Metformin Hydrochloride Tablets, USP, Rx only

/Metformin Hydrochloride Tablets, USP, Rx only
Metformin Hydrochloride Tablets, USP, Rx only2018-09-06T09:12:40+00:00

Prescription Drug Name:

Metformin Hydrochloride Tablets, USP, Rx only

ID:

2919983f-4508-4bce-886b-0f686444fa98

Code:

34391-3

DESCRIPTION


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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Metformin hydrochloride, USP is 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, USP is freely soluble in water and 4 11 5 is practically insoluble in acetone, ether and chloroform. The pK of metformin is 12.4. The pH of a 1% a aqueous solution of metformin hydrochloride, USP is 6.68.
Metformin hydrochloride tablets USP contain 500 mg, 850 mg and 1000 mg of metformin hydrochloride, USP. Each tablet contains the inactive ingredients povidone, polyethylene glycol and magnesium stearate. In addition the coating for 500 mg, 850 mg and 1000 mg contains: lactose monohydrate, hypromellose, titanium dioxide and triacetin.

CLINICAL PHARMACOLOGY


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displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

Mechanism of Action
Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin hydrochloride decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects (except in special circumstances, see PRECAUTIONS ) 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.

Pharmacokinetics
Absorption and Bioavailability
The absolute bioavailability of a metformin hydrochloride 500 mg tablet given under fasting conditions is approximately 50-60%. Studies using single oral doses of metformin hydrochloride tablets, USP of 500 mg to 1500 mg, and 850 mg to 2550 mg, indicate that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption rather than an alteration in elimination. Food decreases the extent of and slightly delays the absorption of metformin, as shown by approximately a 40% lower mean peak plasma concentration (C), a 25% lower area under the plasma concentration versus time curve max (AUC), and a 35 minute prolongation of time to peak plasma concentration (T ) following administration max of a single 850 mg tablet of metformin with food, compared to the same tablet strength administered fasting. The clinical relevance of these decreases is unknown.

Distribution
The apparent volume of distribution (V/F) of metformin following single oral doses of 850 mg averaged 654 ± 358 L. Metformin is negligibly bound to plasma proteins in contrast to sulfonylureas which are more than 90% protein bound. Metformin partitions into erythrocytes, most likely as a function of time. At usual clinical doses and dosing schedules of metformin hydrochloride tablets, USP steady state plasma concentrations of metformin are reached within 24-48 hours and are generally < 1 μg/mL. During controlled clinical trials of metformin, maximum metformin plasma levels did not exceed 5 μg/mL, even at maximum doses.

Metabolism and Elimination
Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. Renal clearance (see Table 1) is approximately 3.5 times greater than creatinine clearance which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.

Special Populations
Patients with Type 2 Diabetes
In the presence of normal renal function, there are no differences between single or multiple dose pharmacokinetics of metformin between patients with type 2 diabetes and normal subjects (see Table 1),nor is there any accumulation of metformin in either group at usual clinical doses.

Renal Insufficiency
In patients with decreased renal function (based on measured creatinine clearance), the plasma and blood half-life of metformin is prolonged and the renal clearance is decreased in proportion to the decrease in creatinine clearance (see Table 1; also see WARNINGS ).

Hepatic Insufficiency
No pharmacokinetic studies of Metformin have been conducted in patients with hepatic insufficiency.

Geriatrics
Limited data from controlled pharmacokinetic studies of metformin in healthy elderly subjects suggest that total plasma clearance of metformin is decreased, the half-life is prolonged, and C is increased, max compared to healthy young subjects. From these data, it appears that the change in metformin pharmacokinetics with aging is primarily accounted for by a change in renal function (see Table 1).
Metformin treatment should not be initiated in patients ³ 80 years of age unless measurement of
creatinine clearance demonstrates that renal function is not reduced. (See  WARNINGS and
DOSAGE AND ADMINISTRATION
)

a-All doses given fasting except the first 18 doses of the multiple dose studies;
b-Peak plasma concentration;
c-Time to peak plasma concentration;
d-Combined results (average means) of five studies: mean age 32 years (range 23-59 yrs).
e-Kinetic study done following dose 19, given fasting.
f-Elderly subjects, mean age 71 years (range 65-81 years).
g-CL = creatinine clearance normalized to body surface area of 1.73 m2.

Pediatrics
After administration of a single oral metformin hydrochloride 500 mg tablet with food, geometric mean metformin C and AUC differed less than 5% between pediatric type 2 diabetic patients (12 to 16 years of max age) and gender- and weight-matched healthy adults (20 to 45 years of age), all with normal renal function.

