Metformin Hydrochloride 1000 mg Tablet, Film Coated, Extended Release, 60-count
Other active recalls for Metformin Hydrochloride (different manufacturers) — 2 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Biguanide class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Metformin is used alone or with other medications, including insulin, to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Metformin is in a class of drugs called biguanides. Metformin helps to control the amount of glucose (sugar) in your blood. It decreases the amount of glucose you absorb from your food and the amount of glucose made by your liver. Metformin also increases your body's response to insulin, a natural substance that controls the amount of glucose in the blood. Metformin is not used...
Read the full MedlinePlus article ↗- Metformin works in three ways: it lowers the amount of sugar your liver dumps into your bloodstream, slows how much sugar your gut absorbs from food, and helps your body respond to...
- What exactly is metformin doing for my diabetes?
- Yes, this is very common — diarrhea, nausea, and stomach discomfort are the most frequently reported side effects, and they're often worst when you first start or when your dose go...
- My stomach has been a mess since I started metformin. Is that normal? Will it get better?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Metformin Hydrochloride — tap one for details:
Metformin Hydrochloride may be associated with lower levels of 4 nutrients — worth a chat with your pharmacist, not a cause for alarm.
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Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII 7Z8S9VYZ4B
Ethylcellulose is a plant-derived thickener and film-former made by chemically modifying cellulose. It's used as a binder to hold tablet ingredients together, a coating to control how quickly medicine is released, or a thickener in liquid formulations.
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UNII VM7F0B23ZI
Hypromellose 2208 is a plant-derived thickening agent that forms a protective coating on tablets and capsules. It slows down how quickly the medicine dissolves, controlling drug release into your body.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII C9H2L21V7U
A fat derived from coconut or palm oil containing shorter fatty acid chains. It serves as a solvent and carrier to help dissolve or suspend active ingredients, improving absorption and stability in liquid formulations.
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UNII 2UMI9U37CP
Oleic acid is a naturally occurring fatty acid derived from plant or animal oils. It functions as an emulsifier and solvent in medicines, helping blend water and oil-based ingredients together and dissolving other components.
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UNII B697894SGQ
Polyethylene glycol 400 is a clear, thick liquid made from petroleum-derived polymers. It acts as a solvent and humectant in medicines, helping dissolve active ingredients and retain moisture in the formulation.
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UNII FZ989GH94E
Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 4ELV7Z65AP
Stearic acid is a fatty acid derived from plant or animal sources. It acts as a binder and lubricant in tablets and capsules, helping them hold together and flow smoothly during manufacturing.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
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UNII XHX3C3X673
Triacetin is a clear, oily liquid made from glycerin and acetic acid. It works as a plasticizer and solvent in medicines, helping soften coatings and improve how liquids mix together in formulations.
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UNII TTV12P4NEE
Xanthan gum is a thickening and stabilizing ingredient made from fermented corn or other sugars. It's added to medicines to improve texture, prevent separation of liquids and solids, and help the product stay consistent.
