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Riomet Metformin Hydrochloride 500 mg/5mL Solution, 118 mL — NDC 10631-0206-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Riomet Metformin Hydrochloride 500 mg/5mL Solution, 118 mL — NDC 10631-206-01 (Billing 10631-0206-01)

by Sun Pharmaceutical Industries, Inc. · 118 mL in 1 BOTTLE

This is a package of 118 mL of Riomet Metformin Hydrochloride 500 mg/5mL Solution from Sun Pharmaceutical Industries, Inc., marketed since Jan 2004 and currently FDA-listed. It is the main listing for this product, which comes in 2 package sizes.

NDC 10631-0206-01
🏷️ FDA NDC (as labeled) 10631-206-01 billing pads the product segment with a zero
This package
Contains118 mL Pack sizes2 compare ↓
Main listing for product 10631-206 · Also comes in: 473 ml 10631-206-02
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 10631-206-01 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
10631 labeler · 206 product · 01 package
Package marketed since
Jan 4, 2004
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Billing quantity
118 mL per package
Barcode (UPC-A, from the NDC)
3 1063120601 7
FDA record last changed
Jul 24, 2026
⚠️
Other active recalls for Metformin Hydrochloride (different manufacturers) — 2 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Mar 13, 2025 — CGMP Deviations (Glenmark Pharmaceuticals Inc., USA) · FDA recall D-0328-2025
Class II · Feb 25, 2025 — Presence of Foreign Tablets/Capsules. (A-S Medication Solutions LLC) · FDA recall D-0292-2025
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 10631-206-01
Product NDC 10631-206
11-digit billing NDC 10631020601
NCPDP billing unit ML — per mL (volume)
RxCUI 861025, 861027
UNII 786Z46389E
Application # NDA021591
SPL Set ID 05d4df4b-dfe8-4828-b423-a3d4f2c4114a
Established class (EPC) Biguanide
Chemical class Biguanides
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2004-01-04
Route ORAL
Dosage form SOLUTION
Substance METFORMIN HYDROCHLORIDE

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 27250050002020
GPI class Riomet
GCN Seq No 053351
GCN 20808
HICL code 004763
Ingredient (HICL) Metformin Hcl
HIC1 code C
Therapeutic class — broad (HIC1) Electrolyte Balance/Metabolism/Nutrition
HIC2 code C4
Therapeutic class — intermediate (HIC2) Antihyperglycemics
HIC3 code C4L
Therapeutic class — specific (HIC3) Antihyperglycemic, Biguanide Type
AHFS code 68:20.04.00
AHFS class Biguanides
FDB label name RIOMET 500 MG/5 ML SOLUTION
FDB brand name Riomet
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 053351
  • GCN: 20808
  • GPI-14 (Medi-Span): 27250050002020
  • HICL (First Databank): 004763
  • AHFS class code: 68:20.04.00
  • RxCUI (RxNorm): 861025
Why two NDCs? The FDA registers this code as 10631-206-01 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 10631-0206-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Biguanide class.

Pharmacologic class Biguanide
Drug family (ATC) Biguanides
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name RIOMET 500 MG/5 ML SOLUTION Ingredient Metformin Hcl
📖 What it is MedlinePlus · NLM

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 ↗
📗 Our plain-language guide HelloPharmacist
  • 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?
📖 Read our full Metformin guide →
4
Nutrient depletion considerations

Metformin Hydrochloride may be associated with lower levels of 4 nutrients — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Metformin Hydrochloride nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Try another pack size: 473 ml
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
10631-0206-01 You're viewing this Main listing 118 mL in 1 BOTTLE 2004-01-04 — Active
10631-0206-02 10631-206-02 473 mL in 1 BOTTLE 2004-01-04 — Active

You're viewing the smallest of 2 pack sizes for this product.

