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Metformin
Metformin ER 500 mg · Tablet, Extended Release
Overview
Active ingredients
Source: NDC DirectoryForms, strengths and routes
Source: NDC DirectoryPharmacologic classes are listed in the class section below.
Pharmacologic class
Source: NDC Directory| Class | Type | Browse |
|---|---|---|
| Biguanide [EPC] | EPC | All 47 members |
| Biguanides [CS] | CS | All 47 members |
Regulatory status
Source: Drugs@FDANDC Directory| Product | Trade name | Form | Strength | Ingredient | Status | TE | Flags |
|---|---|---|---|---|---|---|---|
| 209313-001 | METFORMIN HYDROCHLORIDE | TABLET, EXTENDED RELEASE | METFORMIN HYDROCHLORIDE | Prescription | AB1 | ||
| 209313-002 | METFORMIN HYDROCHLORIDE | TABLET, EXTENDED RELEASE | METFORMIN HYDROCHLORIDE | Prescription | AB |
Therapeutic equivalence
Source: Orange BookWhat this rating means: Therapeutically equivalent — bioequivalence demonstrated by in vivo or in vitro testing
Codes beginning with “A” indicate products the FDA considers therapeutically equivalent. Codes beginning with “B” indicate bioequivalence has not been established. See methodology.
Approval history
Source: Drugs@FDA| Type | No. | Action | Status | Date | Review |
|---|---|---|---|---|---|
| Supplement | 32 | Labeling | Approved | August 11, 2026 | Standard |
| Supplement | 11 | Labeling | Approved | July 27, 2026 | Standard |
| Supplement | 1 | Labeling | Approved | January 14, 2019 | Standard |
| Original application | 1 | Approved | March 16, 2018 | Standard |
Prescribing information
Source: openFDA Drug LabelingReproduced verbatim from the Structured Product Labeling submitted to the FDA (effective 20260430). This is the manufacturer's labelling text, not a summary and not advice.
Boxed Warning
openFDA Drug LabelingWARNING: LACTIC ACIDOSIS WARNING: LACTIC ACIDOSIS See full prescribing information for complete boxed warning. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL. ( 5.1 ) Risk factors include renal impairment, concomitant use of certain drugs, age >65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, hepatic impairment, and mitochondrial diseases. Steps to reduce the risk of and manage metformin- associated lactic acidosis in these high risk groups are provided in the Full Prescribing Information. ( 5.1 ) If lactic acidosis is suspected, discontinue metformin hydrochloride extended-release tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended. ( 5.1 ) Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin- associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin- associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL [ see Warnings and Precautions (5.1) ] . Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, hepatic impairment, and and mitochondrial diseases [see Warnings and Precautions (5.1) ] . Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided [see Dosage and Administration (2.2) , Contraindications (4) , Warnings and Precautions (5.1) ] . If metformin-associated lactic acidosis is suspected, immediately discontinue metformin hydrochloride extended-release tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see Warnings and Precautions (5.1) ] .
Recent Major Changes
openFDA Drug LabelingIndications and Usage ( 1 ) 02/2026
Indications and Usage
openFDA Drug Labeling1 INDICATIONS AND USAGE Metformin hydrochloride extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. Metformin hydrochloride extended-release tablets are biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. ( 1 )
Dosage and Administration
openFDA Drug LabelingDOSAGE & ADMINISTRATION 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 3 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.) 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 extended-release tablets, USP is 500 mg once daily with the evening meal. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved on metformin hydrochloride extended-release tablets, USP 2000 mg once daily, a trial of metformin hydrochloride extended-release tablets, USP 1000 mg twice daily should be considered. (See CLINICAL PHARMACOLOGY : Clinical Studies .) In a randomized trial, patients currently treated with metformin hydrochloride tablets were switched to metformin hydrochloride extended-release tablets. Results of this trial suggest that patients receiving metformin hydrochloride tablets treatment may be safely switched to metformin hydrochloride extended-release tablets once daily at the same total daily dose, up to 2000 mg once daily. Following a switch from metformin hydrochloride tablets to metformin hydrochloride extended-release tablets, glycemic control should be closely monitored and dosage adjustments made accordingly (see CLINICAL PHARMACOLOGY : Clinical Studies ). Pediatrics Safety and effectiveness of metformin hydrochloride extended-release tablets, USP in pediatric patients have not been established. Recommendations for Use in Renal Impairment Assess renal functio …
Dosage Forms and Strengths
openFDA Drug Labeling3 DOSAGE FORMS AND STRENGTHS Metformin hydrochloride extended-release tablets, USP are available as: • Extended-release tablets: 500 mg white to off-white uncoated, modified capsule shaped tablets debossed with "G7" on one side and plain on other side. • Extended-release tablets: 750 mg white to off white uncoated, modified capsule shaped tablets debossed with "G8" on one side and plain on other side. • Metformin Hydrochloride Extended-Release Tablets: 500 mg and 750 mg ( 3 )
Contraindications
openFDA Drug Labeling4 CONTRAINDICATIONS Metformin hydrochloride extended-release tablets are contraindicated in patients with: • Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) [see Warnings and Precautions (5.1) ]. • Hypersensitivity to metformin. • Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. • Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) ( 4 , 5.1 ) • Hypersensitivity to metformin ( 4 ) • Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. ( 4 )
