Metformin Hydrochloride 750 mg Tablet, Extended Release, 100-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 K679OBS311
Carboxymethylcellulose sodium is a plant-derived thickening agent made from cellulose. In medicines, it acts as a binder to hold ingredients together, a disintegrant to help the tablet break apart, or a thickener in liquids.
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UNII D9C330MD8B
Copovidone is a synthetic polymer made by combining two types of plastic-like molecules. It acts as a binder and film-former to help hold tablet ingredients together and improve how the medicine dissolves in your body.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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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.
5 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 ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.054 | $5.42 / 100 tablets |
| Medicaid paysCMS SDUD · 12 mo | $0.1269 | $12.69 / 100 tablets |
| Medicare drug plans payPart D · Q2 2026 | $0.1129 | $11.29 / 100 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Metformin Hydrochloride 750 mg 29300-0399-01 | Unichem | 100 tablets | $0.054 | AB1 | Availability likely | — |
| Metformin Hydrochloride 750 mg 42385-0978-01 | Laurus | 100 tablets | $0.054 | AB1 | Availability likely | — |
| Metformin Hydrochloride 750 mg 42806-0633-01 | Epic | 100 tablets | $0.054 | AB1 | Availability likely | — |
| Metformin Hydrochloride Extended Release 750 mg 49483-0624-01 | TIME | 100 tablets | $0.054 | AB1 | Availability likely | — |
| Metformin Hydrochloride 750 mg 50268-0551-15 | AvPAK | 1 tablet | $0.054 | AB1 | Availability likely | — |
| Metformin Hydrochloride 750 mg 62756-0143-01 | Sun | 100 tablets | $0.054 | — | Discontinued | — |
| Metformin Hydrochloride 750 mg 67877-0414-01 | Ascend | 100 tablets | $0.054 | AB | Availability likely | — |
| Metformin Hydrochloride 750 mgthis 68094-0804-50 | Precision | 100 tablets | $0.054 | AB1 | Availability likely | — |
| Metformin 750 mg 70010-0492-01 | Granules | 100 tablets | $0.054 | AB1 | Availability likely | — |
| Metformin Hydrochloride 750 mg 72578-0036-01 | Viona | 100 tablets | $0.054 | AB | Availability likely | — |
| Metformin hydrochloride ER 750 mg 76385-0129-01 | UNICHEM | 100 tablets | $0.054 | AB1 | Availability likely | — |
| Metformin ER 750 mg 82009-0118-01 | Quallent | 100 tablets | $0.054 | AB1 | Availability likely | — |
| Metformin Hydrochloride 750 mg 82009-0181-01 | Quallent | 100 tablets | $0.054 | AB | Availability likely | — |
| Metformin hydrochloride 750 mg 33342-0240-11 | Macleods | 100 tablets | $0.067 | AB1 | FDA listed | +23% |
| Metformin Hydrochloride 750 mg 51224-0107-50 | TAGI | 100 tablets | $0.067 | AB1 | FDA listed | +23% |
| Metformin Hydrochloride 750 mg 10135-0824-05 | Marlex | 500 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 25000-0102-03 | MARKSANS | 30 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride ER 750 mg 42291-0824-10 | AvKARE | 1000 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride Extended Release 750 mg 43063-0902-30 | PD-Rx | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 50090-5246-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| Metformin Hydrochloride 750 mg 50090-6839-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| Metformin 750 mg 50090-7372-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin 750 mg 50090-7373-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 50090-7534-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 50090-7535-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 51655-0077-26 | Northwind | 90 tablets | — | AB | FDA listed | — |
| Metformin Hydrochloride 750 mg 51655-0368-52 | Northwind | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 59651-0549-01 | Aurobindo | 100 tablets | — | AB1 | FDA listed | — |
| Metformin ER 750 mg 62207-0492-40 | Granules | 3500 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 63629-9147-01 | Bryant | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 65162-0179-03 | Amneal | 30 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride 750 mg 65841-0039-01 | Zydus | 100 tablets | — | AB | Discontinued | — |
| Metformin Hydrochloride 750 mg 67046-1556-03 | Coupler | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 68788-7205-01 | Preferred | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 69238-2126-01 | Amneal | 100 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride 750 mg 70518-2709-00 | REMEDYREPACK | 30 tablets | — | AB1 | Discontinued | — |
| Metformin Hydrochloride 750 mg 70518-4163-00 | REMEDYREPACK | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 71205-0141-00 | Proficient | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 71335-0776-01 | Bryant | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride Extended Release 750 mg 71335-0889-01 | Bryant | 30 tablets | — | AB1 | Discontinued | — |
| Metformin Hydrochloride 750 mg 71335-2504-01 | Bryant | 30 tablets | — | AB1 | FDA listed | — |
| Metformin 750 mg 71335-2524-01 | Bryant | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 71335-9752-01 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Metformin hydrochloride ER 750 mg 71610-0666-60 | Aphena | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 71610-0740-53 | Aphena | 60 tablets | — | — | FDA listed | — |
| Metformin hydrochloride ER 750 mg 71610-0867-53 | Aphena | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 72162-1293-01 | Bryant | 100 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride ER 750 mg 72789-0106-01 | PD-Rx | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 72789-0451-30 | PD-Rx | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 750 mg 72789-0472-01 | PD-Rx | 100 tablets | — | AB | FDA listed | — |
| Metformin Hydrochloride 750 mg 72789-0548-93 | PD-Rx | 180 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride Extended Release 750 mg 82804-0148-00 | Proficient | 100 tablets | — | AB1 | FDA listed | — |
Where does this data come from?