Pack size FAQ

What quantity is in this package?
This package contains 118 mL — 118 ml in 1 bottle.
How does this package differ from NDC 10631-0206-02?
Both are Riomet Metformin Hydrochloride 500 mg/5mL Solution — the drug itself is identical. This page's package is the 118 mL one, while NDC 10631-0206-02 is the 473 ml package.
What NDC number is used to bill for this package of Riomet Metformin Hydrochloride 500 mg/5mL Solution?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Metformin Hydrochloride 500 mg/5mL 31722-0042-47 Camber 1 bottle $0.383 AB Availability likely —
Metformin Hydrochloride Oral Solution 500 mg/5mL 42571-0360-07 MICRO 473 ml $0.383 AB Availability likely —
Metformin Hydrochloride 500 mg/5mL 66689-0318-16 VistaPharm, 1 bottle $0.383 AB Availability likely —
Riomet 500 mg/5mLthis 10631-0206-01 Sun 118 ml — — FDA listed —
Riomet 500 mg/5mL 10631-0238-01 Sun 118 ml — — FDA listed —
Metformin Hydrochloride Oral Solution 500 mg/5mL 52817-0820-50 TRUPHARMA, 10 cups — AB FDA listed —
Metformin Hydrochloride Oral Solution 500 mg/5mL 52817-0821-50 TRUPHARMA, 10 cups — AB FDA listed —
Metformin Hydrochloride Oral Solution 500 mg/5mL 69452-0380-55 Bionpharma 118 ml — AB FDA listed —
Metformin Hydrochloride Oral Solution 500 mg/5mL 71656-0017-04 Saptalis 118 ml — AB FDA listed —
About this product: this is the brand-name version. FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2004
On the market since
Jan 2004
📍
2026
Currently FDA-listed
22 years listed
🔓
·
Generic versions listed
see equivalents
✅Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

What it looks like

FlavorCherry
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

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.

  • UNII QTT17582CB
    A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
  • UNII HM5Z15LEBN
    Potassium bicarbonate is a salt that acts as a buffer and pH regulator in medicines. It helps maintain a stable acid-alkaline balance so the drug stays effective and doesn't irritate the stomach or mouth.
  • UNII SB8ZUX40TY
    Saccharin sodium is an artificial sweetener made from saccharin salt. It's added to medicines to improve taste, especially in liquid formulations for children or bitter drugs.
  • UNII VCQ006KQ1E
    Xylitol is a naturally occurring sugar alcohol derived from plants. It's used in medicines as a sweetener, bulking agent, and to improve taste, especially in liquid formulations and chewable tablets.

4 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerSun Pharmaceutical Industries, Inc.
Application holderRANBAXY SIGNATURE LLC
FDA applicationNDA021591 (NDA)
Labeler code10631
First marketedJan 2004
Product typeHuman Prescription Drug
Portfolio890 products on file

More NDCs from Sun Pharmaceutical Industries, Inc. labeler code 10631

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Patient Medication Information 🧬 Pharmacokinetics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~1 min read ▾

WARNING: LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin ‑ associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin ‑ associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL [see Warnings and Precautions (5.1) ].

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided [see Dosage and Administration (2.3), Contraindications (4), Warnings and Precautions (5.1) ].

If metformin-associated lactic acidosis is suspected, immediately discontinue RIOMET and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see Warnings and Precautions (5.1) ]. WARNING: LACTIC ACIDOSIS See full prescribing information for complete boxed warning • Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias.

Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally > 5 mcg/mL. (5.1) • Risk factors include renal impairment, concomitant use of certain drugs, age ≥ 65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment.

Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the Full Prescribing Information. (5.1) • If lactic acidosis is suspected, discontinue RIOMET and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

(5.1)

🎯 Indications and Usage 67 words ▾

1 INDICATIONS AND USAGE RIOMET is 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. RIOMET is 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 ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Adult Dosage for RIOMET : • Starting dose: 500 mg (5 mL) orally twice a day or 850 mg (8.5 mL) once a day, with meals (2.1) • Increase the dose in increments of 500 mg (5 mL) weekly or 850 mg (8.5 mL) every 2 weeks, up to a maximum dose of 2,550 mg (25.5 mL) per day, given in divided doses (2.1) • Doses above 2,000 mg (20 mL) may be better tolerated given in divided doses 3 times a day with meals (2.1) Pediatric Dosage for RIOMET : • Starting dose: 500 mg (5 mL) orally twice a day, with meals (2.2) • Increase dosage in increments of 500 mg (5 mL) weekly up to a maximum of 2,000 mg (20 mL) 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 RIOMET 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: • RIOMET may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures (2.4)

2.1Adult Dosage • Measure the RIOMET dose in the RIOMET specific dosing cup. • The recommended starting dose of RIOMET is 500 mg (5 mL) orally twice a day or 850 mg (8.5 mL) once a day, given with meals. • Increase the dose in increments of 500 mg (5 mL) weekly or 850 mg (8.5 mL) every 2 weeks on the basis of glycemic control and tolerability, up to a maximum dose of 2,550 mg (25.5 mL) per day, given in divided doses. • Doses above 2,000 mg (20 mL) may be better tolerated given in divided doses 3 times a day with meals.