Warnings and Cautions
openFDA Drug Labeling5 WARNINGS AND PRECAUTIONS Lactic Acidosis: See boxed warning . ( 5.1 ) Vitamin B 12 Deficiency: Metformin may lower vitamin B 12 levels. Measure hematological parameters annually and vitamin B 12 at 2 to 3 year intervals and manage any abnormalities. ( 5.2 ) Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Increased risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. Lower dose of insulin or insulin secretagogue may be required. ( 5.3 ) 5.1 Lactic Acidosis There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin- associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate: pyruvate ratio; metformin plasma levels were generally >5 mcg/mL. Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of metformin hydrochloride extended-release tablets. In metformin hydrochloride extended-release tablets treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin HCl is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions). Hemodialysis has often resulted in reversal of symptoms and recovery. Educate patients and their families about the symptoms of lactic acidosis and, if these symptoms occur, instruct them to discontinue metformin hydrochloride extended-release tablets and report these symptoms to their healthcare provider. For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below: Renal impairment —The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment. The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney. Clinical recommendations based upon the patient's renal function include [see Dosage and Administration (2.2) , Clinical Pharmacology (12.3) ] : o Before initiating metformin hydrochloride extended-release tablets, obtain an estimated glomerular filtration rate (eGFR). o Metformin hydrochloride extended-release tablets are contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 [see Contraindications (4) ] . o Initiation of metformin hydrochloride extended-release tablets is not recommended in patients with eGFR between 30 to 45 mL/min/1.73 m 2 . o Obtain an eGFR at least annually in all patients taking metformin hydrochloride extended-release tablets. In patients at risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently. o In patients taking metformin hydrochloride extended-release tablets whose eGFR falls below 45 mL/min/1.73 m 2 , assess the benefit and risk of continuing therapy. Drug interactions — The concomitant use of metformin hydrochloride extended-release tablets with specific drugs may increase the risk of metformin-associated lactic acidosis: those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance, or increase metformin accumulation [see Drug Interactions (7) ] …
Warnings
openFDA Drug LabelingWARNINGS LACTIC ACIDOSIS: Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension and resistant bradyarrhythmias. The onset of metformin associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin associated lactic acidosis was characterized by elevated blood lactate levels(>5 mmol/Liter), anion gap acidosis (without evidenceof ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL (see Error! Hyperlink reference not valid.). Risk factors for metformin associated lactic acidosis include renal impairment, concamitent use of certain drugs (e.g carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided (see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , AND Error! Hyperlink reference not valid. ). If metformin associated lactic acidosis is suspected, immediately discontinue metformin hydrochloride extend release tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended (see Error! Hyperlink reference not valid. ).
Adverse Reactions
openFDA Drug Labeling6 ADVERSE REACTIONS Common adverse reactions are diarrhea, nausea/vomiting, abdominal pain, constipation, abdomen distention, dyspepsia/heartburn, flatulence, dizziness, headache, upper respiratory infection, taste disturbance. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ingenus Pharmaceuticals, LLC Toll-Free at 1-877-748-1970 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following adverse reactions are also discussed elsewhere in the labeling: Lactic Acidosis [ see Boxed Warning and Warnings and Precautions (5.1) ] Vitamin B 12 Deficiency [ see Warnings and Precautions (5.2) ] Hypoglycemia [ see Warnings and Precautions (5.3) ] 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In placebo-controlled trials, 781 patients were administered metformin HCl extended-release tablets. Adverse reactions reported in greater than 5% of the patients treated with metformin HCl extended-release tablets and that were more common than in placebo-treated patients are listed in Table 1. Diarrhea led to the discontinuation of metformin HCl extended-release tablets in 0.6% of patients. Additionally, the following adverse reactions were reported in 1.0% to 5.0% of patients treated with metformin HCl extended-release tablets and were more commonly reported than in placebo-treated patients: abdominal pain, constipation, abdomen distention, dyspepsia/heartburn, flatulence, dizziness, headache, upper respiratory infection, taste disturbance. Laboratory Tests Vitamin B 12 Concentrations In clinical trials of 29-week duration with metformin HCl tablets, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of patients. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of metformin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cholestatic, hepatocellular, and mixed hepatocellular liver injury have been reported with postmarketing use of metformin.