⏳ 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?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 68094-0804-50 You're viewing this | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE (68094-804-50) | $0.0542 / ea | $5.42 | 2024-02-15 | Active |
| 68094-0804-60 | 500 TABLET, EXTENDED RELEASE in 1 BOTTLE (68094-804-60) | $0.0542 / ea | $27.09 | 2024-02-15 | Active |
You're viewing the smallest of 2 pack sizes for this product.
This pack has the lowest per-ea cost of the 2 priced pack sizes ($0.0542 NADAC).
This pack accounts for about 42% of this product's recent Medicaid fills; most go to the 500 tablets pack. See all packs ↓
Pack size FAQ
What quantity is in NDC 68094-0804-50?
What is the difference between NDC 68094-0804-50 and NDC 68094-0804-60?
What NDC number is used to bill for this package of Metformin Hydrochloride 750 mg Tablet, Extended Release?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 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 (2.4) , 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 metforminassociated 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 and pediatric patients 10 years of age and older with type 2 diabetes mellitus. Metformin hydrochloride extended-release tablets are a 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 ▾
2 DOSAGE AND ADMINISTRATION Recommended Dosage in Adults and Pediatric Patients Aged 10 Years and Older: Swallow metformin hydrochloride extended-release tablets whole and never crush, cut or chew ( 2.2 ) Starting dosage: 500 mg orally once daily with the evening meal ( 2.2 ) Increase the dosage in increments of 500 mg weekly, up to a maximum dosage of 2,000 mg once daily with the evening meal ( 2.2 ) Patients receiving metformin hydrochloride immediate-release tablets may be switched to metformin hydrochloride extended-release tablets once daily at the same total daily dosage, up to 2,000 mg once daily ( 2.3 ) Recommended Dosage in Patients with Renal Impairment: Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR) ( 2.4 ) Do not use in patients with eGFR below 30 mL/minute/1.73 m 2 ( 2.4 ) Initiation is not recommended in patients with eGFR between 30 mL/minute/1.73 m 2 and 45 mL/minute/1.73 m 2 ( 2.4 ) Assess risk/benefit of continuing if eGFR falls below 45 mL/minute/1.73 m 2 ( 2.4 ) Discontinue if eGFR falls below 30 mL/minute/1.73 m 2 ( 2.4 ) 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 ( 2.5 )
2.2Recommended Dosage for Metformin Hydrochloride Extended-Release Tablets in Adults and Pediatric Patients Aged 10 Years and Older with Type 2 Diabetes Mellitus Swallow metformin hydrochloride extended-release tablets whole and never crush, cut or chew. The recommended starting dosage of metformin hydrochloride extended-release tablets is 500 mg orally once daily with the evening meal. Increase the dosage in increments of 500 mg weekly on the basis of glycemic control and tolerability, up to a maximum dosage 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. If a dose of metformin hydrochloride extended-release tablets is missed, instruct patients not to take two doses the same day and to resume their usual dose of metformin hydrochloride extended-release tablets with the next schedule dose.
2.3Switching Between Metformin Hydrochloride Immediate-Release Tablets and Metformin Hydrochloride Extended-Release Tablets Patients may switch between metformin hydrochloride immediate-release tablets and metformin hydrochloride extended-release tablets at the same total daily dosage. Patients receiving metformin hydrochloride extended-release tablets who require dosages higher than 2,000 mg daily may switch to metformin hydrochloride immediate-release tablets and titrate to the maximum total daily dosage of 2,550 mg.
