Metformin Hydrochloride 500 mg Tablet, Extended Release, 1,000-count — NDC 42385-977-11 (Billing 42385-0977-11)
This is a package of 1,000 tablets of Metformin Hydrochloride 500 mg Tablet, Extended Release from Laurus Labs Limited, marketed since Oct 2023 and currently FDA-listed; retail pharmacies pay about $0.0284 per tablet (NADAC). It is the main listing for this product, which comes in 7 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): 046754
- GCN: 89863
- 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 | $0.028 | $28.40 / 1000 tablets |
| Medicaid paysCMS SDUD · 12 mo | $0.0965 | $96.50 / 1000 tablets |
| Medicare drug plans payPart D · Q2 2026 | $0.1129 | $112.90 / 1000 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 |
|---|---|---|---|---|---|---|
| 42385-0977-01 42385-977-01 | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE | $0.0284 / ea | $2.84 | 2023-10-06 | — | Active |
| 42385-0977-05 42385-977-05 | 500 TABLET, EXTENDED RELEASE in 1 BOTTLE | $0.0284 / ea | $14.19 | 2023-10-06 | — | Active |
| 42385-0977-11 You're viewing this Main listing | 1000 TABLET, EXTENDED RELEASE in 1 BOTTLE | $0.0284 / ea | $28.38 | 2023-10-06 | — | Active |
| 42385-0977-18 42385-977-18 | 180 TABLET, EXTENDED RELEASE in 1 BOTTLE | — | — | 2023-10-06 | — | Active |
| 42385-0977-30 42385-977-30 | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE | — | — | 2023-10-06 | — | Active |
| 42385-0977-72 42385-977-72 | 15 BLISTER PACK in 1 CARTON / 10 TABLET, EXTENDED RELEASE in 1 BLISTER PACK | — | — | 2023-10-06 | — | Active |
| 42385-0977-90 42385-977-90 | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE | $0.0284 / ea | $2.55 | 2023-10-06 | — | Active |
This pack effectively ties for the lowest per-ea cost of the 4 priced pack sizes ($0.0284 NADAC).
In Medicaid, this is the most-dispensed pack of this product — about 48% 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 42385-0977-30?
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 29300-0389-01 | Unichem | 100 tablets | $0.028 | AB1 | Availability likely | — |
| Metformin Hydrochloride 500 mgthis 42385-0977-11 | Laurus | 1000 tablets | $0.028 | AB1 | Availability likely | — |
| Metformin Hydrochloride 500 mg 42806-0632-01 | Epic | 100 tablets | $0.028 | AB1 | Availability likely | — |
| Metformin Hydrochloride Extended Release 500 mg 49483-0623-01 | TIME | 100 tablets | $0.028 | AB1 | Availability likely | — |
| Metformin Hydrochloride 500 mg 50268-0550-15 | AvPAK | 1 tablet | $0.028 | AB1 | Availability likely | — |
| Metformin Hydrochloride 500 mg 67877-0159-01 | Ascend | 100 tablets | $0.028 | AB1 | Availability likely | — |
| Metformin Hydrochloride 500 mg 67877-0413-01 | Ascend | 100 tablets | $0.028 | AB1 | Availability likely | — |
| Metformin Hydrochloride 500 mg 68094-0904-50 | Precision | 100 tablets | $0.028 | AB1 | Availability likely | — |
| Metformin 500 mg 68645-0595-59 | Legacy | 60 tablets | $0.028 | AB1 | Availability likely | — |
| Metformin Hydrochloride Er 500 mg 69315-0410-01 | Leading | 100 tablets | $0.028 | AB1 | Availability likely | — |
| Metformin 500 mg 70010-0491-01 | Granules | 100 tablets | $0.028 | AB1 | Availability likely | — |
| Metformin ER 500 mg 82009-0117-10 | Quallent | 1000 tablets | $0.028 | AB1 | Availability likely | — |
| Metformin Hydrochloride 500 mg 82009-0180-05 | Quallent | 500 tablets | $0.028 | AB1 | Availability likely | — |
| Metformin Hydrochloride 500 mg 62756-0142-01 | Sun | 100 tablets | $0.029 | — | FDA listed | +2% |
| Metformin hydrochloride 500 mg 33342-0239-11 | Macleods | 100 tablets | $0.031 | AB1 | FDA listed | +10% |
| Metformin Hydrochloride 500 mg 51224-0007-50 | TAGI | 100 tablets | $0.031 | AB1 | FDA listed | +10% |
| Metformin Hydrochloride 500 mg 69367-0412-60 | Westminster | 60 tablets | $0.164 | AB2 | Availability likely | +479% |
| Metformin hydrochloride 500 mg 27241-0188-60 | Ajanta | 60 tablets | $0.164 | AB2 | Availability likely | +479% |
| Metformin Hydrochloride 500 mg 59651-0042-60 | Aurobindo | 60 tablets | $0.164 | AB2 | Availability likely | +479% |
| Metformin Hydrochloride 500 mg 42571-0333-01 | Micro | 100 tablets | $0.271 | AB3 | Availability likely | +855% |
| Metformin Hydrochloride 500 mg 68180-0338-01 | Lupin | 100 tablets | $0.271 | AB3 | Availability likely | +855% |
| Metformin Hydrochloride 500 mg 70010-0496-01 | Granules | 100 tablets | $0.271 | AB3 | Availability likely | +855% |
| Metformin hydrochloride 500 mg 27241-0240-01 | Ajanta | 100 tablets | $0.271 | AB3 | Availability likely | +855% |
| Metformin Hydrochloride 500 mg 68462-0520-01 | GLENMARK | 100 tablets | $0.271 | AB3 | Availability likely | +855% |
| Metformin hydrochloride 500 mg 68682-0021-50 | Oceanside | 100 tablets | $0.402 | — | FDA listed | +1316% |
