Metformin Hydrochloride 500 mg Tablet, Extended Release, 100-count — NDC 68180-338-01 (Billing 68180-0338-01)
This is a package of 100 tablets of Metformin Hydrochloride 500 mg Tablet, Extended Release from Lupin Pharmaceuticals, Inc., marketed since Feb 2016 and currently FDA-listed; retail pharmacies pay about $0.2710 per tablet (NADAC). It is the main listing for this product, which comes in 3 package sizes.
Other active recalls for Metformin Hydrochloride (different manufacturers) — 2 · tap to view
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 061267
- GCN: 97061
- HICL (First Databank): 004763
- AHFS class code: 68:20.04.00
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
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.
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
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 | $0.271 | $27.10 / 100 tablets |
| Medicaid paysCMS SDUD · 12 mo | $0.4701 | $47.01 / 100 tablets |
| Medicare drug plans payPart D · Q2 2026 | $4.53 | $452.92 / 100 tablets |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 68180-0338-01 You're viewing this Main listing | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE | $0.2710 / ea | $27.10 | 2016-02-01 | — | Active |
| 68180-0338-02 68180-338-02 | 500 TABLET, EXTENDED RELEASE in 1 BOTTLE | — | — | 2016-02-01 | — | Active |
| 68180-0338-03 68180-338-03 | 1000 TABLET, EXTENDED RELEASE in 1 BOTTLE | — | — | 2016-02-01 | — | Active |
You're viewing the smallest of 3 pack sizes for this product.
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in this package?
How does this package differ from NDC 68180-0338-02?
What NDC number is used to bill for this package of Metformin Hydrochloride 500 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.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Metformin Hydrochloride 500 mg 42806-0632-01 | Epic | 100 tablets | $0.028 | AB1 | Availability likely | save 90% |
| Metformin Hydrochloride 500 mg 67877-0159-01 | Ascend | 100 tablets | $0.028 | AB1 | Availability likely | save 90% |
| Metformin Hydrochloride Er 500 mg 69315-0410-01 | Leading | 100 tablets | $0.028 | AB1 | Availability likely | save 90% |
| Metformin Hydrochloride Extended Release 500 mg 49483-0623-01 | TIME | 100 tablets | $0.028 | AB1 | Availability likely | save 90% |
| Metformin Hydrochloride 500 mg 42385-0977-01 | Laurus | 100 tablets | $0.028 | AB1 | Availability likely | save 90% |
| Metformin Hydrochloride 500 mg 50268-0550-15 | AvPAK | 1 tablet | $0.028 | AB1 | Availability likely | save 90% |
| Metformin Hydrochloride 500 mg 67877-0413-01 | Ascend | 100 tablets | $0.028 | AB1 | Availability likely | save 90% |
| Metformin Hydrochloride 500 mg 68094-0904-50 | Precision | 100 tablets | $0.028 | AB1 | Availability likely | save 90% |
| Metformin Hydrochloride 500 mg 82009-0180-05 | Quallent | 500 tablets | $0.028 | AB1 | Availability likely | save 90% |
| Metformin Hydrochloride 500 mg 29300-0389-01 | Unichem | 100 tablets | $0.028 | AB1 | Availability likely | save 90% |
| Metformin Hydrochloride 500 mg 62756-0142-01 | Sun | 100 tablets | $0.029 | — | FDA listed | save 89% |
| Metformin hydrochloride 500 mg 33342-0239-11 | Macleods | 100 tablets | $0.031 | AB1 | FDA listed | save 88% |
| Metformin Hydrochloride 500 mg 51224-0007-50 | TAGI | 100 tablets | $0.031 | AB1 | FDA listed | save 88% |
| Metformin Hydrochloride 500 mg 69367-0412-60 | Westminster | 60 tablets | $0.164 | AB2 | Availability likely | save 39% |
| Metformin hydrochloride 500 mg 27241-0188-60 | Ajanta | 60 tablets | $0.164 | AB2 | Availability likely | save 39% |
| Metformin Hydrochloride 500 mg 59651-0042-60 | Aurobindo | 60 tablets | $0.164 | AB2 | Availability likely | save 39% |
| Metformin hydrochloride 500 mg 27241-0240-01 | Ajanta | 100 tablets | $0.271 | AB3 | Availability likely | — |
| Metformin Hydrochloride 500 mg 42571-0333-01 | Micro | 100 tablets | $0.271 | AB3 | Availability likely | — |
| Metformin Hydrochloride 500 mg 50228-0445-01 | ScieGen | 100 tablets | $0.271 | AB3 | Availability likely | — |
| Metformin Hydrochloride 500 mgthis 68180-0338-01 | Lupin | 100 tablets | $0.271 | AB3 | Availability likely | — |
| Metformin Hydrochloride 500 mg 68462-0520-01 | GLENMARK | 100 tablets | $0.271 | AB3 | Availability likely | — |
| Metformin Hydrochloride 500 mg 70010-0496-01 | Granules | 100 tablets | $0.271 | AB3 | Availability likely | — |
| Metformin hydrochloride 500 mg 68682-0021-50 | Oceanside | 100 tablets | $0.402 | — | FDA listed | +48% |
| Glumetza 500 mg 68012-0004-50 | Santarus, | 100 tablets | $49.542 | — | FDA listed | +18180% |
| Metformin Hydrochloride 500 mg 43547-0503-10 | Solco | 100 tablets | — | AB3 | FDA listed | — |
| Metformin Hydrochloride 500 mg 47335-0305-18 | Sun | 1000 tablets | — | — | Discontinued | — |
| Metformin Hydrochloride 500 mg 62207-0496-47 | Granules | 500 tablets | — | AB3 | FDA listed | — |