14 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $1.53 | $91.72 / 60 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Metformin Hydrochloride 1000 mg 00378-6001-91 | Mylan | 60 tablets | $0.326 | AB2 | Availability likely | — |
| Metformin Hydrochloride 1000 mg 11788-0038-60 | AiPing | 60 tablets | $0.326 | AB2 | Availability likely | — |
| Metformin hydrochloride 1000 mg 27241-0189-60 | Ajanta | 60 tablets | $0.326 | AB2 | Availability likely | — |
| metformin hydrochloride 1000 mg 42806-0406-60 | EPIC | 60 tablets | $0.326 | AB2 | Availability likely | — |
| Metformin Hydrochloride 1000 mg 59651-0043-60 | Aurobindo | 60 tablets | $0.326 | AB2 | Availability likely | — |
| Metformin Hydrochloride 1000 mg 69367-0413-60 | Westminster | 60 tablets | $0.326 | AB2 | Availability likely | — |
| Metformin Hydrochloride 1000 mg 70010-0497-09 | Granules | 90 tablets | $0.334 | AB3 | Availability likely | — |
| Metformin hydrochloride 1000 mg 27241-0241-90 | Ajanta | 90 tablets | $0.334 | AB3 | Availability likely | — |
| Metformin hydrochloride 1000 mg 68682-0018-90 | Oceanside | 90 tablets | $2.193 | — | FDA listed | — |
| Metformin Hydrochloride 1000 mg 50228-0504-05 | ScieGen | 500 tablets | — | AB2 | FDA listed | — |
| Metformin 1000 mg 50742-0634-10 | Ingenus | 1000 tablets | — | AB2 | FDA listed | — |
| Metformin Hydrochloride 1000 mgthis 51407-0059-60 | Golden | 60 tablets | — | AB2 | FDA listed | — |
| Metformin Hydrochloride 1000 mg 63629-5934-01 | Bryant | 30 tablets | — | AB2 | FDA listed | — |
| Metformin 1000 mg 67046-1584-03 | Coupler | 30 tablets | — | AB2 | FDA listed | — |
| Metformin Hydrochloride 1000 mg 68180-0337-01 | Lupin | 100 tablets | — | AB2 | FDA listed | — |
| Metformin Hydrochloride 1000 mg 68788-8520-06 | Preferred | 60 tablets | — | AB2 | FDA listed | — |
| Metformin Hydrochloride 1000 mg 70247-0018-60 | Qingdao | 60 tablets | — | AB2 | FDA listed | — |
| Metformin Hydrochloride 1000 mg 70518-4369-00 | REMEDYREPACK | 1 tablet | — | AB2 | FDA listed | — |
| Metformin 1000 mg 70518-4651-00 | REMEDYREPACK | 1 tablet | — | AB2 | FDA listed | — |
| Metformin hydrochloride 1000 mg 70518-4652-00 | REMEDYREPACK | 1 tablet | — | AB2 | FDA listed | — |
| Metformin Hydrochloride 1000 mg 43547-0504-09 | Solco | 90 tablets | — | AB3 | FDA listed | — |
| Metformin Hydrochloride 1000 mg 47335-0306-18 | Sun | 1000 tablets | — | — | Discontinued | — |
| Metformin Hydrochloride 1000 mg 72664-0228-90 | VGYAAN | 90 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride 1000 mg 62207-0497-47 | Granules | 500 tablets | — | AB3 | FDA listed | — |
| Glumetza 1000 mg 68012-0003-16 | Santarus, | 90 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride 1000 mg 33342-0378-10 | Macleods | 90 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride 1000 mg 42571-0334-01 | Micro | 100 tablets | — | AB3 | FDA listed | — |
| Metformin Hydrochloride 1000 mg 68462-0521-01 | GLENMARK | 100 tablets | — | AB3 | FDA listed | — |
| Metformin Hydrochloride 1000 mg 68180-0339-01 | Lupin | 100 tablets | — | AB3 | FDA listed | — |
| Metformin Hydrochloride 1000 mg 70518-4677-00 | REMEDYREPACK | 90 tablets | — | AB3 | FDA listed | — |
| Metformin Hydrochloride 1000 mg 70518-4710-00 | REMEDYREPACK | 1 tablet | — | AB2 | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 51407-0059-60 You're viewing this | 60 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (51407-059-60) | 2018-03-12 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed 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 ( 2.2 ), 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 ) ]. 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 ▾
1 INDICATIONS AND USAGE Metformin hydrochloride extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Metformin hydrochloride extended-release tablet are 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 ▾
2 DOSAGE AND ADMINISTRATION Swallow Metformin hydrochloride extended-release tablets whole and never crush, cut or chew ( 2.1 ) Starting dose: 500 mg orally once daily with the evening meal ( 2.1 ) Increase the dose in increments of 500 mg weekly, up to a maximum of 2,000 mg once daily with the evening meal ( 2.1 ) Patients receiving metformin hydrochloride (HCl) tablets may be switched to metformin hydrochloride extended-release tablets once daily at the same total daily dose, up to 2,000 mg once daily ( 2.1 ) Renal Impairment: Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR) ( 2.2 ) Do not use in patients with eGFR below 30 mL/minute/1.73 m 2 ( 2.2 ) Initiation is not recommended in patients with eGFR between 30 to 45 mL/minute/1.73 m 2 ( 2.2 ) Assess risk/benefit of continuing if eGFR falls below 45 mL/minute/1.73 m 2 ( 2.2 ) Discontinue if eGFR falls below 30 mL/minute/1.73 m 2 ( 2.2 ) Discontinuation for Iodinated Contrast Imaging Procedures: Metformin hydrochloride extended-release tablets may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures ( 2.3 )
2.1Adult Dosage and Administration Swallow Metformin hydrochloride extended-release tablets whole and never crush, cut or chew. The recommended starting dose of Metformin hydrochloride extended-release tablets are 500 mg orally once daily with the evening meal. Increase the dose in increments of 500 mg weekly on the basis of glycemic control and tolerability, up to a maximum of 2,000 mg once daily with the evening meal.