| Glumetza 500 mg 68012-0004-50 | Santarus, | 100 tablets | $49.542 | — | FDA listed | +174468% |
| Metformin Hydrochloride 500 mg 00615-8289-39 | NCS | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 10135-0823-05 | Marlex | 500 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride Extended-Release 500mg 500 mg 17224-0311-28 | Calvin | 28 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 25000-0101-03 | MARKSANS | 30 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 42291-0825-10 | AvKARE | 1000 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 42708-0201-60 | QPharma | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-1494-00 | A-S | 60 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 500 mg 50090-6515-00 | A-S | 60 tablets | — | AB1 | FDA listed | — |
| Metformin 500 mg 50090-6516-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-7116-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-7576-00 | A-S | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-7577-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-7579-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 50090-7918-00 | A-S | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride Extended Release 500 mg 51655-0555-96 | Northwind | 180 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 59651-0548-25 | Aurobindo | 25000 tablets | — | AB1 | FDA listed | — |
| Metformin ER 500 mg 62207-0491-31 | Granules | 5000 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 63187-0779-00 | Proficient | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 65162-0178-03 | Amneal | 30 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride 500 mg 65841-0027-01 | Zydus | 100 tablets | — | AB1 | Discontinued | — |
| Metformin Hydrochloride 500 mg 65841-0809-01 | Zydus | 100 tablets | — | AB | FDA listed | — |
| Metformin 500 mg 67046-0437-03 | Coupler | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 67296-1701-06 | RedPharm | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride Extended Release 500 mg 68071-3111-02 | NuCare | 120 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 68788-8814-01 | Preferred | 100 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 500 mg 69238-2125-01 | Amneal | 100 tablets | — | — | FDA listed | — |
| Metformin 500 mg 70518-4370-00 | REMEDYREPACK | 30 tablets | — | AB1 | 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 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 71335-0886-01 | Bryant | 60 tablets | — | AB1 | FDA listed | — |
| Metformin 500 mg 71335-2354-01 | Bryant | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71335-2568-01 | Bryant | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71335-9683-01 | Bryant | 60 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 500 mg 71610-0613-60 | Aphena | 90 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 71610-0652-30 | Aphena | 30 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride 500 mg 71610-0837-30 | Aphena | 30 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 71610-0858-30 | Aphena | 30 tablets | — | AB1 | FDA listed | — |
| Metformin 500 mg 72162-2424-00 | Bryant | 1000 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride Extended Release 500 mg 72189-0064-30 | direct | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 72189-0150-30 | direct | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 72578-0035-01 | Viona | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 72664-0227-01 | VGYAAN | 100 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride Extended Release 500 mg 72789-0009-30 | PD-Rx | 30 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 72789-0105-01 | PD-Rx | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 72789-0400-01 | PD-Rx | 100 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 72789-0454-60 | PD-Rx | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 72789-0455-30 | PD-Rx | 30 tablets | — | AB1 | FDA listed | — |
| Metformin hydrochloride 500 mg 76385-0128-01 | UNICHEM | 100 tablets | — | AB1 | FDA listed | — |
| Metformin 500 mg 82804-0147-30 | Proficient | 30 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 82804-0195-60 | Proficient | 60 tablets | — | AB1 | FDA listed | — |
| Metformin Hydrochloride 500 mg 43547-0503-10 | Solco | 100 tablets | — | AB3 | FDA listed | — |
| Metformin Hydrochloride 500 mg 47335-0305-18 | Sun | 1000 tablets | — | — | Discontinued | — |
| Glumetza 500 mg 68012-0002-13 | Santarus, | 100 tablets | — | — | FDA listed | — |
| Metformin Hydrochloride 500 mg 68180-0336-01 | Lupin | 100 tablets | — | AB2 | FDA listed | — |
| Metformin Hydrochloride 500 mg 62207-0496-47 | Granules | 500 tablets | — | AB3 | FDA listed | — |
| Metformin hydrochloride 500 mg 68071-1419-02 | NuCare | 20 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.