| Glumetza 500 mg 68012-0002-13 | Santarus, | 100 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride 500 mg 71205-0186-20 | Proficient | 20 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71205-0686-30 | Proficient | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71610-0447-30 | Aphena | 30 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride Extended Release 500 mg 71610-0454-30 | Aphena | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71610-0533-30 | Aphena | 30 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 71610-0554-30 | Aphena | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71610-0578-60 | Aphena | 90 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 71610-0587-30 | Aphena | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71610-0652-30 | Aphena | 30 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride Extended-Release 500mg 500 mg 17224-0311-28 | Calvin | 28 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-5396-00 | A-S | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-5397-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71335-9683-01 | Bryant | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 72664-0227-01 | VGYAAN | 100 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride 500 mg 00615-8289-39 | NCS | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 51655-0559-25 | Northwind | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 51655-0853-25 | Northwind | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 65841-0027-01 | Zydus | 100 tablets | — | AB1 | Discontinued | — |
| Metformin Hydrochloride 500 mg 82804-0195-60 | Proficient | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 10135-0823-05 | Marlex | 500 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-7918-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 65162-0178-03 | Amneal | 30 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride Extended Release 500 mg 68071-3111-02 | NuCare | 120 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71610-0837-30 | Aphena | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 72578-0035-01 | Viona | 100 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 72789-0105-01 | PD-Rx | 100 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 76385-0128-01 | UNICHEM | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 67296-1701-06 | RedPharm | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 68180-0336-01 | Lupin | 100 tablets | — | AB2 | FDA listed | — |
| Metformin Hydrochloride 500 mg 69238-2125-01 | Amneal | 100 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride 500 mg 72789-0455-30 | PD-Rx | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71335-0886-01 | Bryant | 60 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 71610-0858-30 | Aphena | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 72789-0400-01 | PD-Rx | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-7579-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 63187-0779-00 | Proficient | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 25000-0101-03 | MARKSANS | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-7576-00 | A-S | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 59651-0548-25 | Aurobindo | 25000 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 68788-8814-01 | Preferred | 100 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 42291-0825-10 | AvKARE | 1000 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-1494-00 | A-S | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-7116-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 68788-8866-01 | Preferred | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 68788-8903-01 | Preferred | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride Extended Release 500 mg 72189-0064-30 | direct | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 72789-0454-60 | PD-Rx | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-7577-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71335-2568-01 | Bryant | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 42708-0201-60 | QPharma | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride Extended Release 500 mg 51655-0555-96 | Northwind | 180 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 68071-1419-02 | NuCare | 20 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride Extended Release 500 mg 71335-0293-01 | Bryant | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71335-0720-01 | Bryant | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 72189-0150-30 | direct | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride Extended Release 500 mg 72789-0009-30 | PD-Rx | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71335-3166-01 | Bryant | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 67296-2305-09 | Redpharm | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 70518-4639-00 | REMEDYREPACK | 1 tablet | — | AB1 | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
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?