If glycemic control is not achieved with Metformin hydrochloride extended-release tablets 2,000 mg once daily, consider a trial of Metformin hydrochloride extended-release tablets 1,000 mg twice daily. Patients receiving metformin hydrochloride (HCl) may be switched to Metformin hydrochloride extended-release tablets once daily at the same total daily dose, up to 2,000 mg once daily.
2.2Recommendations for Use in Renal Impairment Assess renal function prior to initiation of Metformin hydrochloride extended-release tablets and periodically thereafter. Metformin hydrochloride extended-release tablets are contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m 2 . Initiation of Metformin hydrochloride extended-release tablets in patients with an eGFR between 30 to 45 mL/minute/1.73 m 2 is not recommended.
In patients taking Metformin hydrochloride extended-release tablets whose eGFR later falls below 45 mL/min/1.73 m 2 , assess the benefit risk of continuing therapy. Discontinue Metformin hydrochloride extended-release tablets if the patient's eGFR later falls below 30 mL/minute/1.73 m 2 [ see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 ) ].
2.3Discontinuation for Iodinated Contrast Imaging Procedures Discontinue Metformin hydrochloride extended-release tablets at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m 2 ; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart Metformin hydrochloride extended-release tablets if renal function is stable.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Metformin hydrochloride extended-release tablets, USP are available as: 500 mg extended-release, white to off-white, film coated, modified capsule-shaped tablets debossed with “ NF5 ” on one side. 1,000 mg extended-release, white to off-white, film coated, modified capsule-shaped tablets debossed with “ NF0 ” on one side. Extended-Release Tablets: 500 mg and 1,000 mg ( 3 )
⛔ Contraindications ▾
4 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 ▾
5 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 )
5.1Lactic 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 ) ]: Before initiating Metformin hydrochloride extended-release tablets, obtain an estimated glomerular filtration rate (eGFR). Metformin hydrochloride extended-release tablets are contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 [see Contraindications ( 4 ) ].
Initiation of Metformin hydrochloride extended-release tablets are not recommended in patients with eGFR between 30 to 45 mL/min/1.73 m 2 . 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.
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 )] . Co…
🤒 Adverse Reactions ▾
6 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 ) ] 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 Nostrum Laboratories, Inc. at [email protected] or call at 1-877-770-1285 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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.
Table 1: Adverse Reactions from Clinical Trials of Metformin HCl Extended-Release Tablets Occurring >5% and More Common than Placebo in Patients with Type 2 Diabetes Mellitus Adverse Reaction Metformin HCl Extended-Release Tablets (n=781) Placebo (n=195) Diarrhea 10% 3% Nausea/Vomiting 7% 2% 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.
6.2Postmarketing 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.
🔄 Drug Interactions ▾
7 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 hxtended-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 ▾
8 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 )
8.1Pregnancy 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 to 10% in women with pre-gestational diabetes mellitus with an HbA 1C >7 and has been reported to be as high as 20 to 25% in women with a HbA 1C >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 HCl 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.
8.2Lactation 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.