💡 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 VM7F0B23ZI
Hypromellose 2208 is a plant-derived thickening agent that forms a protective coating on tablets and capsules. It slows down how quickly the medicine dissolves, controlling drug release into your body.
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UNII 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.
3 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.- 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 Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL [see Warnings and Precautions (5.1) ].
Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, hepatic impairment, and mitochondrial diseases [see Warnings and Precautions (5.1) ]. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided [see Dosage and Administration (2.3) , (2.7), Contraindications (4) , Warnings and Precautions (5.1) ].
If metformin-associated lactic acidosis is suspected, immediately discontinue metformin hydrochloride 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, hepatic impairment, and mitochondrial diseases.
Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the Full Prescribing Information. ( 5.1 ) ● If lactic acidosis is suspected, discontinue metformin hydrochloride and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.
( 5.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Metformin hydrochloride tablets, USP 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 tablets, USP 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 Adult Dosage for Metformin Hydrochloride Tablets: Starting dose: 500 mg orally twice a day or 850 mg once a day, with meals ( 2.1 ) Increase the dose in increments of 500 mg weekly or 850 mg every 2 weeks, up to a maximum dose of 2,550 mg per day, given in divided doses ( 2.1 ) Doses above 2,000 mg may be better tolerated given 3 times a day with meals ( 2.1 ) Pediatric Dosage for Metformin Hydrochloride Tablets : Starting dose: 500 mg orally twice a day, with meals ( 2.2 ) Increase dosage in increments of 500 mg weekly up to a maximum of 2,000 mg per day, given in divided doses twice daily ( 2.2 ) Renal Impairment: Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR) ( 2.3 ) Do not use in patients with eGFR below 30 mL/minute/1.73 m 2 ( 2.3 ) Initiation is not recommended in patients with eGFR between 30 to 45 mL/minute/1.73 m 2 ( 2.3 ) Assess risk/benefit of continuing if eGFR falls below 45 mL/minute/1.73 m 2 ( 2.3 ) Discontinue if eGFR falls below 30 mL/minute/1.73 m 2 ( 2.3 ) Discontinuation for Iodinated Contrast Imaging Procedures: Metformin hydrochloride tablets may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures ( 2.4 )
2.1Adult Dosage Metformin Hydrochloride Tablets The recommended starting dose of metformin hydrochloride tablets is 500 mg orally twice a day or 850 mg once a day, given with meals. Increase the dose in increments of 500 mg weekly or 850 mg every 2 weeks on the basis of glycemic control and tolerability, up to a maximum dose of 2,550 mg per day, given in divided doses. Doses above 2,000 mg may be better tolerated given 3 times a day with meals.
2.2Pediatric Dosage for Metformin Hydrochloride Tablets The recommended starting dose of metformin hydrochloride tablets for pediatric patients 10 years of age and older is 500 mg orally twice a day, given with meals. Increase dosage in increments of 500 mg weekly on the basis of glycemic control and tolerability, up to a maximum of 2,000 mg per day, given in divided doses twice daily.
2.3Recommendations for Use in Renal Impairment • Assess renal function prior to initiation of metformin hydrochloride tablets and periodically thereafter. • Metformin hydrochloride tablets are contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m 2 . • Initiation of metformin hydrochloride tablets in patients with an eGFR between 30 to 45 mL/minute/1.73 m 2 is not recommended. • In patients taking metformin hydrochloride tablets whose eGFR later falls below 45 mL/min/1.73 m 2 , assess the benefit risk of continuing therapy. • Discontinue metformin hydrochloride tablets if the patient’s eGFR later falls below 30 mL/minute/1.73 m 2 [see Warnings and Precautions (5.1) ].