- FDA Orange Book · refreshed Sep 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
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.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: LACTIC ACIDOSIS WARNING: LACTIC ACIDOSIS See full prescribing information for complete boxed warning Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.
( 5.1 ) Risk factors include renal impairment, concomitant use of certain drugs, age ≥ 65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, 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 tablet and institute general supportive measures in a hospital setting.
Prompt hemodialysis is recommended. ( 5.1 ) Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain.
Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio, and metformin plasma levels generally >5 mcg/mL [ see WARNINGS AND PRECAUTIONS ( 5.1 ) ]. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, 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 [ see DOSAGE AND ADMINISTRATION ( 2.2 ) , CONTRAINDICATIONS ( 4 ), WARNINGS AND PRECAUTIONS ( 5.1 ), and DRUG INTERACTIONS ( 7 )]. If metformin-associated lactic acidosis is suspected, immediately discontinue metformin hydrochloride extended-release tablet and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see WARNINGS AND PRECAUTIONS ( 5.1 )] .
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Metformin hydrochloride extended-release tablet is a biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1 ) 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.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Starting dose: 500 mg orally once daily with the evening meal ( 2.1 ) Increase the dose in increments of 500 mg every 1 to 2 weeks, 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 ) Swallow metformin hydrochloride extended-release tablets whole and never crush, cut or chew.
( 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 . Initiation is not recommended in patients with eGFR between 30 to 45 mL/minute/1.73 m 2 .
Assess risk/benefit of continuing metformin hydrochloride if eGFR falls below 45 mL/minute/1.73 m 2 . Discontinue if eGFR falls below 30 mL/minute/1.73 m 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 The recommended starting dose of metformin hydrochloride extended-release tablets is 500 mg orally once daily with the evening meal. Increase the dose in increments of 500 mg every 1 to 2 weeks on the basis of glycemic control and tolerability, up to a maximum of 2,000 mg once daily with the evening meal. 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.
Swallow metformin hydrochloride extended-release tablets whole and never crush, cut or chew. 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.
2.2Recommendations 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/minute/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 [see WARNINGS AND PRECAUTIONS ( 5.1 )] .
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Metformin Hydrochloride Extended-Release Tablets: 500 mg and 1,000 mg ( 3 ) Metformin hydrochloride extended-release tablets, 500 mg are available as white to off-white, oval shaped, biconvex coated tablet, debossed with "L41" on one side and "LU" on the other side. Metformin hydrochloride extended-release tablets, 1,000 mg are available as white to off-white, oval shaped, biconvex coated tablet, debossed with "L42" on one side and "LU" on the other side.
⛔ Contraindications ▾
4 CONTRAINDICATIONS Severe renal impairment: (eGFR below 30mL/minute/1.73 m 2 ) ( 4 , 5.1 ) Known hypersensitivity to metformin ( 4 ) Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma ( 4 ) Metformin hydrochloride extended-release tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30mL/minute/1.73 m 2 ) [see WARNINGS AND PRECAUTIONS ( 5.1 )] . Known hypersensitivity to metformin. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Lactic Acidosis: See boxed warning. ( 5.1 ) Vitamin B12 Deficiency: Metformin may lower vitamin B12 levels. Monitor hematologic parameters annually and vitamin B12 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, hypothermia, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/Liter), 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/minute 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 ) and 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/minute/1.73 m 2 [see CONTRAINDICATIONS ( 4 )] .
