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METFORMIN HYDROCHLORIDE EXTENDED RELEASE
Metformin Hydrochloride · 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 |
|---|---|---|---|---|---|---|---|
| 090295-001 | METFORMIN HYDROCHLORIDE | TABLET, EXTENDED RELEASE | METFORMIN HYDROCHLORIDE | Prescription | AB1 | ||
| 090295-002 | 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 | 10 | Labeling | Approved | August 11, 2026 | Standard |
| Supplement | 3 | Labeling | Approved | June 25, 2021 | Standard |
| Supplement | 2 | Labeling | Approved | June 25, 2021 | Standard |
| Original application | 1 | Approved | April 29, 2016 | — |
Prescribing information
Source: openFDA Drug LabelingReproduced verbatim from the Structured Product Labeling submitted to the FDA (effective 20260707). This is the manufacturer's labelling text, not a summary and not advice.
Boxed Warning
openFDA Drug LabelingBOXED WARNING WARNING: 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 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, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided [see Dosage and Administration (2.3), Contraindications (4), Warnings and Precautio ns (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 haemodialysis is recommended [see Warnings and Precautions (5.1) ]. 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, and hepatic impairment. 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)
Indications and Usage
openFDA Drug Labeling1 INDICATIONS & USAGE Metformin Hydrochloride Extended-Release Tablets, USP is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Metformin Hydrochloride Extended-Release Tablet is a biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. (1)
Dosage and Administration
openFDA Drug LabelingThere is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with metformin hydrochloride extended-release tablets or any other pharmacologic agent. Dosage of metformin hydrochloride extended-release tablets must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses. The maximum recommended daily dose of metformin hydrochloride extended-release tablets in adults is 2000 mg. Metformin hydrochloride extended-release tablets should generally be given once daily with the evening meal. Metformin hydrochloride extended-release tablets should be started at a low dose, with gradual dose escalation, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient. During treatment initiation and dose titration (see Recommended Dosing Schedule), fasting plasma glucose should be used to determine the therapeutic response to metformin hydrochloride extended-release tablets and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of metformin hydrochloride extended-release tablets, either when used as monotherapy or in combination with sulfonylurea or insulin. Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication, and secondary failure, i.e., loss of an adequate blood glucose lowering response after an initial period of effectiveness. Short-term administration of metformin hydrochloride extended-release tablets may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone. Metformin hydrochloride extended-release tablets must be swallowed whole and never crushed or chewed. Occasionally, the inactive ingredients of metformin hydrochloride extended-release tablets 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 tablet 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 2000 mg once daily, a trial of metformin hydrochloride extended-release tablets 1000 mg twice daily should be considered. 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 Pediatrics – Safety and effectiveness of metformin hydrochloride extended-release tablets in pediatric patients have not been established. Transfer From Other Antidiabetic Therapy When transferring patients from standard oral hypoglycemic agents other than chlorpropamide to metformin hydrochloride extended-release tablets, no transition period generally is necessary. When transferring …
Dosage Forms and Strengths
openFDA Drug Labeling3 DOSAGE FORMS & STRENGTHS Metformin Hydrochloride Extended-Release Tablet is available as: 500 mg: white to off-white, capsule shaped, biconvex tablets, debossed with ‘101’ on one side and plain on other side. 750 mg: white to off-white, capsule shaped, biconvex tablets, debossed with ‘102’ on one side and plain on other side. Metformin Hydrochloride Extended-Release Tablets, USP: 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 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 hydrochloride 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 (2.1), 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, is 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 30-45 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. Consider more frequent monitoring of patients. Age 65 or greater —The risk of metformin-associated lactic acidosis increases with the patient’s age because elderly patients have a greater likelihood of having hepatic, renal, or cardiac impairment than younger patients. Assess renal function more frequently in elderly patients. Radiologic studies with contrast — Administration of intravascular iodinated contrast agents in metformin-treated patients has led to an acute decrease in renal function and t …