2.4Discontinuation for Iodinated Contrast Imaging Procedures Discontinue metformin hydrochloride tablets at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m 2 ; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart metformin hydrochloride tablets if renal function is stable.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Metformin Hydrochloride Tablets, USP are available as: Tablets: 500 mg white to off white, round, biconvex, flavored, film coated tablets with 'LL' debossed on one side and plain on the other side. Tablets: 850 mg white to off white, capsule shaped, biconvex, flavored, film coated tablets with 'L06' debossed on one side and plain on the other side. Tablets: 1,000 mg white to off white, oval, biconvex, flavored, film coated tablets, with score line on both sides, with 'L' and '11' debossed on either side of score line on one side.
Metformin hydrochloride tablets, USP: 500 mg, 850 mg, and 1,000 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) [see Warnings and Precautions (5.1) ]. Hypersensitivity to metformin. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) ( 4 , 5.1 ) Hypersensitivity to metformin ( 4 ) Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Lactic Acidosis: See boxed warning. ( 5.1 ) Vitamin B 12 Deficiency: Metformin may lower vitamin B 12 levels. Measure hematological parameters annually and vitamin B 12 at 2 to 3 year intervals and manage any abnormalities.
( 5.2 ) Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Increased risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. Lower dose of insulin or insulin secretagogue may be required ( 5.3 )
5.1Lactic Acidosis There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate: pyruvate ratio; metformin plasma levels were generally >5 mcg/mL.
Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of metformin hydrochloride. In metformin hydrochloride 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 and report these symptoms to their healthcare provider. For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below: • Renal impairment —The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment.
The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney. Clinical recommendations based upon the patient’s renal function include [see Dosage and Administration (2.1) , Clinical Pharmacology (12.3) ]: o Before initiating metformin hydrochloride, obtain an estimated glomerular filtration rate (eGFR). o Metformin hydrochloride is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 [see Contraindications (4) ]. o Initiation of metformin hydrochloride is not recommended in patients with eGFR between 30 to 45 mL/min/1.73 m 2 . o Obtain an eGFR at least annually in all patients taking metformin hydrochloride.
In patients at risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently. o In patients taking metformin hydrochloride 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 with specific drugs may increase the risk of metformin-associated lactic acidosis: those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance, or increase metformin accumulation.
Consider more frequent monitoring of patients. • Age 65 or greater — The risk of metformin-associated lactic acidosis increases with the patient’s age because elderly patients have a greater likelihood of having hepatic, renal, or cardiac impai… [Excerpted — this section continues on DailyMed.]
🤒 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, 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 Laurus Generics Inc. at 1-833-3-LAURUS (1-833-352-8787) 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 In a U.S. clinical trial of metformin hydrochloride in patients with type 2 diabetes mellitus, a total of 141 patients received metformin hydrochloride up to 2,550 mg per day. Adverse reactions reported in greater than 5% of metformin hydrochloride treated patients and that were more common than in placebo-treated patients, are listed in Table 1.
Table 1: Adverse Reactions from a Clinical Trial of Metformin Hydrochloride Occurring >5% and More Common than Placebo in Patients with Type 2 Diabetes Mellitus Metformin Hydrochloride (n=141) Placebo (n=145) Diarrhea 53% 12% Nausea/Vomiting 26% 8% Flatulence 12% 6% Asthenia 9% 6% Indigestion 7% 4% Abdominal Discomfort 6% 5% Headache 6% 5% Diarrhea led to discontinuation of metformin hydrochloride in 6% of patients. Additionally, the following adverse reactions were reported in ≥1% to ≤5% of metformin hydrochloride treated patients and were more commonly reported with metformin hydrochloride than placebo: abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation.
In metformin hydrochloride clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of patients. Pediatric Patients In clinical trials with metformin hydrochloride in pediatric patients with type 2 diabetes mellitus, the profile of adverse reactions was similar to that observed in adults.
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 3 presents clinically significant drug interactions with metformin hydrochloride. Table 3: Clinically Significant Drug Interactions with Metformin Hydrochloride 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 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 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. 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. Insulin Secretagogues or Insulin Clinical Impact: Coadministration of metformin hydrochloride 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, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin hydrochloride, 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 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 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 Metformin Hydr… [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 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 Metformin Hydrochloride The safety and effectiveness of metformin hydrochloride for the treatment of type 2 diabetes mellitus have been established in pediatric patients 10 to 16 years old. Safety and effectiveness of metformin hydrochloride have not been established in pediatric patients less than 10 years old. Use of metformin hydrochloride in pediatric patients 10 to 16 years old for the treatment of type 2 diabetes mellitus is supported by evidence from adequate and well-controlled studies of metformin hydrochloride in adults with additional data from a controlled clinical study in pediatric patients 10 to 16 years old with type 2 diabetes mellitus, which demonstrated a similar response in glycemic control to that seen in adults [see Clinical Studies (14.1) ] .