6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In placebo-controlled trials, 781 patients were administered metformin HCl extended-release tablets. Adverse reactions reported in greater than 5% of the patients treated with metformin HCl extended-release tablets and that were more common than in placebo-treated patients are listed in Table 1. Diarrhea led to the discontinuation of metformin HCl extended-release tablets in 0.6% of patients. Additionally, the following adverse reactions were reported in 1.0% to 5.0% of patients treated with metformin HCl extended-release tablets and were more commonly reported than in placebo-treated patients: abdominal pain, constipation, abdomen distention, dyspepsia/heartburn, flatulence, dizziness, headache, upper respiratory infection, taste disturbance. Laboratory Tests Vitamin B 12 Concentrations In clinical trials of 29-week duration with metformin HCl tablets, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of patients.
Drug Interactions
openFDA Drug Labeling7 DRUG INTERACTIONS Table 2 presents clinically significant drug interactions with metformin hydrochloride extended-release tablets. Table 2: Clinically Significant Drug Interactions with Metformin Hydrochloride Extended-Release Tablets Carbonic Anhydrase Inhibitors Clinical Impact: Carbonic anhydrase inhibitors frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with metformin hydrochloride extended-release tablets may increase the risk for lactic acidosis. Intervention: Consider more frequent monitoring of these patients. Examples: Topiramate, zonisamide, acetazolamide or dichlorphenamide. Drugs that Reduce Metformin Hydrochloride Extended-Release Tablets Clearance Clinical Impact: Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology (12.3) ]. Intervention: Consider the benefits and risks of concomitant use with metformin hydrochloride extended-release tablets. Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine. Alcohol Clinical Impact: Alcohol is known to potentiate the effect of metformin on lactate metabolism. Intervention: Warn patients against excessive alcohol intake while receiving metformin hydrochloride extended-release tablets. Insulin Secretagogues or Insulin Clinical Impact: Coadministration of metformin hydrochloride extended-release tablets with an insulin secretagogue (e.g., sulfonylurea) or insulin may increase the risk of hypoglycemia. Intervention: Patients receiving an insulin secretagogue or insulin may require lower doses of the insulin secretagogue or insulin. Drugs Affecting Glycemic Control Clinical Impact: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. Intervention: When such drugs are administered to a patient receiving metformin hydrochloride extended-release tablets, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin hydrochloride extended-release tablets, observe the patient closely for hypoglycemia. Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. • Carbonic anhydrase inhibitors may increase risk of lactic acidosis. Consider more frequent monitoring ( 7 ) • Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin. Consider the benefits and risks of concomitant use ( 7 ) • Alcohol can potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake ( 7 )
Use in Specific Populations
openFDA Drug Labeling8 USE IN SPECIFIC POPULATIONS N/A • Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy. ( 8.3 ) • Geriatric Use: Assess renal function more frequently. ( 8.5 ) • Hepatic Impairment: Avoid use in patients with hepatic impairment. ( 8.7 ) 8.1 Pregnancy Risk Summary Limited data with metformin hydrochloride extended-release tablets in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk [see Data ]. There are risks to the mother and fetus associated with poorly controlled diabetes mellitus in pregnancy [see Clinical Considerations ]. No adverse developmental effects were observed when metformin was administered to pregnant Sprague Dawley rats and rabbits during the period of organogenesis at doses up to 2- and 5-times, respectively, a 2,550 mg clinical dose, based on body surface area [ see Data ]. The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes mellitus with an HbA1C >7 and has been reported to be as high as 20 to 25% in women with a HbA1C >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly-controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications. Poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Data Human Data Published data from post-marketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy. However, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Animal Data Metformin hydrochloride did not adversely affect development outcomes when administered to pregnant rats and rabbits at doses up to 600 mg/kg/day. This represents an exposure of about 2 and 5 times a 2,550 mg clinical dose based on body surface area comparisons for rats and rabbits, respectively. Determination of fetal concentrations demonstrated a partial placental barrier to metformin. 8.2 Lactation Risk Summary Limited published studies report that metformin is present in human milk [see Data ]. However, there is insufficient information to determine the effects of metformin on the breastfed infant and no available information on the effects of metformin on milk production. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for metformin hydrochloride extended-release tablets and any potential adverse effects on the breastfed child from metformin hydrochloride extended-release tablets or from the underlying maternal condition. Data Published clinical lactation studies report that metformin is present in human milk which resulted in infant doses approximately 0.11% to 1% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 0.13 and 1. However, the studies were not designed to definitely establish the risk of use of metformin during lactation because of small sample size and limited adverse event data collected in infants. 8.3 Females and Males of Reproductive Potential Discuss the potential for unintended pregnancy with premenopausal women as therapy with metformin hydroch …
Mechanism of Action
openFDA Drug Labeling12.1 Mechanism of Action Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.