2.2Pediatric Dosage • Measure the RIOMET dose in the RIOMET specific dosing cup. • The recommended starting dose of RIOMET for pediatric patients 10 years of age and older is 500 mg (5 mL) orally twice a day, given with meals. • Increase dosage in increments of 500 mg (5 mL) weekly on the basis of glycemic control and tolerability, up to a maximum of 2,000 mg (20 mL) per day, given in divided doses twice daily.

2.3Recommendations for Use in Renal Impairment • Assess renal function prior to initiation of RIOMET and periodically thereafter. • RIOMET is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m 2 . • Initiation of RIOMET in patients with an eGFR between 30 to 45 mL/minute/1.73 m 2 is not recommended. • In patients taking RIOMET whose eGFR later falls below 45 mL/min/1.73 m 2 , assess the benefit risk of continuing therapy. • Discontinue RIOMET 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 RIOMET 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 RIOMET if renal function is stable.

💊 Dosage Forms and Strengths 36 words ▾

3 DOSAGE FORMS AND STRENGTHS Oral solution: 500 mg per 5 mL (100 mg/mL) clear solution in cherry and strawberry flavor Oral Solution: 500 mg per 5 mL (100 mg/mL) in cherry and strawberry flavor (3)

⛔ Contraindications 75 words ▾

4 CONTRAINDICATIONS 1. RIOMET is contraindicated in patients with: 2. Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) [see Warnings and Precautions (5.1) ].

3. Hypersensitivity to metformin. 4.

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 ~3 min read ▾

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 RIOMET. In RIOMET 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 RIOMET 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: • Before initiating RIOMET, obtain an estimated glomerular filtration rate (eGFR). • RIOMET is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 [see Contraindications (4) ]. • Initiation of RIOMET is not recommended in patients with eGFR between 30 to 45 mL/min/1.73 m 2 . • Obtain an eGFR at least annually in all patients taking RIOMET.

In patients at risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently. • In patients taking RIOMET whose eGFR falls below 45 mL/min/1.73 m 2 , assess the benefit and risk of continuing therapy. • 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 (2.3), Clinical Pharmacology (12.3) ]: • Before initiating RIOMET, obtain an estimated glomerular filtration rate (eGFR). • RIOMET is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 [see Contraindications (4) ]. • Initiation of RIOMET is not recommended in patients with eGFR between 30 to 45 mL/min/1.73 m 2 . • Obtain an eGFR at least annually in all patients taking RIOMET. In patients at risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently. • In patients taking RIOMET 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 RIOMET… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

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)] The most common adverse reactions are diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch

6.1Clinical Studies Experience 1. 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. 2.

In a U.S. clinical trial of metformin HCl tablets in patients with type 2 diabetes mellitus, a total of 141 patients received metformin HCl tablets up to 2,550 mg per day. Adverse reactions reported in greater than 5% of patients treated with metformin HCl tablets and that were more common than in placebo-treated patients, are listed in Table 1. 3.

Table 1: Adverse Reactions from a Clinical Trial of Metformin HCl Tablets Occurring >5% and More Common than Placebo in Patients with Type 2 Diabetes Mellitus 1. Metformin HCl Tablets (n = 141) 1. Placebo (n = 145) 1.

Diarrhea 1. 53% 1. 12% 1.

Nausea/Vomiting 1. 26% 1. 8% 1.

Flatulence 1. 12% 1. 6% 1.

Asthenia 1. 9% 1. 6% 1.

Indigestion 1. 7% 1. 4% 1.

Abdominal Discomfort 1. 6% 1. 5% 1.

Headache 1. 6% 1. 5% 1.

Diarrhea led to discontinuation of metformin HCl tablets in 6% of patients. Additionally, the following adverse reactions were reported in ≥ 1% to ≤ 5% of patients treated with metformin HCl tablets and were more commonly reported than placebo: abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation. 2.