In this study, adverse reactions were similar to those described in adults. A maximum daily dose of 2,000 mg of metformin hydrochloride is recommended. [See Dosage and Administration (2.2) .]
🧓 Geriatric Use ▾
8.5Geriatric Use Controlled clinical studies of metformin hydrochloride did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis. Assess renal function more frequently in elderly patients [see Warnings and Precautions (5.1) ].
🆘 Overdosage ▾
10 OVERDOSAGE Overdose of metformin 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 The absolute bioavailability of a metformin hydrochloride 500 mg tablet given under fasting conditions is approximately 50% to 60%. Studies using single oral doses of metformin hydrochloride 500 to 1,500 mg and 850 to 2,550 mg, indicate that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption rather than an alteration in elimination. At usual clinical doses and dosing schedules of metformin hydrochloride, steady state plasma concentrations of metformin are reached within 24 to 48 hours and are generally <1 mcg/mL.
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. Distribution The apparent volume of distribution (V/F) of metformin following single oral doses of metformin hydrochloride 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 4) 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 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 3) [See Dosage and Administration (2.3) , Contraindications (4) , Warnings and Precautions (5.1) and Use in Specific Populations (8.6) ]. Hepatic Impairment No pharmacokinetic studies of metformin have been conducted in patients 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 hydrochloride in healthy elderly subjects suggest that total plasma clearance of metformin is decreased, the half-life is prolonged, and C max is increased, compared to healthy young subjects.
It appears that the change in metformin pharmacokinetics with aging is primarily accounted for by a change in renal function (see Table 4). [See Warnings and Precautions (5.1) and Use in Specific Populations (8.5) ]. Table 4: Select Mean (±S.D.) Metformin Pharmacokinetic Parameters Following Single or Multiple Oral Doses of Metformin Hydrochloride a All doses given fasting except the first 18 doses of the multiple dose studies b Peak plasma concentration c Time to peak plasma concentration d Combined results (average means) of five studies: mean age 32… [Excerpted — this section continues on DailyMed.]
🧬 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 Tablets, USP are supplied in the following strengths and package configurations: Metformin Hydrochloride Tablets, USP 500 mg are supplied as white to off white, round, biconvex, flavored, film coated tablets with ‘LL’ debossed on one side and plain on the other side. Bottles of 90 NDC 42385-947-90 Bottles of 100 NDC 42385-947-01 Bottles of 180 NDC 42385-947-18 Bottles of 500 NDC 42385-947-05 Bottles of 1,000 NDC 42385-947-11 Carton with 100 (10×10) Unit-Dose Tablets NDC 42385-947-19 Metformin Hydrochloride Tablets, USP 850 mg are supplied as white to off white, capsule shaped, biconvex, flavored, film coated tablets with ‘L06’ debossed on one side and plain on the other side.
Bottles of 90 NDC 42385-948-90 Bottles of 100 NDC 42385-948-01 Bottles of 180 NDC 42385-948-18 Bottles of 500 NDC 42385-948-05 Bottles of 1,000 NDC 42385-948-11 Carton with 100 (10×10) Unit-Dose Tablets NDC 42385-948-19 Metformin Hydrochloride Tablets, USP 1,000 mg are supplied as white to off white, oval, biconvex, flavored, film coated tablets, with score line on both sides, with ‘L’ and ‘11’ debossed on either side of score line on one side. Bottles of 60 NDC 42385-949-60 Bottles of 90 NDC 42385-949-90 Bottles of 100 NDC 42385-949-01 Bottles of 180 NDC 42385-949-18 Bottles of 500 NDC 42385-949-05 Bottles of 1,000 NDC 42385-949-11 Carton with 100 (10×10) Unit-Dose Tablets NDC 42385-949-19
16.2Storage Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Dispense in light-resistant containers.
📋 Description ▾
11 DESCRIPTION Metformin hydrochloride 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, USP 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 tablets, USP contain 500 mg, 850 mg, or 1,000 mg of metformin hydrochloride, which is equivalent to 389.93 mg, 662.88 mg, 779.86 mg metformin base, respectively. Each tablet contains the inactive ingredients colloidal silicon dioxide, croscarmellose sodium, magnesium stearate and povidone. In addition, the tablet coating material of 500 mg, 850 mg and 1,000 mg tablets contain hypromellose, polyethylene glycol 3350, polyvinyl alcohol, talc, titanium dioxide and artificial blackberry flavor. metformin-structure.jpg
💬 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 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 tablets. Instruct patients to inform their doctor that they are taking metformin hydrochloride 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 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 tablets [see Warnings and Precautions (5.2) ] . F emales of Reproductive Age: Inform females that treatment with metformin hydrochloride tablets may result in ovulation in some premenopausal anovulatory women which may lead to unintended pregnancy [see Use in Specific Populations (8.3) ].