Description
openFDA Drug LabelingDESCRIPTION Metformin Hydrochloride Extended-Release Tablets, USP Metformin hydrochloride extended-release tablets, USP are oral antihyperglycemic drugs used in the management of type 2 diabetes. Metformin hydrochloride, USP (N,Ndimethyl- monohydrochloride,Imidodicarbonimidic diamide) 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 or almost white, crystalline powder with a molecular formula of C4H11N5•HCl and a molecular weight of 165.62. Metformin hydrochloride is freely soluble in water, slightly soluble in alcohol, practically insoluble in acetone and in Methylene chloride. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.35. Metformin hydrochloride extended-release tablets, USP contain 500 mg or 750 mg of metformin hydrochloride as the active ingredient. Metformin hydrochloride extended-release tablets, USP 500 mg and 750 mg tablets contain the inactive ingredients hypromellose, magnesium stearate, and polyvinyl pyrrolidone. Dissolution Method: Test 10 System Components and Performance - Metformin hydrochloride extended-release tablets, USP comprises a dual hydrophilic polymer matrix system. Metformin hydrochloride, USP is combined with a drug release controlling polymer to form an "inner" phase, which is then incorporated as discrete particles into an "external" phase of a second polymer. After administration, fluid from the gastrointestinal (GI) tract enters the tablet, causing the polymers to hydrate and swell. Drug is released slowly from the dosage form by a process of diffusion through the gel matrix that is essentially independent of pH. The hydrated polymer system is not rigid and is expected to be broken up by normal peristalsis in the GI tract. The biologically inert components of the tablet may occasionally remain intact during GI transit and will be eliminated in the feces as a soft, hydrated mass. DESCRIPTION
Overdosage
openFDA Drug Labeling10 OVERDOSAGE In the event of an overdose with metformin hydrochloride extended-release tablets, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. 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 has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases [see Warnings and Precautions (5.1) ]. 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.
How Supplied / Storage and Handling
openFDA Drug Labeling16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Metformin hydrochloride extended-release tablets are supplied as oval biconvex-shaped, film-coated extended-release tablets containing 500 mg or 1,000 mg of metformin hydrochloride. NDC 50742-633: 500 mg extended-release, white or off-white tablets imprinted with “NL2” on one side: bottles of 60, 90 and 1,000. NDC 50742-633-60 – 500 mg oval biconvex-shaped tablets supplied in bottles containing 60 tablets. NDC 50742-633-90 – 500 mg oval biconvex-shaped tablets supplied in bottles containing 90 tablets. NDC 50742-633-10 – 500 mg oval biconvex-shaped tablets supplied in bottles containing 1,000 tablets. NDC 50742-634: 1000 mg extended-release, white or off-white tablets imprinted with “NL1” on one side: bottles of 30, 60 and 1,000. NDC 50742-634-30 – 1,000 mg oval biconvex-shaped tablets supplied in bottles containing 30 tablets. NDC 50742-634-60 – 1,000 mg oval biconvex-shaped tablets supplied in bottles containing 60 tablets. NDC 50742-634-10 – 1,000 mg oval biconvex-shaped tablets supplied in bottles containing 1,000 tablets. 16.2 Storage Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Avoid excessive heat and humidity. Keep tightly closed (protect from moisture). Protect from light.