Initiation of metformin hydrochloride extended-release tablets is not recommended in patients with eGFR between 30 to 45 mL/minute/1.73 m 2 . Obtain an eGFR at least annually in all patients taking metformin hydrochloride extended-release tablets. In patients at increased 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 later falls below 45 mL/minute/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 [… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Adverse reactions occurring >5% in metformin hydrochloride clinical trials: hypoglycemia, diarrhea, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . The following adverse reactions are discussed in more detail in other sections of the labeling: Lactic Acidosis [see BOXED WARNING and WARNINGS AND PRECAUTIONS ( 5.1 )] Vitamin B 12 Deficiency [see WARNINGS AND PRECAUTIONS ( 5.2 )] Hypoglycemia [see WARNINGS AND PRECAUTIONS ( 5.3 )]
6.1Clinical Trials 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 clinical trials conducted in the U.S., over 1,000 patients with type 2 diabetes mellitus have been treated with metformin hydrochloride extended-release tablets 1,500 to 2,000 mg/day in active-controlled and placebo-controlled studies with the 500 mg dosage form.
In the add-on to sulfonylurea study, patients receiving background glyburide therapy were randomized to receive add-on treatment of either one of three different regimens of metformin hydrochloride extended-release tablets or placebo. In total, 431 patients received metformin hydrochloride extended-release tablets and glyburide and 144 patients received placebo and glyburide. Adverse reactions reported in greater than 5% of patients treated with metformin hydrochloride extended-release tablets that were more common in the combined metformin hydrochloride extended-release tablets and glyburide group than in the placebo and glyburide group are shown in Table 1.
In 0.7% of patients treated with metformin hydrochloride extended-release tablets and glyburide, diarrhea was responsible for discontinuation of study medication compared to no patients in the placebo and glyburide group. Table 1: Adverse Reactions Reported by >5% * of Patients for the Combined Metformin HydrochlorideExtended-Release TabletsGroups Versus Placebo Group * Adverse reactions that were more common in the metformin hydrochloride extended-release tablets-treated than in the placebo-treated patients. Adverse Reaction Metformin Hydrochloride Extended-Release Tablets + Glyburide (n = 431) Placebo + Glyburide (n = 144) Hypoglycemia 14% 5% Diarrhea 13% 6% Nausea 7% 4% 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 hydrochloride extended-release tablets. 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 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 ) 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.
👥 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 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 3 and 1 times, respectively, a 2,000 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 pregestational diabetes mellitus with an HbA1c >7 and has been reported to be as high as 20 to 25% in women with an 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 HCl was not teratogenic or embyrolethal when administered to rats prior to pregnancy through the period of organogenesis at doses up to 900 mg/kg, or when administered to rabbits during the period of organogenesis at doses up to 90 mg/kg.
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 and any potential adverse effects on the breastfed child from metformin hydrochloride 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 may result in ovulation in some anovulatory women.
8.4Pediatric Use Safety and effectiveness of metformin hydrochloride in pediatric patients have not been established.
8.5Geriatric Use Clinical studies of metformin hyd… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Limited data with metformin hydrochloride 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 3 and 1 times, respectively, a 2,000 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 pregestational diabetes mellitus with an HbA1c >7 and has been reported to be as high as 20 to 25% in women with an 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 HCl was not teratogenic or embyrolethal when administered to rats prior to pregnancy through the period of organogenesis at doses up to 900 mg/kg, or when administered to rabbits during the period of organogenesis at doses up to 90 mg/kg.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of metformin hydrochloride in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of metformin hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 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 DOSAGE AND ADMINISTRATION ( 2.2 ) and 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/minute 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 a biguanide that improves glucose tolerance in patients with type 2 diabetes, 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 1,000 mg (2x500 mg tablets) metformin hydrochloride extended-release tablets after a meal, the time to reach maximum plasma metformin concentration (T max ) is achieved at approximately 7 to 8 hours. In both single- and multiple-dose studies in healthy subjects, once daily 1,000 mg (2x500 mg tablets) dosing provides equivalent systemic exposure, as measured by area under the-curve (AUC), and up to 35% higher C max , of metformin relative to the immediate release given as 500 mg twice daily.