Manufactured for: Laurus Generics Inc. 400 Connell Drive Suite 5200 Berkeley Heights, NJ 07922 Manufactured by: Laurus Labs Limited Anakapalli-531011 India
🍼 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 The absolute bioavailability of a metformin hydrochloride 500 mg tablet given under fasting conditions is approximately 50% to 60%. Studies using single oral doses of metformin hydrochloride 500 to 1,500 mg and 850 to 2,550 mg, indicate that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption rather than an alteration in elimination. At usual clinical doses and dosing schedules of metformin hydrochloride, steady state plasma concentrations of metformin are reached within 24 to 48 hours and are generally <1 mcg/mL.
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. Distribution The apparent volume of distribution (V/F) of metformin following single oral doses of metformin hydrochloride 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 4) 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 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 3) [See Dosage and Administration (2.3) , Contraindications (4) , Warnings and Precautions (5.1) and Use in Specific Populations (8.6) ]. Hepatic Impairment No pharmacokinetic studies of metformin have been conducted in patients 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 hydrochloride in healthy elderly subjects suggest that total plasma clearance of metformin is decreased, the half-life is prolonged, and C max is increased, compared to healthy young subjects.
It appears that the change in metformin pharmacokinetics with aging is primarily accounted for by a change in renal function (see Table 4). [See Warnings and Precautions (5.1) and Use in Specific Populations (8.5) ]. Table 4: Select Mean (±S.D.) Metformin Pharmacokinetic Parameters Following Single or Multiple Oral Doses of Metformin Hydrochloride a All doses given fasting except the first 18 doses of the multiple dose studies b Peak plasma concentration c Time to peak plasma concentration d Combined results (average means) of five studies: mean age 32 years (range 23 to 59 years) e Kinetic study done following dose 19, given fasting f Elderly subjects, mean age 71 years (range 65 to 81 years) g CLcr = creatinine clearance normalized to body surface area of 1.73 m 2 Subject Groups: Metformin Hydrochloride dose a (number of subjects) C max b (mcg/mL) T max c (hrs) Renal Clearance (mL/min) Healthy, nondiabetic adults: 500 mg single dose (24) 850 mg single dose (74) d 850 mg three times daily for 19 doses e (9) 1.03 (±0.33) 1.60 (±0.38) 2.01 (±0.42) 2.75 (±0.81) 2.64 (±0.82) 1.79 (±0.9… [Excerpted — this section continues on DailyMed.]
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Metformin Hydrochloride Adult Clinical Studies A double-blind, placebo-controlled, multicenter U.S. clinical trial involving obese patients with type 2 diabetes mellitus whose hyperglycemia was not adequately controlled with dietary management alone (baseline fasting plasma glucose [FPG] of approximately 240 mg/dL) was conducted. Patients were treated with metformin hydrochloride (up to 2,550 mg/day) or placebo for 29 weeks. The results are presented in Table 7.
Table 7: Mean Change in Fasting Plasma Glucose and HbA1c at Week 29 Comparing Metformin Hydrochloride vs Placebo in Patients with Type 2 Diabetes Mellitus * Not statistically significant Metformin Hydrochloride (n=141) Placebo (n=145) p-Value FPG (mg/dL) Baseline Change at FINAL VISIT 241.5 –53.0 237.7
6.3NS* 0.001 Hemoglobin A1c (%) Baseline Change at FINAL VISIT 8.4 –1.4 8.2
0.4NS* 0.001 Mean baseline body weight was 201 lbs and 206 lbs in the metformin hydrochloride and placebo arms, respectively. Mean change in body weight from baseline to week 29 was -1.4 lbs and -2.4 lbs in the metformin hydrochloride and placebo arms, respectively. A 29-week, double-blind, placebo-controlled study of metformin hydrochloride and glyburide, alone and in combination, was conducted in obese patients with type 2 diabetes mellitus who had failed to achieve adequate glycemic control while on maximum doses of glyburide (baseline FPG of approximately 250 mg/dL).
Patients randomized to the combination arm started therapy with metformin hydrochloride 500 mg and glyburide 20 mg. At the end of each week of the first 4 weeks of the trial, these patients had their dosages of metformin hydrochloride increased by 500 mg if they had failed to reach target fasting plasma glucose. After week 4, such dosage adjustments were made monthly, although no patient was allowed to exceed metformin hydrochloride 2,500 mg.