16.1 How Supplied Metformin hydrochloride extended-release tablets are supplied as oval biconvex-shaped, film-coated extended-release tablets containing 500 mg or 1,000 mg of metformin hydrochloride. NDC 50742-633: 500 mg extended-release, white or off-white tablets imprinted with “NL2” on one side: bottles of 60, 90 and 1,000. NDC 50742-633-60 – 500 mg oval biconvex-shaped tablets supplied in bottles containing 60 tablets. NDC 50742-633-90 – 500 mg oval biconvex-shaped tablets supplied in bottles containing 90 tablets. NDC 50742-633-10 – 500 mg oval biconvex-shaped tablets supplied in bottles containing 1,000 tablets. NDC 50742-634: 1000 mg extended-release, white or off-white tablets imprinted with “NL1” on one side: bottles of 30, 60 and 1,000. NDC 50742-634-30 – 1,000 mg oval biconvex-shaped tablets supplied in bottles containing 30 tablets. NDC 50742-634-60 – 1,000 mg oval biconvex-shaped tablets supplied in bottles containing 60 tablets. NDC 50742-634-10 – 1,000 mg oval biconvex-shaped tablets supplied in bottles containing 1,000 tablets.
Adverse event reports
Source: openFDA FAERSAttributed to this product's most-reported active ingredient: METFORMIN HYDROCHLORIDE. Combination products with more than six active ingredients are not attributed, because a report count summed across a long ingredient list measures the list, not the medicine.
Recalls
Source: FDA Enforcement| Classification | Reported | Firm | Reason | Status |
|---|---|---|---|---|
| Class II | July 22, 2020 | Granules Pharmaceuticals Inc | CGMP Deviations: FDA analysis detected N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level | Ongoing |
Packaging and NDCs
Source: NDC Directory| Package NDC | Product NDC | Labeler | Description | Marketing start |
|---|---|---|---|---|
| 50090-6516-0 | 50090-6516 | A-S Medication Solutions | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (50090-6516-0) | June 2, 2023 |
| 50090-7372-0 | 50090-7372 | A-S Medication Solutions | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (50090-7372-0) | October 18, 2024 |
| 50090-7372-1 | 50090-7372 | A-S Medication Solutions | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE (50090-7372-1) | October 18, 2024 |
| 50090-7372-2 | 50090-7372 | A-S Medication Solutions | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE (50090-7372-2) | October 18, 2024 |
| 50090-7372-3 | 50090-7372 | A-S Medication Solutions | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (50090-7372-3) | October 18, 2024 |
| 50090-7373-0 | 50090-7373 | A-S Medication Solutions | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (50090-7373-0) | October 18, 2024 |
| 71335-2354-1 | 71335-2354 | Bryant Ranch Prepack | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2354-1) | May 22, 2024 |
| 71335-2354-2 | 71335-2354 | Bryant Ranch Prepack | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2354-2) | May 24, 2024 |
| 71335-2354-3 | 71335-2354 | Bryant Ranch Prepack | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2354-3) | March 12, 2024 |
| 71335-2354-4 | 71335-2354 | Bryant Ranch Prepack | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2354-4) | February 7, 2024 |
| 71335-2354-5 | 71335-2354 | Bryant Ranch Prepack | 120 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2354-5) | April 11, 2024 |
| 71335-2354-6 | 71335-2354 | Bryant Ranch Prepack | 15 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2354-6) | April 2, 2024 |
| 71335-2354-7 | 71335-2354 | Bryant Ranch Prepack | 45 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2354-7) | August 26, 2024 |
| 71335-2354-8 | 71335-2354 | Bryant Ranch Prepack | 180 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2354-8) | August 26, 2024 |