Gender
Metformin pharmacokinetic parameters did not differ significantly between normal subjects and patients with type 2 diabetes when analyzed according to gender (males = 19, females = 16). Similarly, in controlled clinical studies in patients with type 2 diabetes, the antihyperglycemic effect of metformin hydrochloride tablets, USP was comparable in males and females.

Race
No studies of metformin pharmacokinetic parameters according to race have been performed. In controlled clinical studies of metformin hydrochloride tablets, USP in patients with type 2 diabetes, the antihyperglycemic effect was comparable in whites (n=249), blacks (n=51) and hispanics (n=24).

INDICATIONS & USAGE


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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Metformin hydrochloride tablets, USP are indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 2 diabetes mellitus.

CONTRAINDICATIONS


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displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Metformin hydrochloride tablets are contraindicated in patients with: 1. 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 ascardiovascular collapse (shock), acute myocardial infarction, and septicemia (see  WARNINGS and PRECAUTIONS ). 2. Known hypersensitivity to metformin hydrochloride tablets, USP. 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. )

WARNINGS


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displayName: WARNINGS SECTION
FDA Article Code: 34071-1

Lactic Acidosis:

Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels > 5 μg/mL are generally found.

The reported incidence of lactic acidosis in patients receiving metformin hydrochloride tablets, USP is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient’s age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin hydrochloride tablets, USP treatment should not be initiated in patients 80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking metformin hydrochloride tablets, USP since alcohol potentiates the effects of metformin hydrochloride tablets, USP on lactate metabolism. In addition, metformin should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS).The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence and nonspecific abdominal distress. There may be associated hypothermia, hypotension and resistant bradyarrhythmias with more marked acidosis. The patient and the patient’s physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). Metformin hydrochloride tablets, USP should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of metformin, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity or technical problems in sample handling. (See also PRECAUTIONS.) Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride tablets, USP are dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin.

Such management often results in prompt reversal of symptoms and recovery. (See also CONTRAINDICATIONS and 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 in patients with type 2 diabetes, a total of 141 patients received metformin therapy (up to 2550 mg per day) and 145 patients received placebo. Adverse reactions reported in greater than 5% of the metformin patients, and that were more common in metformin – than placebo-treated patients, are listed in Table 7.

* Reactions that were more common in metformin- than placebo-treated patients. Diarrhea led to discontinuation of study medication in 6% of patients treated with metformin. Additionally, the following adverse reactions were reported in ≥1.0 – ≤5.0% of metformin patients and were more commonly reported with metformin than placebo: abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation. Pediatric Patients In clinical trials with metformin hydrochloride tablets, USP in pediatric patients with type 2 diabetes, the profile of adverse reactions was similar to that observed in adults.

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 & ADMINISTRATION


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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 or any other pharmacologic agent. Dosage of metformin 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 tablets, USP is 2550 mg in adults and 2000 mg in pediatric patients (10-16 years of age). Metformin should be given in divided doses with meals and 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 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 tablets, USP either when used as monotherapy or in
combination with sulfonylureas 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 may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone. Recommended Dosing Schedule Adults— In general, clinically significant responses are not seen at doses below 1500 mg per day. However, a lower recommended starting dose and gradually increased dosage is advised to minimize gastrointestinal symptoms. The usual starting dose of metformin hydrochloride tablets, USP is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. Patients can also be titrated from 500 mg twice a day to 850 mg twice a day after 2 weeks. For those patients requiring additional glycemic control, metformin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals. Pediatrics—The usual starting dose of metformin hydrochloride tablets, USP is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses. Transfer from Other Antidiabetic Therapy When transferring patients from standard oral hypoglycemic agents other than chlorpropamide to metformin, no transition period generally is necessary. When transferring patients from chlorpropamide, care should be exercised during the first two weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia. Concomitant Metformin Hydrochloride Tablets, USP and Oral Sulfonylurea Therapy in Adult Patients If patients have not responded to four weeks of the maximum dose of metformin hydrochloride tablets, USP monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing metformin hydrochloride tablets, USP at the maximum dose, even if prior primary or secondary failure to a sulfonylurea has occurred. Clinical and pharmacokinetic drug-drug interaction data are currently available only for metformin plus glyburide (glibenclamide). With concomitant metformin hydrochloride tablets, USP and sulfonylurea therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. In a clinical trial of patients with type 2 diabetes and prior failure on glyburide, patients started on metformin 500 mg and glyburide 20 mg were titrated to 1000/20 mg, 1500/20 mg, 2000/20 mg or 2500/20 mg of metformin and glyburide, respectively, to reach the goal of glycemic control as measured by FPG, HbA1c and plasma glucose response (see CLINICAL  PHARMACOLOGY: Clinical Studies ). However, attempts should be made to identify the minimum effective dose of each drug to achieve this goal. With concomitant metformin hydrochloride tablets, USP and sulfonylurea therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken. (See Package Insert of the respective sulfonylurea.) If patients have not satisfactorily responded to one to three months of concomitant therapy with the maximum dose of metformin and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without metformin hydrochloride tablets, USP. Concomitant Metformin Hydrochloride Tablets, USP and Insulin Therapy in Adult Patients The current insulin dose should be continued upon initiation of metformin hydrochloride tablets, USP therapy. Metformin hydrochloride tablets, USP therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of metformin hydrochloride tablets, USP should be increased by 500 mg after approximately 1 week and by 500 mg every week thereafter until adequate glycemic control is achieved. The maximum recommended daily dose is 2500 mg for metformin hydrochloride tablets, USP. It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and metformin hydrochloride tablets, USP. Further adjustment should be individualized based on glucose-lowering response. Specific Patient Populations Metformin is not recommended for use in pregnancy. Metformin hydrochloride tablets, USP are not recommended in patients below the age of 10 years. The initial and maintenance dosing of metformin hydrochloride tablets, USP should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of metformin hydrochloride tablets, USP. Monitoring of renal function is necessary to aid in prevention of lactic acidosis, particularly in the elderly. (See WARNINGS. )