Warnings
openFDA Drug LabelingLactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin hydrochloride extended-release tablets; 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 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 hydrochloride extended-release tablets and by use of the minimum effective dose of metformin hydrochloride extended-release tablets. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin hydrochloride extended-release tablets 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 hydrochloride extended-release tablets 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 hydrochloride extended-release tablets 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 extended-release tablets, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, metformin hydrochloride extended-release tablets 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 extended-release tablets 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 hydrochlori …
Adverse Reactions
openFDA Drug Labeling6 ADVERSE REACTIONS 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. Metformin Hydrochloride Extended-Release Tablets In placebo-controlled trials, 781 patients were administered metformin hydrochloride extended-release tablets. Adverse reactions reported in greater than 5% of the metformin hydrochloride extended-release tablets patients, and that were more common in metformin hydrochloride extended-release tablet -than placebo-treated patients, are listed in Table 2. Table 2: Adverse Reactions from Clinical Trials of Metformin Hydrochloride Extended-Release Tablets Occurring >5% and More Common than Placebo in Patients with Type 2 Diabetes Mellitus Metformin Hydrochloride Extended-Release Tablets (n=781) Placebo (n=195) Diarrhea 10% 3% Nausea/Vomiting 7% 2% Diarrhea led to discontinuation of metformin hydrochloride extended-release tablets in 0.6% of patients. Additionally, the following adverse reactions were reported in ≥1.0% to ≤5.0% of metformin hydrochloride extended-release tablets 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. 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. For metformin hydrochloride extended-release tablets, the most common adverse reactions (>5.0%) are diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Time-Cap Labs at 1-877-376-4271 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
Drug Interactions
openFDA Drug Labeling7 DRUG INTERACTIONS Table 3 presents clinically significant drug interactions with metformin hydrochloride extended-release tablets. Table 3: 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 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 2550 mg clinical dose, based on body surface area [see Data]. The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes mellitus with an HbA1C >7 and has been reported to be as high as 20–25% 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 2–4% and 15–20%, 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 2550 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 todefinitely 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 & MALES OF REPRODUCTIVE POTENTIAL Discuss the potential for unintended pregnancy with premenopausal women as therapy with metformin hydrochloride extended-release tablets may r …
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 Labeling11 DESCRIPTION Metformin Hydrochloride Extended-Release Tablets, USP contain the antihyperglycemic agent metformin, which is a biguanide, in the form of monohydrochloride.The chemical name of Metformin hydrochloride is N, N -dimethylimidodicarbonimidic diamide hydrochloride. The structural formula is as shown below: Metformin hydrochloride is a white to off-white crystalline compound with a molecular formula of C 4 H 11 N 5 • HCl and a molecular weight of 165.63. It is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pK a of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. Metformin Hydrochloride Extended-Release Tablets, USP contain 500 mg or 750 mg of metformin hydrochloride, which is equivalent to 389.93 mg, 584.90 mg metformin base, respectively. Metformin Hydrochloride Extended-Release Tablets, 500 mg or 750 mg contains the inactive ingredients colloidal silicon dioxide, hypromellose and magnesium stearate. metformin structure