| 71335-2354-9 | 71335-2354 | Bryant Ranch Prepack | 20 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2354-9) | August 26, 2024 |
| 71335-2524-1 | 71335-2524 | Bryant Ranch Prepack | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2524-1) | November 25, 2024 |
| 71335-2524-2 | 71335-2524 | Bryant Ranch Prepack | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2524-2) | November 25, 2024 |
| 71335-2524-3 | 71335-2524 | Bryant Ranch Prepack | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2524-3) | November 25, 2024 |
| 71335-2524-4 | 71335-2524 | Bryant Ranch Prepack | 180 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2524-4) | November 25, 2024 |
| 71335-2524-5 | 71335-2524 | Bryant Ranch Prepack | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-2524-5) | November 25, 2024 |
| 72162-2424-0 | 72162-2424 | Bryant Ranch Prepack | 1000 TABLET, EXTENDED RELEASE in 1 BOTTLE (72162-2424-0) | July 31, 2018 |
| 72162-2424-1 | 72162-2424 | Bryant Ranch Prepack | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE (72162-2424-1) | July 31, 2018 |
| 72162-2424-2 | 72162-2424 | Bryant Ranch Prepack | 50 TABLET, EXTENDED RELEASE in 1 BOTTLE (72162-2424-2) | July 31, 2018 |
| 72162-2424-4 | 72162-2424 | Bryant Ranch Prepack | 180 TABLET, EXTENDED RELEASE in 1 BOTTLE (72162-2424-4) | July 31, 2018 |
| 72162-2424-5 | 72162-2424 | Bryant Ranch Prepack | 500 TABLET, EXTENDED RELEASE in 1 BOTTLE (72162-2424-5) | July 31, 2018 |
| 72162-2424-7 | 72162-2424 | Bryant Ranch Prepack | 360 TABLET, EXTENDED RELEASE in 1 BOTTLE (72162-2424-7) | July 31, 2018 |
| 72162-2424-9 | 72162-2424 | Bryant Ranch Prepack | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (72162-2424-9) | July 31, 2018 |
| 67046-0437-3 | 67046-0437 | Coupler LLC | 30 TABLET, EXTENDED RELEASE in 1 BLISTER PACK (67046-0437-3) | June 16, 2026 |
| 67046-1557-3 | 67046-1557 | Coupler LLC | 30 TABLET, EXTENDED RELEASE in 1 BLISTER PACK (67046-1557-3) | April 29, 2025 |
| 67046-1584-3 | 67046-1584 | Coupler LLC | 30 TABLET, EXTENDED RELEASE in 1 BLISTER PACK (67046-1584-3) | September 15, 2025 |
| 70010-491-01 | 70010-491 | Granules Pharmaceuticals Inc. | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE (70010-491-01) | July 31, 2018 |
| 70010-491-05 | 70010-491 | Granules Pharmaceuticals Inc. | 500 TABLET, EXTENDED RELEASE in 1 BOTTLE (70010-491-05) | July 31, 2018 |
| 70010-491-09 | 70010-491 | Granules Pharmaceuticals Inc. | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (70010-491-09) | April 16, 2020 |
| 70010-491-10 | 70010-491 | Granules Pharmaceuticals Inc. | 1000 TABLET, EXTENDED RELEASE in 1 BOTTLE (70010-491-10) | July 31, 2018 |
| 70010-491-18 | 70010-491 | Granules Pharmaceuticals Inc. | 5000 TABLET, EXTENDED RELEASE in 1 POUCH (70010-491-18) | June 14, 2019 |
| 70010-491-19 | 70010-491 | Granules Pharmaceuticals Inc. | 25000 TABLET, EXTENDED RELEASE in 1 CARTON (70010-491-19) | June 14, 2019 |
| 70010-492-01 | 70010-492 | Granules Pharmaceuticals Inc. | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE (70010-492-01) | July 31, 2018 |
| 70010-492-05 | 70010-492 | Granules Pharmaceuticals Inc. | 500 TABLET, EXTENDED RELEASE in 1 BOTTLE (70010-492-05) | July 31, 2018 |
| 70010-492-20 | 70010-492 | Granules Pharmaceuticals Inc. | 3500 TABLET, EXTENDED RELEASE in 1 POUCH (70010-492-20) | June 14, 2019 |
| 70010-492-21 | 70010-492 | Granules Pharmaceuticals Inc. | 17500 TABLET, EXTENDED RELEASE in 1 CARTON (70010-492-21) | June 14, 2019 |
| 50742-633-10 | 50742-633 | Ingenus Pharmaceuticals, LLC | 1000 TABLET, EXTENDED RELEASE in 1 BOTTLE (50742-633-10) | December 10, 2018 |
| 50742-633-60 | 50742-633 | Ingenus Pharmaceuticals, LLC | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE (50742-633-60) | December 10, 2018 |