Patients in the metformin hydrochloride only arm (metformin plus placebo) discontinued glyburide and followed the same titration schedule. Patients in the glyburide arm continued the same dose of glyburide. At the end of the trial, approximately 70% of the patients in the combination group were taking metformin hydrochloride 2,000 mg/glyburide 20 mg or metformin hydrochloride 2,500 mg/glyburide 20 mg.
The results are displayed in Table 8. Table 8: Mean Change in Fasting Plasma Glucose and HbA1c at Week 29 Comparing Metformin Hydrochloride/Glyburide (Comb) vs Glyburide (Glyb) vs Metformin Hydrochloride (MET): in Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Glyburide * Not statistically significant Comb (n=213) Glyb (n=209) MET (n=210) p-Values Glyb vs Comb MET vs Comb MET vs Glyb Fasting Plasma Glucose (mg/dL) Baseline 250.5 247.5 253.9 NS* NS* NS* Change at FINAL VISIT –63.5 13.7 –0.9 0.001 0.001 0.025 Hemoglobin A1c (%) Baseline 8.8 8.5
8.9NS* NS* 0.007 Change at FINAL VISIT –1.7 0.2 –0.4 0.001 0.001 0.001 Mean baseline body weight was 202 lbs, 203 lbs, and 204 lbs in the metformin hydrochloride/glyburide, glyburide, and metformin hydrochloride arms, respectively. Mean change in body weight from baseline to week 29 was 0.9 lbs, -0.7 lbs, and -8.4 lbs in the metformin hydrochloride/glyburide, glyburide, and metformin hydrochloride arms, respectively. Pediatric Clinical Studies A double-blind, placebo-controlled study in pediatric patients aged 10 to 16 years with type 2 diabetes mellitus (mean FPG 182.2 mg/dL), treatment with metformin hydrochloride (up to 2,000 mg/day) for up to 16 weeks (mean duration of treatment 11 weeks) was conducted.
The results are displayed in Table 9. Table 9: Mean Change in Fasting Plasma Glucose at Week 16 Comparing Metformin Hydrochloride vs Placebo in Pediatric Patients a with Type 2 Diabetes Mellitus a Pediatric patients mean age 13.8 years (range 10 to16 years) Metformin Hydrochloride Placebo p-Value FPG (mg/dL) Baseline Change at FINAL VISIT (n=37) 162.4 –42.9 (n=36) 192.3 21.4 <0.001 Mean baseline bo… [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 rats (dosing duration of 104 weeks) and mice (dosing duration of 91 weeks) at doses up to and including 900 mg/kg/day and 1,500 mg/kg/day, respectively. These doses are both approximately 3 times the maximum recommended human daily dose of 2,550 mg based on body surface area comparisons. No evidence of carcinogenicity with metformin was found in either male or female mice.
Similarly, there was no tumorigenic potential observed with metformin in male rats. There was, however, an increased incidence of benign stromal uterine polyps in female rats treated with 900 mg/kg/day. There was no evidence of a mutagenic potential of metformin in the following in vitro tests: Ames test ( S. typhimurium ), gene mutation test (mouse lymphoma cells), or chromosomal aberrations test (human lymphocytes).
Results in the in vivo mouse micronucleus test were also negative. Fertility of male or female rats was unaffected by metformin when administered at doses as high as 600 mg/kg/day, which is approximately 2 times the maximum recommended human daily dose of 2,550 mg based on body surface area comparisons.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term carcinogenicity studies have been performed in rats (dosing duration of 104 weeks) and mice (dosing duration of 91 weeks) at doses up to and including 900 mg/kg/day and 1,500 mg/kg/day, respectively. These doses are both approximately 3 times the maximum recommended human daily dose of 2,550 mg based on body surface area comparisons. No evidence of carcinogenicity with metformin was found in either male or female mice.
Similarly, there was no tumorigenic potential observed with metformin in male rats. There was, however, an increased incidence of benign stromal uterine polyps in female rats treated with 900 mg/kg/day. There was no evidence of a mutagenic potential of metformin in the following in vitro tests: Ames test ( S. typhimurium ), gene mutation test (mouse lymphoma cells), or chromosomal aberrations test (human lymphocytes).
Results in the in vivo mouse micronucleus test were also negative. Fertility of male or female rats was unaffected by metformin when administered at doses as high as 600 mg/kg/day, which is approximately 2 times the maximum recommended human daily dose of 2,550 mg based on body surface area comparisons.