HOW SUPPLIED


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displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Product: 70786-0435 NDC: 70786-0435-2 60 TABLET in a BOTTLE NDC: 70786-0435-3 90 TABLET in a BOTTLE

CLINICAL STUDIES


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displayName: CLINICAL STUDIES SECTION
FDA Article Code: 34092-7

In a double-blind placebo-controlled, multicenter U.S. clinical trial involving obese patients with type 2 diabetes whose hyperglycemia was not adequately controlled with dietary management alone (baseline fasting plasma glucose [FPG] of approximately 240 mg/dL), treatment with metformin hydrochloride tablets, USP (up to 2550 mg/day) for 29 weeks resulted in significant mean net reductions in fasting and postprandial plasma glucose (PPG) and hemoglobin A1c (HbA1c ) of 59 mg/dL, 83 mg/dL, and 1.8%, respectively, compared to placebo group (see Table 2).

* All patients on diet therapy at Baseline ** Not statistically significant A 29-week, double-blind, placebo-controlled study of metformin and glyburide, alone and in combination, was conducted in obese patients with type 2 diabetes patients who had failed to achieve adequate glycemic control while on maximum doses of glyburide (baseline FPG of approximately 250 mg/dL) (see Table 3). Patients randomized to the combination arm started therapy with metformin hydrochloride 500 mg and glyburide 20 mg. At the end of each week of the first four weeks of the trial, these patients had their dosages of metformin hydrochloride increased by 500 mg if they had failed to reach target fasting plasma glucose. After week four, such dosage adjustments were made monthly, although no patient was allowed to exceed metformin hydrochloride 2500 mg. Patients in the metformin hydrochloride only arm (metformin plus placebo) followed the same titration schedule. At the end of the trial, approximately 70% of the patients in the combination group were taking metformin hydrochloride 2000 mg/glyburide 20 mg or metformin hydrochloride 2500 mg/glyburide 20 mg. Patients randomized to continue on glyburide experienced worsening of glycemic control, with mean increases in FPG, PPG and HbA1c of 14 mg/dL, 3 mg/dL and 0.2%, respectively. In contrast, those randomized to metformin (up to 2500 mg/day) experienced a slight improvement, with mean reductions in FPG, PPG and HbA1c of 1 mg/dL, 6 mg/dL and 0.4%, respectively. The combination of metformin and glyburide was effective in reducing FPG, PPG and HbA1c  levels by 63 mg/dL, 65 mg/dL, and 1.7%, respectively. Compared to results of glyburide treatment 1c alone, the net differences with combination treatment were -77 mg/dL, – 68 mg/dL and -1.9%, respectively (see Table 3). * All patients on glyburide, 20 mg/day, at Baseline ** Not statistically significant The magnitude of the decline in fasting blood glucose concentration following the institution of metformin hydrochloride tablets, USP therapy is proportional to the level of fasting hyperglycemia. Patients with type 2 diabetes with higher fasting glucose concentrations experienced greater declines in plasma glucose and glycosylated hemoglobin. In clinical studies, metformin, alone or in combination with a sulfonylurea, lowered mean fasting serum triglycerides, total cholesterol and LDL cholesterol levels and had no adverse effects on other lipid levels (see Table 4).