8.3Females and Males of Reproductive Potential Discuss the potential for unintended pregnancy with premenopausal women as therapy with Metformin hydrochloride extended-…
🤰 Pregnancy ▾
8.1Pregnancy 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 to 10% in women with pre-gestational diabetes mellitus with an HbA 1C >7 and has been reported to be as high as 20 to 25% in women with a HbA 1C >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 HCl 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.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of Metformin hydrochloride extended-release tablets in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Controlled clinical studies of Metformin hydrochloride extended-release tablets did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis. Assess renal function more frequently in elderly patients [ see Warnings and Precautions ( 5.1 ) ].
🆘 Overdosage ▾
10 OVERDOSAGE Overdose of metformin HCl 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
12.3Pharmacokinetics Absorption In a multiple-dose crossover study, 23 patients with type 2 diabetes mellitus were administered either Metformin hydrochloride extended-release tablets 2,000 mg once a day (after dinner) or metformin HCl tablets 1,000 mg twice a day (after breakfast and after dinner). After 4 weeks of treatment, steady-state pharmacokinetic parameters, area under the concentration-time curve (AUC), time to peak plasma concentration (T max ), and maximum concentration (C max ) were evaluated. The appearance of metformin in plasma from Metformin hydrochloride extended-release tablets are slower and more prolonged compared to metformin HCl tablets.
Results are presented in Table 3. Table 3: Metformin hydrochloride extended-release tablets vs. Metformin HCl Tablets Steady- State Pharmacokinetic Parameters at 4 Weeks Pharmacokinetic Parameters (mean ± SD) Metformin hydrochloride extended-release tablets 2,000 mg (administered q.d. after dinner) Metformin HCl tablets Immediate-release metformin HCl tablets 2,000 mg (1,000 mg b.i.d.) AUC 0-24hr (ng•hr/mL) 26,811 ± 7055 27,371 ± 5,781 T max (hr) 6 (3 to 10) 3 (1 to 8) C max (ng/mL) 2849 ± 797 1820 ± 370 In four single-dose studies and one multiple-dose study, the bioavailability of Metformin hydrochloride extended-release tablets 2,000 mg given once daily, in the evening, under fed conditions [as measured by AUC] was similar to the same total daily dose administered as metformin HCl tablets 1,000 mg given twice daily.
The geometric mean ratios (Metformin hydrochloride extended-release tablets / metformin HCL tablets) of AUC 0-24hr , AUC 0-72hr , and AUC 0-inf for these five studies ranged from 0.96 to 1.08. In a single-dose, four-period replicate crossover design study, comparing two 500 mg Metformin hydrochloride extended-release tablets to one 1,000 mg Metformin hydrochloride extended-release tablet administered in the evening with food to 29 healthy male subjects, two 500 mg Metformin hydrochloride extended-release tablets were found to be equivalent to one 1,000 mg Metformin hydrochloride extended-release tablet.
In a study carried out with Metformin hydrochloride extended-release tablets, there was a dose-associated increase in metformin exposure over 24 hours following oral administration of 1,000, 1,500, 2,000, and 2,500 mg. In three studies with Metformin hydrochloride extended-release tablets using different treatment regimens (2,000 mg after dinner; 1,000 mg after breakfast and after dinner; and 2,500 mg after dinner), the pharmacokinetics of metformin as measured by AUC appeared linear following multiple-dose administration.
Effect of food : The extent of metformin absorption (as measured by AUC) from Metformin hydrochloride extended-release tablets increased by approximately 60% when given with food. When Metformin hydrochloride extended-release tablets was administered with food, C max was increased by approximately 30% and T max was more prolonged compared with the fasting state (6.1 versus 4.0 hours). Distribution The apparent volume of distribution (V/F) of metformin following single oral doses of metformin HCl tablets 850 mg averaged 654 ± 358 L.