Overdosage
openFDA Drug Labeling10 OVERDOSAGE 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 Metformin Hydrochloride Extended-Release Tablets, USP 500 mg Bottles of 90 NDC 49483-623-09 500 mg Bottles of 100 NDC 49483-623-01 500 mg Bottles of 500 NDC 49483-623-50 500 mg Bottles of 1000 NDC 49483-623-10 750 mg Bottles of 100 NDC 49483-624-01 750 mg Bottles of 500 NDC 49483-624-50 Metformin Hydrochloride Extended-Release Tablets, USP 500 mg arewhite to off-white, capsule shaped, biconvex tablets, debossed with '101' on one side and plain on other side. Metformin Hydrochloride Extended-Release Tablets, USP 750 mg are white to off-white, capsule shaped, biconvex tablets, debossed with '102' on one side and plain on other side Storage Store at 20°–25° C (68°–77° F); excursions permitted to 15°–30° C (59°–86° F). [See USP Controlled Room Temperature.] Dispense in a light-resistant container. Rx Only Manufactured for: Time-Cap Labs, Inc. 7 Michael Avenue, Farmingdale NY 11735, USA Manufactured by: Marksans Pharma Ltd. Plot No.L-82, L-83, Vema Indl. Estate, Vema, Goa-403 722, India Rev. 06/23
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 | November 11, 2020 | Direct Rx | CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level (per manufacturer) | Terminated |
| Class II | November 11, 2020 | PD-Rx Pharmaceuticals, Inc. | CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level (per manufacturer) | Terminated |
| Class II | November 11, 2020 | Marksans Pharma Limited | CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level | Terminated |
| Class II | November 11, 2020 | Marksans Pharma Limited | CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level | Terminated |
| Class II | November 11, 2020 | PD-Rx Pharmaceuticals, Inc. | CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level (per manufacturer) | Terminated |
| Class II | July 1, 2020 | Marksans Pharma Limited | CGMP Deviations: FDA analysis detected N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level | Terminated |
| Class II | July 1, 2020 | PD-Rx Pharmaceuticals, Inc. | CGMP Deviations: FDA analysis detected N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level | Terminated |
Packaging and NDCs
Source: NDC Directory| Package NDC | Product NDC | Labeler | Description | Marketing start |
|---|---|---|---|---|
| 71610-454-30 | 71610-454 | Aphena Pharma Solutions - Tennessee, LLC | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (71610-454-30) | August 10, 2020 |
| 71610-454-53 | 71610-454 | Aphena Pharma Solutions - Tennessee, LLC | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (71610-454-53) | August 10, 2020 |
| 71610-454-60 | 71610-454 | Aphena Pharma Solutions - Tennessee, LLC | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (71610-454-60) | August 7, 2020 |
| 71610-454-70 | 71610-454 | Aphena Pharma Solutions - Tennessee, LLC | 120 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (71610-454-70) | August 10, 2020 |
| 71610-454-80 | 71610-454 | Aphena Pharma Solutions - Tennessee, LLC | 180 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (71610-454-80) | August 7, 2020 |
| 71610-454-92 | 71610-454 | Aphena Pharma Solutions - Tennessee, LLC | 270 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (71610-454-92) | August 7, 2020 |
| 71610-454-94 | 71610-454 | Aphena Pharma Solutions - Tennessee, LLC | 360 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (71610-454-94) | November 2, 2021 |
| 71335-0293-1 | 71335-0293 | Bryant Ranch Prepack | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0293-1) | March 19, 2018 |
| 71335-0293-2 | 71335-0293 | Bryant Ranch Prepack | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0293-2) | October 30, 2018 |
| 71335-0293-3 | 71335-0293 | Bryant Ranch Prepack | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0293-3) | August 19, 2019 |
| 71335-0293-4 | 71335-0293 | Bryant Ranch Prepack | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0293-4) | March 2, 2018 |
| 71335-0293-5 | 71335-0293 | Bryant Ranch Prepack | 120 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0293-5) | March 23, 2018 |
| 71335-0293-6 | 71335-0293 | Bryant Ranch Prepack | 15 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0293-6) | February 14, 2018 |
| 71335-0293-7 | 71335-0293 | Bryant Ranch Prepack | 45 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0293-7) | February 23, 2022 |
| 71335-0293-8 | 71335-0293 | Bryant Ranch Prepack | 180 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0293-8) | February 16, 2018 |
| 71335-0293-9 | 71335-0293 | Bryant Ranch Prepack | 20 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0293-9) | February 23, 2022 |