2.4Recommended Dosage in Patients with 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 mL/minute/1.73 m 2 and 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 Warnings and Precautions (5.1) ] .
2.5Discontinuation 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 mL/min/1.73 m 2 and 60 mL/min/1.73 m 2 ; in patients with a history of liver disease, alcoholism,…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Metformin hydrochloride extended-release tablets, USP are available as: Metformin hydrochloride extended-release tablets USP, 500 mg are oval white tablets, with "OE" debossed on one side and "584" debossed on the other side. Metformin hydrochloride extended-release tablets USP, 750 mg are white, capsule shaped tablets, with "OE" debossed on one side and "585" debossed on the other side. Metformin Hydrochloride Extended-Release Tablets: 500 mg and 750 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. Metforminassociated 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 (2.2) , 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 is not recommended in patients with eGFR between 30 mL/min/1.73 m 2 and 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. Consider m…
🤒 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) ] 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 Precision Dose, Inc. at 1-800-397-9228 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. Metformin Hydrochloride Extended-Release Tablets In placebo-controlled trials, in adults with type 2 diabetes mellitus, 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 tablets - than placebo-treated patients, are listed in Table 1.
Table 1: Adverse Reactions from Clinical Trials of Metformin Hydrochloride Extended-Release Tablets Occurring > 5% and More Common than Placebo in Adults 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.
6.2Postmarketing 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 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 ▾
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 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.
8.2Lactation 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 hydrochlorid…
🤰 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 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.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of metformin hydrochloride extended-release tablets in pediatric patients as an adjunct to diet and exercise to improve glycemic control in pediatric patients 10 years of age and older with type 2 diabetes mellitus have been established. Use of metformin hydrochloride extended-release tablets for this indication is supported by evidence from adequate and well-controlled trials of metformin hydrochloride immediate-release tablets in adults with additional data from a controlled clinical trial of metformin hydrochloride immediate-release tablets in pediatric patients 10 to 16 years old with type 2 diabetes mellitus.
The safety and effectiveness of metformin extended-release tablets for glycemic control in pediatric patients less than 10 years of age with type 2 diabetes mellitus 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 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.
🧬 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 Following a single oral dose of metformin hydrochloride extended-release tablets, C max is achieved with a median value of 7 hours and a range of 4 to 8 hours. Peak plasma levels are approximately 20% lower compared to the same dose of metformin hydrochloride tablets, however, the extent of absorption (as measured by AUC) is comparable to metformin hydrochloride tablets. At steady state, the AUC and C max are less than dose proportional for metformin hydrochloride extended-release tablets within the range of 500 to 2,000 mg administered once daily.
Peak plasma levels are approximately 0.6, 1.1, 1.4 and 1.8 mcg/mL for 500, 1,000, 1,500, and 2,000 mg once-daily doses, respectively. The extent of metformin absorption (as measured by AUC) from metformin hydrochloride extended-release tablets at a 2,000 mg once-daily dose is similar to the same total daily dose administered as metformin hydrochloride tablets 1,000 mg twice daily. After repeated administration of metformin hydrochloride extended-release tablets, metformin did not accumulate in plasma.
Effect of food: Food decreases the extent of absorption and slightly delays the absorption of metformin, as shown by approximately a 40% lower mean peak plasma concentration (C max ), a 25% lower area under the plasma concentration versus time curve (AUC), and a 35-minute prolongation of time to peak plasma concentration (T max ) following administration of a single 850 mg tablet of metformin hydrochloride with food, compared to the same tablet strength administered fasting. Although the extent of metformin absorption (as measured by AUC) from the metformin hydrochloride extended-release tablets increased by approximately 50% when given with food, there was no effect of food on C max and T max of metformin.
Both high and low fat meals had the same effect on the pharmacokinetics of metformin hydrochloride extended-release tablets. Distribution The apparent volume of distribution (V/F) of metformin following single oral doses of metformin hydrochloride 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 metabolism (no metabolites have been identified in humans) nor biliary excretion. Elimination Renal clearance (see Table 3 ) is approximately 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of metformin elimination.
Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution. Specific Populations Patients with Renal Impairment In patients with decreased renal function the plasma and blood half-life of metformin is prolonged and the renal clearance is decreased (see Table 2 ) [See Dosage and Administration (2.4) , Contraindications (4) , Warnings and Precautions (5.1) and Use in Specific Populations (8.6) ] .