At usual clinical doses and dosing schedules of metformin, steady state plasma concentrations of metformin are reached within 24 to 48 hours and are generally <1 mcg/mL. In a two-way, single-dose, crossover study in healthy volunteers, the 1,000 mg tablet was found to be similar to two 500 mg tablets under fed conditions based on equivalent C max and AUCs for the two formulations. Single oral doses of metformin hydrochloride extended-release tablets from 500 mg to 2,500 mg resulted in less than proportional increase in both AUC and C max .
Effect of food: Low-fat and high-fat meals increased the systemic exposure (as measured by AUC) from metformin hydrochloride extended-release tablets by about 38% and 73%, respectively, relative to fasting. Both meals prolonged metformin T max by approximately 3 hours but C max was not affected. Distribution The apparent volume of distribution (V/F) of metformin following single oral doses of 850 mg metformin HCl 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 healthy 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.
Excretion Renal clearance is approximately 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.
Special Populations Renal Impairment: Following a single-dose administration of metformin hydrochloride extended-release tablets, 500 mg in subjects with mild and moderate renal impairment, the oral and renal clearance of metformin were decreased by 33% and 50% and 16% and 53%, respectively. Metformin peak and systemic exposure was 27% and 61% greater, respectively in subjects with mild renal impairment and 74% and 2.36-fold greater in subjects with moderate renal impairment as compared to healthy subjects. [see DOSAGE AND ADMINISTRATION ( 2.2 ), CONTRAINDICATIONS ( 4 ), and WARNINGS AND PRECAUTIONS ( 5.1 )] Hepatic Impairment: No pharmacokinetic studies of metformin hydrochloride extended-release tablets have been conducted in subjects with hepatic impairment, [see WARNINGS AND PRECAUTIONS ( 5.1 ) and USE IN SPECIFIC POPULATIONS ( 8.7 )] Geriatrics: Limited data from controlled pharmacokinetic studies of metformin HCl in healthy elderly subjects suggest that total plasma clearance of metformin is decreased by 35%, the half-life is prolonged by 64% and… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Metformin is a biguanide that improves glucose tolerance in patients with type 2 diabetes, 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 Metformin hydrochloride extended-release tablets USP, 500 mg are available as white to off-white, oval shaped, biconvex coated tablet, debossed with "L41" on one side and "LU" on the other side. Metformin hydrochloride extended-release tablets USP, 1,000 mg are available as white to off-white, oval shaped, biconvex coated tablet, debossed with "L42" on one side and "LU" on the other side. They are supplied as follows: Strength Package NDC Code 500 mg Bottles of 100 68180-338-01 1,000 mg Bottles of 90 68180-339-09 Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F); [see USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Metformin hydrochloride extended-release tablets, USP contains the biguanide antihyperglycemic agent metformin in the form of monohydrochloride salt. The chemical name of metformin hydrochloride is N,N-dimethylimidodicarbonimidic diamide hydrochloride. The structural formula is as shown: 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.
Metformin hydrochloride 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 hydrochloride is 6.68.
Metformin hydrochloride extended-release tablets, USP contain 500 mg or 1,000 mg of metformin hydrochloride, which is equivalent to 389.93 mg or 779.86 mg metformin, respectively. Each tablet contains ammonio methacrylate copolymer, colloidal silicon dioxide, dibutyl sebacate, hypromellose, magnesium stearate, microcrystalline cellulose, povidone and talc. Metformin hydrochloride extended-release tablets USP, 500 mg meets USP Dissolution Test 13.