Metformin is negligibly bound to plasma proteins. Metformin partitions into erythrocytes, most likely as a function of time. Metabolism Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic me…
🧬 Mechanism of Action ▾
12.1Mechanism 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Metformin hydrochloride extended-release tablets, USP as are supplied as modified capsule-shaped, film-coated extended-release tablets containing 500 mg or 1,000 mg of metformin hydrochloride. NDC 51407-058-60: 500 mg extended-release, white to off-white, film coated, modified capsule-shaped tablets debossed with “NF5” on one side: bottles of 60. NDC 51407-059-60: 1,000 mg extended-release, white to off-white, film coated, modified capsule-shaped tablets debossed with “NF0” on one side: bottles of 60.
16.2Storage Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature] excursions permitted to 15° to 30°C (59° to 86°F). Avoid excessive heat and humidity. Keep tightly closed (protect from moisture). Protect from light. Dispense in a tight, light-resistant container as defined in the USP.
16.1How Supplied Metformin hydrochloride extended-release tablets, USP as are supplied as modified capsule-shaped, film-coated extended-release tablets containing 500 mg or 1,000 mg of metformin hydrochloride. NDC 51407-058-60: 500 mg extended-release, white to off-white, film coated, modified capsule-shaped tablets debossed with “NF5” on one side: bottles of 60. NDC 51407-059-60: 1,000 mg extended-release, white to off-white, film coated, modified capsule-shaped tablets debossed with “NF0” on one side: bottles of 60.
📋 Description ▾
11 DESCRIPTION Metformin hydrochloride extended-release tablets, USP contain the biguanidine antihyperglycemic agent, metformin, in the form of monohydrochloride salt. The chemical name of metformin HCl is N, N-dimethylimidodicarbonimidic diamide hydrochloride with a molecular formula of C 4 H 11 N 5 •HCl and a molecular weight of 165.63. Its structural formula is: Metformin HCl is a white to off-white crystalline powder that is freely soluble in water and is practically insoluble in acetone, ether, and chloroform.
The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin HCl is 6.68. Metformin hydrochloride extended-release tablets, USP deliver 500 mg or 1,000 mg of metformin HCl, which is equivalent to 389.93 mg or 779.86 mg metformin, respectively.
In addition to the active ingredient metformin HCl, each tablet contains the following inactive ingredients: ammonium hydroxide, ethylcellulose, hypromellose, lactose monohydrate, medium chain triglycerides, oleic acid, polyethylene glycol, povidone, silicified microcrystalline cellulose, stearic acid, titanium dioxide, talc, triacetin and xanthan gum. USP dissolution test is pending Image
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Lactic Acidosis Explain the risks of lactic acidosis, its symptoms, and conditions that predispose to its development. Advise patients to discontinue Metformin hydrochloride extended-release tablets immediately and to promptly notify their healthcare provider if unexplained hyperventilation, myalgias, malaise, unusual somnolence or other nonspecific symptoms occur.
Counsel patients against excessive alcohol intake and inform patients about importance of regular testing of renal function while receiving Metformin hydrochloride extended-release tablets. Instruct patients to inform their doctor that they are taking Metformin hydrochloride extended-release tablets prior to any surgical or radiological procedure, as temporary discontinuation may be required [ see Warnings and Precautions ( 5.1 ) ]. Hypoglycemia Inform patients that hypoglycemia may occur when Metformin hydrochloride extended-release tablets are coadministered with oral sulfonylureas and insulin.
Explain to patients receiving concomitant therapy the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development [ see Warnings and Precautions ( 5.3 ) ]. Vitamin B 12 Deficiency Inform patients about importance of regular hematological parameters while receiving Metformin hydrochloride extended-release tablets [ see Warnings and Precautions ( 5.2 ) ]. Females of Reproductive Age Inform females that treatment with Metformin hydrochloride extended-release tablets may result in ovulation in some premenopausal anovulatory women which may lead to unintended pregnancy [ see Use in Specific Populations ( 8.3 ) ].
Administration Information Inform patients that Metformin hydrochloride extended-release tablets must be swallowed whole and not crushed, cut, or chewed, and that the inactive ingredients may occasionally be eliminated in the feces as a soft mass that may resemble the original tablet. Manufactured by: Nostrum Laboratories, Inc Kansas City, MO 64120 Rev. January 2019 Marketed by: GSMS, Inc.
Camarillo, CA 93012 USA