as digoxin or 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 USP 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 USP be used in children? Metformin hydrochloride extended-release tablets USP have not been studied in children. How should I take metformin hydrochloride extended-release tablets USP? 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 USP with meals. Your doctor may have you take other medicines along with metformin hydrochloride extended-release tablets USP to control your blood sugar. These medicines may include insulin shots. Taking metformin hydrochloride extended-release tablets USP 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 USP. 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 USP cause 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 USP 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 USP for a short time.
start to take other medicines or change how you take a medicine. Metformin hydrochloride extended-release tablets USP can affect how well other drugs work, and some drugs can affect how well metformin hydrochloride extended-release tablets USP work. Some medicines may cause high blood sugar. Metformin hydrochloride extended-release tablets USP must be swallowed whole and never crushed or chewed. Occasionally, the inactive ingredients of metformin hydrochloride extended-release tablets USP 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 USP work to control your diabetes. What should I avoid while taking metformin hydrochloride extended-release tablets USP? Do not drink a lot of alcoholic drinks while taking metformin hydrochloride extended-release tablets USP. 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 USP?

Lactic Acidosis.


In rare cases, metformin hydrochloride extended-release tablets USP can cause a serious side effect called lactic acidosis. This is caused by a buildup of lactic acid in your blood. This buildup can cause serious damage. Lactic acidosis caused by metformin hydrochloride extended-release tablets USP 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 hydrochloride tablets 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 USP. Your liver helps remove lactic acid from your body. Make sure you tell your doctor before you use metformin hydrochloride extended-release tablets USP if you have kidney or liver problems. You should also stop using metformin hydrochloride extended-release tablets USP 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 USP and call your doctor right away. This may be a sign of lactic acidosis or another serious side effect. Other Side Effects. Common side effects of metformin hydrochloride extended-release tablets USP 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 USP have an unpleasant metallic taste when they start taking the medicine. It lasts for a short time. Metformin hydrochloride extended-release tablets USP 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 USP 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 USP for a condition for which they were not prescribed. Do not share your medicine with other people. Manufactured In Israel By: TEVA PHARMACEUTICAL IND. LTD. Jerusalem, 91010, Israel Manufactured For: TEVA PHARMACEUTICALS USA Sellersville, PA 18960 Rev. I 10/2008

PRINCIPAL DISPLAY PANEL


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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

Metformin Hydrochloride ER Tabs, USP 500mg