Pediatric Patients 3. In clinical trials with metformin HCl tablets in pediatric patients with type 2 diabetes mellitus, the profile of adverse reactions was similar to that observed in adults. 4.

Laboratory Tests 5. Vitamin B 12 Concentrations 6. In clinical trials of 29-week duration with metformin HCl tablets, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of patients.

6.2Postmarketing Experience • The following adverse reactions have been identified during post approval use of metformin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. • Cholestatic, hepatocellular, and mixed hepatocellular liver injury have been reported with postmarketing use of metformin.

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS 1. Table 2 presents clinically significant drug interactions with RIOMET. 2.

Table 2: Clinically Significant Drug Interactions with RIOMET 1. Carbonic Anhydrase Inhibitors 1. Clinical Impact: 1.

Carbonic anhydrase inhibitors frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with RIOMET may increase the risk for lactic acidosis. 1.

Intervention: 1. Consider more frequent monitoring of these patients. 1.

Examples: 1. Topiramate, zonisamide, acetazolamide or dichlorphenamide. 1.

Drugs that Reduce RIOMET Clearance 1. Clinical Impact: 1. 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 [OCT 2 ] / 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)].

1. Intervention: 1. Consider the benefits and risks of concomitant use with RIOMET.

1. Examples: 1. Ranolazine, vandetanib, dolutegravir, and cimetidine.

1. Alcohol 1. Clinical Impact: 1.

Alcohol is known to potentiate the effect of metformin on lactate metabolism. 1. Intervention: 1.

Warn patients against excessive alcohol intake while receiving RIOMET. 1. Insulin Secretagogues or Insulin 1.

Clinical Impact: 1. Coadministration of RIOMET with an insulin secretagogue (e.g., sulfonylurea) or insulin may increase the risk of hypoglycemia. 1.

Intervention: 1. Patients receiving an insulin secretagogue or insulin may require lower doses of the insulin secretagogue or insulin. 1.

Drugs Affecting Glycemic Control 1. Clinical Impact: 1. Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control.

1. Intervention: 1. When such drugs are administered to a patient receiving RIOMET, observe the patient closely for loss of blood glucose control.

When such drugs are withdrawn from a patient receiving RIOMET, observe the patient closely for hypoglycemia. 1. Examples: 1.

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 ~3 min read ▾

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 1. Risk Summary 2. Limited data with RIOMET 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]. 3.

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]. 4. 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. 5.

Clinical Considerations 6. Disease-associated maternal and/or embryo/fetal risk 7. 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. 8. Data 9.

Human Data 10. 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.

11. Animal Data 12. 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 RIOMET and any potential adverse effects on the breastfed child from RIOMET 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 RIOMET may result in ovulation in some anovulatory women.

8.4Pediatric Use 1. The safety and effectiveness… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy 1. Risk Summary 2. Limited data with RIOMET 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]. 3.

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]. 4. 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. 5.

Clinical Considerations 6. Disease-associated maternal and/or embryo/fetal risk 7. 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. 8. Data 9.

Human Data 10. 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.

11. Animal Data 12. 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 153 words ▾

8.4Pediatric Use 1. The safety and effectiveness of RIOMET for the treatment of type 2 diabetes mellitus have been established in pediatric patients 10 to 16 years old. Safety and effectiveness of RIOMET have not been established in pediatric patients less than 10 years old.

2. Use of RIOMET 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 HCl tablets in adults with additional data from a controlled clinical study of metformin HCl tablets 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)] . In this study, adverse reactions were similar to those described in adults.

A maximum daily dose of 2,000 mg of RIOMET is recommended. [See Dosage and Administration (2.2) .]

🧓 Geriatric Use 89 words ▾

8.5Geriatric Use 1. Controlled clinical studies of metformin HCl tablets did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis.

Assess renal function more frequently in elderly patients [see Warnings and Precautions (5.1) ].