| 71335-0889-1 | 71335-0889 | Bryant Ranch Prepack | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0889-1) | March 16, 2022 |
| 71335-0889-2 | 71335-0889 | Bryant Ranch Prepack | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0889-2) | March 16, 2022 |
| 71335-0889-3 | 71335-0889 | Bryant Ranch Prepack | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0889-3) | March 16, 2022 |
| 71335-0889-4 | 71335-0889 | Bryant Ranch Prepack | 180 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0889-4) | March 16, 2022 |
| 71335-0889-5 | 71335-0889 | Bryant Ranch Prepack | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE (71335-0889-5) | March 16, 2022 |
| 51655-555-96 | 51655-555 | Northwind Health Company, LLC | 180 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (51655-555-96) | December 30, 2025 |
| 68071-3111-2 | 68071-3111 | NuCare Pharmaceuticals, Inc. | 120 TABLET, EXTENDED RELEASE in 1 BOTTLE (68071-3111-2) | March 9, 2017 |
| 68071-3111-3 | 68071-3111 | NuCare Pharmaceuticals, Inc. | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (68071-3111-3) | March 9, 2017 |
| 68071-3111-6 | 68071-3111 | NuCare Pharmaceuticals, Inc. | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE (68071-3111-6) | March 9, 2017 |
| 68071-3111-8 | 68071-3111 | NuCare Pharmaceuticals, Inc. | 180 TABLET, EXTENDED RELEASE in 1 BOTTLE (68071-3111-8) | March 9, 2017 |
| 68071-3111-9 | 68071-3111 | NuCare Pharmaceuticals, Inc. | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (68071-3111-9) | March 9, 2017 |
| 43063-902-30 | 43063-902 | PD-Rx Pharmaceuticals, Inc. | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (43063-902-30) | March 26, 2019 |
| 43063-902-60 | 43063-902 | PD-Rx Pharmaceuticals, Inc. | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (43063-902-60) | November 1, 2018 |
| 72789-009-30 | 72789-009 | PD-Rx Pharmaceuticals, Inc. | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (72789-009-30) | September 18, 2019 |
| 72789-009-60 | 72789-009 | PD-Rx Pharmaceuticals, Inc. | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (72789-009-60) | September 20, 2019 |
| 72789-009-90 | 72789-009 | PD-Rx Pharmaceuticals, Inc. | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (72789-009-90) | September 13, 2019 |
| 72789-009-93 | 72789-009 | PD-Rx Pharmaceuticals, Inc. | 180 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (72789-009-93) | September 13, 2019 |
| 82804-148-00 | 82804-148 | Proficient Rx LP | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (82804-148-00) | September 20, 2024 |
| 82804-148-30 | 82804-148 | Proficient Rx LP | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (82804-148-30) | February 20, 2025 |
| 49483-623-01 | 49483-623 | TIME CAP LABORATORIES, INC | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (49483-623-01) | June 28, 2016 |
| 49483-623-09 | 49483-623 | TIME CAP LABORATORIES, INC | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (49483-623-09) | June 5, 2017 |
| 49483-623-10 | 49483-623 | TIME CAP LABORATORIES, INC | 1000 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (49483-623-10) | June 5, 2017 |
| 49483-623-50 | 49483-623 | TIME CAP LABORATORIES, INC | 500 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (49483-623-50) | June 28, 2016 |
| 49483-624-01 | 49483-624 | TIME CAP LABORATORIES, INC | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (49483-624-01) | May 12, 2016 |
| 49483-624-50 | 49483-624 | TIME CAP LABORATORIES, INC | 500 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (49483-624-50) | May 12, 2016 |
| 72189-064-30 | 72189-064 | direct rx | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (72189-064-30) | June 17, 2020 |
| 72189-064-90 | 72189-064 | direct rx | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (72189-064-90) | June 17, 2020 |
| 71610-454 | 71610-454 | Aphena Pharma Solutions - Tennessee, LLC | — | May 12, 2016 |
| 71335-0293 | 71335-0293 | Bryant Ranch Prepack | — | May 12, 2016 |
| 71335-0889 | 71335-0889 | Bryant Ranch Prepack | — | May 12, 2016 |
| 51655-555 | 51655-555 | Northwind Health Company, LLC | — | December 30, 2025 |
| 68071-3111 | 68071-3111 | NuCare Pharmaceuticals, Inc. | — | May 12, 2016 |
| 43063-902 | 43063-902 | PD-Rx Pharmaceuticals, Inc. | — | May 12, 2016 |
| 72789-009 | 72789-009 | PD-Rx Pharmaceuticals, Inc. | — | May 12, 2016 |
| 82804-148 | 82804-148 | Proficient Rx LP | — | May 12, 2016 |
| 49483-623 | 49483-623 | TIME CAP LABORATORIES, INC | — | May 12, 2016 |
| 49483-624 | 49483-624 | TIME CAP LABORATORIES, INC | — | May 12, 2016 |
| 72189-064 | 72189-064 | direct rx | — | June 17, 2020 |
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 · 12 sections on this page.