Patients with Hepatic Impairment No pharmacokinetic studies of metformin have been conducted in patients with hepatic impairment [See Warni…
🧬 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, 500 mg are oval white tablets, with "OE" debossed on one side and "584" debossed on the other side. They are available as follows: Bottles of 100 NDC 68094-904-50 Bottles of 500 NDC 68094-904-60 Bottles of 1,000 NDC 68094-904-70 Metformin hydrochloride extended-release tablets USP, 750 mg are white, capsule shaped tablets, with "OE" debossed on one side and "585" debossed on the other side. They are available as follows: Bottles of 100 NDC 68094-804-50 Bottles of 500 NDC 68094-804-60
16.2Storage Store at 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Dispense in light-resistant containers.
📦 Storage and Handling ▾
16.2Storage Store at 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Dispense in light-resistant containers.
📋 Description ▾
11 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 USP, 500 mg and 750 mg contain the inactive ingredients carboxymethylcellulose sodium, copovidone, hypromellose, magnesium stearate and microcrystalline cellulose. The USP dissolution test is pending.
Chemical Structure
💬 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) ].
Metformin Hydrochloride Extended-Release Tablets 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.
💬 Medication Guide ▾
Print patient information at: https://www.precisiondose.com/retail PATIENT INFORMATION Metformin Hydrochloride Extended-Release Tablets, USP (met for′ min hye″ droe klor′ ide) Read the Patient Information that comes with metformin hydrochloride extended-release tablets before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or treatment.
What is the most important information I should know about metformin hydrochloride extended-release tablets? Serious side effects can happen in people taking metformin hydrochloride extended-release tablets, including: Lactic Acidosis. Metformin hydrochloride, the medicine in metformin hydrochloride extended-release tablets, can cause a rare, but serious, side effect called lactic acidosis (a build-up of lactic acid in the blood) that can cause death.
Lactic acidosis is a medical emergency and must be treated in a hospital. Stop taking metformin hydrochloride extended-release tablets and call your healthcare provider right away if you get any of the following symptoms of lactic acidosis: feel very weak and tired have unusual (not normal) muscle pain have trouble breathing have unusual sleepiness or sleep longer than usual have unexplained stomach or intestinal problems with nausea and vomiting, or diarrhea feel cold, especially in your arms and legs feel dizzy or lightheaded have a slow or irregular heartbeat You have a higher chance of getting lactic acidosis if you: have kidney problems.
People whose kidneys are not working properly should not take metformin hydrochloride extended-release tablets. have liver problems. have congestive heart failure that requires treatment with medicines. drink a lot of alcohol (very often or short-term "binge" drinking). get dehydrated (lose a large amount of body fluids). This can happen if you are sick with a fever, vomiting, or diarrhea. Dehydration can also happen when you sweat a lot with activity or exercise and do not drink enough fluids. have certain x-ray tests with injectable dyes or contrast agents. have surgery. have a heart attack, severe infection, or stroke. are 80 years of age or older and have not had your kidney function tested.
What are metformin hydrochloride extended-release tablets? Metformin hydrochloride extended-release tablets are prescription medicines that contain metformin hydrochloride. Metformin hydrochloride extended-release tablets are used with diet and exercise to help control high blood sugar (hyperglycemia) in adults and children 10 years of age and older with type 2 diabetes.
Metformin hydrochloride extended-release tablets are not for people with type 1 diabetes. Metformin hydrochloride extended-release tablets are not for people with diabetic ketoacidosis (increased ketones in your blood or urine). It is not known if metformin hydrochloride extended-release tablets are safe and effective in children under 10 years of age.
Metformin hydrochloride extended-release tablets works longer in your body. This medicine helps control your blood sugar in a number of ways. These include helping your body respond better to the insulin it makes naturally, decreasing the amount of sugar your liver makes, and decreasing the amount of sugar your intestines absorb.
Metformin hydrochloride extended-release tablets do not cause your body to make more insulin. Who should not take metformin hydrochloride extended-release tablets? Some conditions increase your chance of getting lactic acidosis, or cause other problems if you take either of these medicines.
Most of the conditions listed below can increase your chance of getting lactic acidosis. Do not take metformin hydrochloride extended-release tablets if you: have kidney problems are allergic to the metformin hydrochloride in metformin hydrochloride extended-release tablets or any of the ingredients in metformin hydrochloride extended-release tablets. S…