FDA approved dissolution test specification differ from USP for Metformin hydrochloride extended-release tablets USP, 1000 mg. Image-01
💬 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. LUPIN and the are registered trademarks of Lupin Pharmaceuticals, Inc. Manufactured for: Lupin Pharmaceuticals, Inc.
Naples, FL 34108 United States MADE IN INDIA Revised: January 2025 ID #: 277358 Image
🍼 Nursing Mothers ▾
8.3Females and Males of Reproductive Potential Discuss the potential for unintended pregnancy with premenopausal women as therapy with metformin hydrochloride may result in ovulation in some anovulatory women.
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Absorption Following a single oral dose of 1,000 mg (2x500 mg tablets) metformin hydrochloride extended-release tablets after a meal, the time to reach maximum plasma metformin concentration (T max ) is achieved at approximately 7 to 8 hours. In both single- and multiple-dose studies in healthy subjects, once daily 1,000 mg (2x500 mg tablets) dosing provides equivalent systemic exposure, as measured by area under the-curve (AUC), and up to 35% higher C max , of metformin relative to the immediate release given as 500 mg twice daily.
At usual clinical doses and dosing schedules of metformin, steady state plasma concentrations of metformin are reached within 24 to 48 hours and are generally <1 mcg/mL. In a two-way, single-dose, crossover study in healthy volunteers, the 1,000 mg tablet was found to be similar to two 500 mg tablets under fed conditions based on equivalent C max and AUCs for the two formulations. Single oral doses of metformin hydrochloride extended-release tablets from 500 mg to 2,500 mg resulted in less than proportional increase in both AUC and C max .
Effect of food: Low-fat and high-fat meals increased the systemic exposure (as measured by AUC) from metformin hydrochloride extended-release tablets by about 38% and 73%, respectively, relative to fasting. Both meals prolonged metformin T max by approximately 3 hours but C max was not affected. Distribution The apparent volume of distribution (V/F) of metformin following single oral doses of 850 mg metformin HCl 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 healthy 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.
Excretion Renal clearance is approximately 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.
Special Populations Renal Impairment: Following a single-dose administration of metformin hydrochloride extended-release tablets, 500 mg in subjects with mild and moderate renal impairment, the oral and renal clearance of metformin were decreased by 33% and 50% and 16% and 53%, respectively. Metformin peak and systemic exposure was 27% and 61% greater, respectively in subjects with mild renal impairment and 74% and 2.36-fold greater in subjects with moderate renal impairment as compared to healthy subjects. [see DOSAGE AND ADMINISTRATION ( 2.2 ), CONTRAINDICATIONS ( 4 ), and WARNINGS AND PRECAUTIONS ( 5.1 )] Hepatic Impairment: No pharmacokinetic studies of metformin hydrochloride extended-release tablets have been conducted in subjects with hepatic impairment, [see WARNINGS AND PRECAUTIONS ( 5.1 ) and USE IN SPECIFIC POPULATIONS ( 8.7 )] Geriatrics: Limited data from controlled pharmacokinetic studies of metformin HCl in healthy elderly subjects suggest that total plasma clearance of metformin is decreased by 35%, the half-life is prolonged by 64% and C max is increased by 76%, compared to healthy young subjects.
From these data, it appears that the change in metformin pharmacokinetics with aging is primarily accounted for by a change in renal function. [see DOSAGE AND ADMINISTRATION ( 2 ) and WARNINGS AND PRECAUTIONS ( 5.1 )] Gender: In the pharmacokinetic studies in healthy volunteers, there were no important differences between male and female subjects with respect to metformin AUC and t 1/2 . However, C max for metformin was 40% higher in female subject… [Excerpted — this section continues on DailyMed.]