In contrast to sulfonylureas, body weight of individuals on metformin tended to remain stable or even decrease somewhat (see Tables 2 and 3). A 24-week, double blind, placebo-controlled study of metformin hydrochloride tablets, USP plus insulin versus insulin plus placebo was conducted in patients with type 2 diabetes who failed to achieve adequate glycemic control on insulin alone (see Table 5). Patients randomized to receive metformin hydrochloride plus insulin achieved a reduction in HbA of 2.10%, compared to a 1.56% reduction in HbA achieved by insulin plus placebo. The improvement in glycemic control was achieved at the final study visit with 16% less insulin, 93.0 U/day vs 110.6 U/day, metformin hydrochloride tablets, USP plus insulin versus insulin plus placebo, respectively, p=0.04.

a Statistically significant using analysis of covariance with baseline as covariate (p=0.04) Not significant using analysis of variance (values shown in table) b Statistically significant for insulin (p=0.04) A second double-blind, placebo-controlled study (n=51), with 16 weeks of randomized treatment, demonstrated that in patients with type 2 diabetes controlled on insulin for 8 weeks with an average HbA1c of 7.46 ± 0.97%, the addition of metformin hydrochloride tablets, USP maintained similar glycemic control (HbA1c 7.15 ± 0.61 versus 6.97 ± 0.62 for metformin hydrochloride tablets, USP plus insulin and placebo plus insulin, respectively) with 19% less insulin versus baseline (reduction of 23.68 ± 30.22 versus an increase of 0.43 ± 25.20 units for metformin hydrochloride tablets, USP plus insulin and placebo plus insulin, p<0.01). In addition, this study demonstrated that the combination of metformin hydrochloride tablets, USP plus insulin resulted in reduction in body weight of 3.11 ± 4.30 lbs, compared to an increase of 1.30 ± 6.08 lbs for placebo plus insulin, p=0.01.

Pediatric Clinical Studies In a double-blind, placebo-controlled study in pediatric patients aged 10 to 16 years with type 2 diabetes (mean FPG 182.2 mg/dL), treatment with metformin hydrochloride tablets, USP (up to 2000 mg/day) for up to 16 weeks (mean duration of treatment 11 weeks) resulted in a significant mean net reduction in FPG of 64.3 mg/dL, compared with placebo (see Table 6). a Pediatric patients mean age 13.8 years (range 10-16 years) * All patients on diet therapy at Baseline ** Not statistically significant

SPL PATIENT PACKAGE INSERT


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FDA Article Code: 42230-3

METFORMIN HYDROCHLORIDE 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 is metformin? Metformin is 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, 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 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 does 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, 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. (See “What are the side effects of metformin?”) Who should not take metformin? Some conditions increase your chance of getting lactic acidosis, or cause other problems if you take metformin. Most of the conditions listed below can increase your chance of getting lactic acidosis. Do not take metformin 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 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 tablets, USP be used in children? Metformin hydrochloride tablets, USP has been shown to effectively lower glucose levels in children (ages 10 to 16 years) with type 2 diabetes. Metformin hydrochloride tablets, USP have not been studied in children younger than 10 years old. Metformin hydrochloride tablets, USP have not been studied in combination with other oral glucose-control medicines in children. If you have any questions about the use of metformin hydrochloride tablets, USP in children, talk with your doctor or healthcare provider. How should I take metformin hydrochloride 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 with meals. Your doctor may have you take other medicines along with metformin to control your blood sugar. These medicines may include insulin shots. Taking metformin hydrochloride 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. 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 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 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 tablets for a short time. • start to take other medicines or change how you take a medicine. Metformin can affect how well other drugs work, and some drugs can affect how well metformin works. Some medicines may cause high blood sugar. What should I avoid while taking metformin hydrochloride tablets, USP? Do not drink a lot of alcoholic drinks while taking metformin. 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?
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 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. Your liver helps remove lactic acid from your blood. Make sure you tell your doctor before you use metformin if you have kidney or liver problems. You should also stop using metformin 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 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 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 have an unpleasant metallic taste when they start taking the medicine. It lasts for a short time. Metformin 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 that is written for health care professionals. Medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. Do not use metformin for a condition for which it was not prescribed. Do not share your medicine with other people.

Manufactured by: Sun Pharmaceutical Ind. Ltd. Halol-Baroda Highway, Halol-389 350, Gujarat, India. Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 C.S. No: 5249T35 Iss. 10/14

METFORMIN HCL 850MG TAB 60EA


id: 7e1f1e28-37d9-4809-bc02-cc6fcbece368
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4