📄 Patient Package Insert ▾
PATIENT INFORMATION Metformin Hydrochloride (met for’ min hye” droe klor’ ide) Tablets, USP Read the Patient Information that comes with metformin hydrochloride tablets before you start taking them 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 tablets ? Serious side effects can happen in people taking metformin hydrochloride tablets , including: Lactic Acidosis. Metformin hydrochloride, the medicine in metformin hydrochloride 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 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 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. have a genetically inherited disease affecting mitochondria (the energy-producing parts within cells).
What are metformin hydrochloride tablets ? Metformin hydrochloride tablets are prescription medicines that contain metformin hydrochloride. Metformin hydrochloride tablets are used with diet and exercise to help control high blood sugar (hyperglycemia) in adults with type 2 diabetes.
Metformin hydrochloride tablets are not for people with type 1 diabetes. Metformin hydrochloride tablets are not for people with diabetic ketoacidosis (increased ketones in your blood or urine). Metformin hydrochloride tablets help 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 tablets do not cause your body to make more insulin. Who should not take metformin hydrochloride tablets ?
Some conditions increase your chance of getting lactic acidosis, or cause other problems if you take this medicine. Most of the conditions listed below can increase your chance of getting lactic acidosis. Do not take metformin hydrochloride tablets if you: have kidney problems are allergic to the metformin hydrochloride in metformin hydrochloride tablets or any of the ingredients in metformin hydrochloride tablets.
See the end of this leaflet for a complete list of ingredients in metformin hydrochloride tablets. are going to get an injection of dye or contrast agents for an x-ray procedure or if you are going to have surgery and not able to eat or drink much. In these situations, metformin hydrochloride tablets will need to be stopped for a short time. Talk to your healthcare provider about when you should stop metformin hydrochloride tablets and when you should start metformin hydrochlorid… [Excerpted — this section continues on DailyMed.]
📄 Package Label / Principal Display Panel ▾
PRINCIPAL DISPLAY PANEL - 500 mg - Container Label (90's count) NDC 42385-947-90 Metformin Hydrochloride Tablets, USP 500 mg 90 Tablets Rx Only Laurus Labs metformin-hcl-fig1.jpg
PRINCIPAL DISPLAY PANEL - 500 mg - Blister Carton - 100 (10 x 10) Unit-Dose Tablets Laurus Labs NDC 42385-947-19 Metformin Hydrochloride Tablets, USP 500 mg 100 (10 x 10) Unit-Dose Tablets Rx only metformin-hcl-fig2.jpg
PRINCIPAL DISPLAY PANEL - 500 mg - Blister (1 x 10's count) Rx only NDC 42385-947-10 Metformin Hydrochloride Tablet, USP 500 mg Mfd.by: Laurus Labs Limited M.L.No.: 16/VSP/AP/2015/F&B/CC metformin-hcl-fig3.jpg
PRINCIPAL DISPLAY PANEL - 850 mg - Container Label (90's count) NDC 42385-948-90 Metformin Hydrochloride Tablets, USP 850 mg 90 Tablets Rx Only Laurus Labs metformin-hcl-fig4.jpg
PRINCIPAL DISPLAY PANEL - 850 mg - Blister Carton - 100 (10 x 10) Unit-Dose Tablets Laurus Labs NDC 42385-948-19 Metformin Hydrochloride Tablets, USP 850 mg 100 (10 x 10) Unit-Dose Tablets Rx only metformin-hcl-fig5.jpg
PRINCIPAL DISPLAY PANEL - 850 mg - Blister (1 x 10's count) Rx only NDC 42385-948-10 Metformin Hydrochloride Tablet, USP 850 mg M.L.No.: 16/VSP/AP/2015/F&B/CC Mfd.by: Laurus Labs Limited metformin-hcl-fig6.jpg
PRINCIPAL DISPLAY PANEL - 1,000 mg - Container Label (60's count) NDC 42385-949-60 Metformin Hydrochloride Tablets, USP 1,000 mg 60 Tablets Rx Only Laurus Labs metformin-hcl-fig7.jpg
PRINCIPAL DISPLAY PANEL - 1,000 mg - Blister Carton - 100 (10 x 10) Unit-Dose Tablets Laurus Labs NDC 42385-949-19 Metformin Hydrochloride Tablets, USP 1,000 mg 100 (10 x 10) Unit-Dose Tablets Rx only metformin-hcl-fig8.jpg
PRINCIPAL DISPLAY PANEL - 1,000 mg - Blister (1 x 10's count) Rx only NDC 42385-949-10 Metformin Hydrochloride Tablet, USP 1,000 mg M.L.No.: 16/VSP/AP/2015/F&B/CC Mfd.by: Laurus Labs Limited metformin-hcl-fig9.jpg