🔬 Clinical Studies ▾
14 CLINICAL STUDIES In a multicenter, randomized, double-blind, active-controlled, dose-ranging, parallel group study conducted in patients type 2 diabetes mellitus, metformin hydrochloride extended-release tablets 1,500 mg once daily, metformin hydrochloride extended-release tablets 1,500 per day in divided doses (500 mg in the morning and 1,000 mg in the evening), and metformin hydrochloride extended-release tablets 2,000 mg once daily were compared to immediate-release metformin HCl tablets 1,500 mg per day in divided doses (500 mg in the morning and 1,000 mg in the evening).
This study included patients (n = 338) who were newly diagnosed with diabetes, patients treated only with diet and exercise, patients treated with a single antidiabetic medication (sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, or meglitinides), and patients (n = 368) receiving metformin HCl tablets up to 1,500 mg/day plus a sulfonylurea at a dose equal to or less than one-half the maximum dose. Patients who were enrolled on monotherapy or combination antidiabetic therapy underwent a 6-week washout.
Patients randomized to metformin hydrochloride extended-release tablets began titration from 1,000 mg/day up to their assigned treatment dose over 3 weeks. Patients randomized to immediate-release metformin initiated 500 mg twice daily for 1 week followed by 500 mg with breakfast and 1,000 mg with dinner for the second week. The 3-week treatment period was followed by an additional 21-week period at the randomized dose.
The results are presented in Table 4. Table 5: Mean Changes from Baseline in HbA1c and Fasting Plasma Glucose at Week 24 Comparing Metformin Hydrochloride Extended-Release Tablets versus Metformin HCl Tablets* in Patients with Type 2 Diabetes Mellitus * Immediate-release metformin HCl tablets Metformin Hydrochloride Extended-Release Tablets Metformin HCl Tablets* 1,500 mg in Divided Doses (n = 174) 1,500 mg Once Daily (n = 178) 1,500 mg in Divided Doses (n = 182) 2,000 mg Once Daily (n =172) HbA1c (%), N 169 175 159 170 Baseline 8.2 8.5 8.3
8.7Mean Change at Final Visit -0.7 -0.7 -1.1 -0.7 Mean Difference from Metformin HCl Tablets* (98.4% CI) 0 (-0.3, 0.3) 0 (-0.3, 0.3) -0.4 (-0.7, -0.1) N/A Fasting Plasma Glucose (mg/dL), N 175 179 170 172 Baseline 190 192.3 184 197 Mean Change at Final Visit -39 -32 -42 -32 Mean Difference from Metformin HCl Tablets* (95% CI) -6 (-15, 2) 0 (-8, 9) -10 (-19, -1) N/A Mean baseline body weight was 88.2 kg, 90.5 kg, 87.7 kg and 88.7 kg in the metformin hydrochloride extended-release tablets 1,500 mg once daily, metformin hydrochloride extended-release tablets 1,500 mg in divided doses, metformin hydrochloride extended-release tablets 2,000 mg once daily and metformin HCl tablets 1,500 mg in divided doses arms, respectively.
Mean change in body weight from baseline to week 24 was -0.9 kg, -0.7 kg, -1.1 kg, and -0.9 kg in the metformin hydrochloride extended-release tablets 1,500 mg once daily, metformin hydrochloride extended-release tablets 1,500 mg in divided doses, metformin hydrochloride extended-release tablets 2,000 mg once daily and metformin HCl tablets 1,500 mg in divided doses arms, respectively. A double-blind, randomized, placebo-controlled (glyburide add-on) multicenter study enrolled patients with type 2 diabetes mellitus who were newly diagnosed or treated with diet and exercise (n = 144), or who were receiving monotherapy with metformin, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, or meglitinides, or treated with combination therapy consisting of metformin HCl/glyburide at doses up to 1,000 mg metformin + 10 mg glyburide per day (or equivalent doses of glipizide or glimepiride up to half the maximum therapeutic dose) (n = 431).