| 50742-633-90 | 50742-633 | Ingenus Pharmaceuticals, LLC | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (50742-633-90) | December 10, 2018 |
| 50742-634-10 | 50742-634 | Ingenus Pharmaceuticals, LLC | 1000 TABLET, EXTENDED RELEASE in 1 BOTTLE (50742-634-10) | December 10, 2018 |
| 50742-634-30 | 50742-634 | Ingenus Pharmaceuticals, LLC | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (50742-634-30) | December 10, 2018 |
| 50742-634-60 | 50742-634 | Ingenus Pharmaceuticals, LLC | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE (50742-634-60) | December 10, 2018 |
| 68645-595-59 | 68645-595 | Legacy Pharmaceutical Packaging, LLC | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE (68645-595-59) | March 10, 2022 |
| 82804-147-30 | 82804-147 | Proficient Rx LP | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (82804-147-30) | April 8, 2025 |
| 82804-147-60 | 82804-147 | Proficient Rx LP | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE (82804-147-60) | September 20, 2024 |
| 82804-147-78 | 82804-147 | Proficient Rx LP | 180 TABLET, EXTENDED RELEASE in 1 BOTTLE (82804-147-78) | October 1, 2024 |
| 82804-147-90 | 82804-147 | Proficient Rx LP | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (82804-147-90) | November 4, 2024 |
| 70518-4370-0 | 70518-4370 | REMEDYREPACK INC. | 30 TABLET, EXTENDED RELEASE in 1 BLISTER PACK (70518-4370-0) | June 24, 2025 |
| 70518-4370-1 | 70518-4370 | REMEDYREPACK INC. | 100 POUCH in 1 BOX (70518-4370-1) / 1 TABLET, EXTENDED RELEASE in 1 POUCH (70518-4370-2) | June 24, 2025 |
| 70518-4370-3 | 70518-4370 | REMEDYREPACK INC. | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (70518-4370-3) | July 21, 2025 |
| 70518-4370-4 | 70518-4370 | REMEDYREPACK INC. | 180 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (70518-4370-4) | August 22, 2025 |
| 70518-4651-0 | 70518-4651 | REMEDYREPACK INC. | 30 POUCH in 1 BOX (70518-4651-0) / 1 TABLET, EXTENDED RELEASE in 1 POUCH (70518-4651-1) | April 30, 2026 |
| 50090-6516 | 50090-6516 | A-S Medication Solutions | — | July 31, 2018 |
| 50090-7372 | 50090-7372 | A-S Medication Solutions | — | July 31, 2018 |
| 50090-7373 | 50090-7373 | A-S Medication Solutions | — | July 31, 2018 |
| 71335-2354 | 71335-2354 | Bryant Ranch Prepack | — | July 31, 2018 |
| 71335-2524 | 71335-2524 | Bryant Ranch Prepack | — | July 31, 2018 |
| 72162-2424 | 72162-2424 | Bryant Ranch Prepack | — | July 31, 2018 |
| 67046-0437 | 67046-0437 | Coupler LLC | — | June 16, 2026 |
| 67046-1557 | 67046-1557 | Coupler LLC | — | April 29, 2025 |
| 67046-1584 | 67046-1584 | Coupler LLC | — | September 15, 2025 |
| 70010-491 | 70010-491 | Granules Pharmaceuticals Inc. | — | July 31, 2018 |
| 70010-492 | 70010-492 | Granules Pharmaceuticals Inc. | — | July 31, 2018 |
| 50742-633 | 50742-633 | Ingenus Pharmaceuticals, LLC | — | December 10, 2018 |
| 50742-634 | 50742-634 | Ingenus Pharmaceuticals, LLC | — | December 10, 2018 |
| 68645-595 | 68645-595 | Legacy Pharmaceutical Packaging, LLC | — | March 10, 2022 |
| 82804-147 | 82804-147 | Proficient Rx LP | — | July 31, 2018 |
| 70518-4370 | 70518-4370 | REMEDYREPACK INC. | — | June 24, 2025 |
| 70518-4651 | 70518-4651 | REMEDYREPACK INC. | — | April 30, 2026 |
Sources for this page
| Dataset | Agency | Used for |
|---|---|---|
| NDC Directory | FDA | Identity, ingredients, strengths, forms, routes, labelers, packages |
| Drugs@FDA | FDA | Application, sponsor, submissions, review documents, marketing status |
| Orange Book | FDA | Therapeutic equivalence codes, reference drug flags, patents, exclusivity |
| Drug Labeling | FDA / NLM | Prescribing information reproduced above |
| FAERS | FDA | Adverse event report counts |
| Enforcement | FDA | Recall records |
Generated September 25, 2026 · 13 sections on this page.