All patients were stabilized on glyburide for a 6-week run-in period, and then randomized to 1 of 4 treatments: placebo + glyburide (glyburide alone); metformin hydrochloride extended-release tablets 1,500 mg once a day + glyburide… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term carcinogenicity studies have been performed in Sprague Dawley rats at doses of 150, 300, and 450 mg/kg/day in males and 150, 450, 900, and 1,200 mg/kg/day in females. These doses are approximately 2, 4, and 8 times in males, and 3, 7, 12, and 16 times in females of the maximum recommended human daily dose of 2,000 mg based on body surface area comparisons. No evidence of carcinogenicity with metformin was found in either male or female rats.
A carcinogenicity study was also performed in Tg.AC transgenic mice at doses up to 2,000 mg applied dermally. No evidence of carcinogenicity was observed in male or female mice. Genotoxicity assessments in the Ames test, gene mutation test (mouse lymphoma cells), chromosomal aberrations test (human lymphocytes) and in vivo mouse micronucleus tests were negative.
Fertility of male or female rats was not affected by metformin when administered at doses up to 600 mg/kg/day, which is approximately 3 times the maximum recommended human daily dose based on body surface area comparisons.
📄 Patient Package Insert ▾
PATIENT INFORMATION Metformin Hydrochloride Extended-Release Tablets USP (met-FOR-min HYE-droe-KLOR-ide) What is the most important information I should know about metformin hydrochloride extended-release tablets? Metformin hydrochloride extended-release tablets can cause serious side effects, 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 buildup of lactic acid in the blood) that can cause death.
Lactic acidosis is a medical emergency and must be treated in the hospital. Stop taking metformin hydrochloride extended-release tablets and call your doctor 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 unexplained stomach or intestinal problems with nausea and vomiting, or diarrhea have unusual sleepiness or sleep longer than usual 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 severe kidney problems.
See "Do not take metformin hydrochloride extended-release tablets if you" have liver problems. 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 or other procedure for which you need to restrict the amount of food and liquid you eat and drink. have congestive heart failure. have a heart attack, severe infection, or stroke. are 65 years of age or older.
Tell your doctor if you have any of the problems in the list above. Tell your doctor that you are taking metformin hydrochloride extended-release tablets before you have surgery or x-ray tests. Your doctor may need to stop metformin hydrochloride extended-release tablets for a while if you have surgery or certain x-ray tests.
Metformin hydrochloride extended-release tablets can have other serious side effects. See "What are the possible side effects of metformin hydrochloride extended-release tablets?" . What is metformin hydrochloride extended-release tablet?
Metformin hydrochloride extended-release tablet is a prescription medicine that contains metformin hydrochloride. Metformin hydrochloride extended-release tablet is used with diet and exercise to help control high blood sugar (hyperglycemia) in adults with type 2 diabetes. It is not known if metformin hydrochloride extended-release tablet is safe and effective in children.
Do not take metformin hydrochloride extended-release tablets if you: have severe 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. See the end of this leaflet for a list of ingredients in metformin hydrochloride extended-release tablets. have a condition called metabolic acidosis or diabetic ketoacidosis (increased ketones in your blood or urine). Before taking metformin hydrochloride extended-release tablets tell your doctor about all of your medical conditions, including if you: have a history or risk for diabetic ketoacidosis.
See "Do not take metformin hydrochloride extended-release tablets if you:". have kidney problems. have liver problems. have heart problems, including congestive heart failure. are 65 years of age or older. drink alcohol very often, or drink a lot of alcohol in short-term "binge" drinking. are taking insulin or a sulfonylurea medicine. are pregnant or plan to become pregnant. It is not known if metformin hydrochloride extended-release tablets can harm your unborn baby. If you are pregnant, talk with your doc… [Excerpted — this section continues on DailyMed.]
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL Metformin Hydrochloride Extended-Release Tablets USP 500 mg Bottle Pack: 100 Tablets NDC: 68180-338-01 Metformin Hydrochloride Extended-Release Tablets USP 1000 mg Bottle Pack: 90 Tablets NDC: 68180-339-09 image 2 Image-03