🆘 Overdosage 85 words ▾

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 ~3 min read ▾

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 1. Two pharmacokinetic studies performed in healthy volunteers to evaluate the bioavailability of RIOMET in comparison with metformin HCl tablets under fasting and fed conditions showed that the rate and extent of absorption of RIOMET was found to be comparable to that of metformin HCl tablets under fasting or fed conditions (see Table 3). Table 3: Select Mean (± S.D.) Pharmacokinetic Parameters Following Single Oral Doses of 1000 mg RIOMET and Metformin HCl tablets in healthy, nondiabetic adults (n = 36) under fed and fasting conditions Formulation C max (ng/mL) AUC 0-∞ (ng.h/mL) T max (h) Study 1- Fasting state RIOMET 1540.1 ± 451.1 9069.6 ± 2593.6 2.2 ±

0.5Metformin HCl Tablets 1885.1 ± 498.5 11100.1 ± 2733.1 2.5 ±

0.6T/R Ratio X 100 (90% confidence interval) 81.2 (76.3 to 86.4) 81.2 (76.9 to 85.6) - Study 2- Fed State RIOMET 1235.3 ± 177.7 8950.1 ± 1381.2 4.1 ±

0.8Metformin HCl Tablets 1361 ± 298.8 9307.7 ± 1839.8 3.7 ±

0.8T/R Ratio X 100 (90% confidence interval) 91.8 (87.4 to 96.5) 97.0 (92.9 to 101.2) - 1. T-test product (RIOMET) 2. R-reference product (immediate release metformin HCl tablets) 3.

Studies using single oral doses of metformin HCl tablets 500 mg to 1,500 mg, and 850 mg 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, steady state plasma concentrations of metformin are reached within 24 to 48 hours and are generally < 1 mcg/mL. 4.

Effect of food: The food-effect study assessed the effects of a high fat/high calorie meal and a low fat/low calorie meal on the bioavailability of RIOMET in comparison with administration in the fasted state, in healthy volunteers. The extent of absorption was increased by approximately 16% and 13% with the low fat/low calorie meal and the high fat/high calorie meal, respectively, compared with the administration in the fasted state. The rate and extent of absorption with high fat/high calorie and low fat/ low calorie meal were similar.

The mean t max was 2.5 hours under fasting conditions as compared to 3.9 hours with both low fat/ low calorie meal and high fat/high calorie meals (see Table 4). Table 4: Select Mean (± S.D.) Metformin Pharmacokinetic Parameters Following Single Oral Doses of 1,000 mg RIOMET in healthy, nondiabetic adults (n = 33) under fed (high fat/high calorie meal and low fat/low calorie meal) and fasting conditions (study 3) Meal type C max (ng/mL) AUC 0-∞ (ng.h/mL) t max (h) Fasting (F) 1641.5 ± 551.8 9982.9 ± 2544.5 2.5 ±

0.9Low fat/ low calorie meal (L) 1525.8 ± 396.7 11542.0 ± 2947.5 3.9 ±

0.6High fat/high calorie meal (H) 1432.5 ± 346.8 11184.5 ± 2446.1 3.9 ±

0.8L/F Ratio X 100 (90% confidence interval) 94.6 (84.0 to 106.5) 115.6 (103.6 to 128.9) - H/F Ratio X 100 (90% confidence interval) 89.4 (79.4 to 100.6) 112.6 (100.9 to 125.6) - L/H Ratio X 100 (90% confidence interval) 105.8 (94.0 to 119.2) 102.7 (92.0 to 114.6) - 1. Distribution 2. The apparent volume of distribution (V/F) of metformin following single oral doses of metformin HCl 850 mg averaged 654 ± 358 L.

Metformin is negligibly bound to plasma proteins. Metformin partitions into erythrocytes, most likely as a function of time. 3.

Metabolism 4. Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine a… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 67 words ▾

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 87 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied 1. RIOMET 500 mg per 5 mL (100 mg/mL) oral solution is supplied in bottles with child-resistant caps and a dosing cup as follows: Flavor Appearance Size NDC Cherry clear, colorless solution 4 ounce (118 mL) 10631-206-01 16 ounce (473 mL) 10631-206-02 Strawberry clear, colorless to light yellow solution 4 ounce (118 mL) 10631-238-01 16 ounce (473 mL) 10631-238-02 Storage 1. Store at 15 ° - 30 ° C (59 ° - 86 ° F) [See USP Controlled Room Temperature].

📋 Description 183 words ▾

11 DESCRIPTION RIOMET oral solution contains the biguanidine antihyperglycemic agent metformin in the form of monohydrochloride salt. Metformin hydrochloride, is N , N -dimethylimidodicarbonimidic diamide hydrochloride. The structural formula is shown as: Metformin hydrochloride, USP is a white crystalline powder with a molecular formula of C 4 H 11 N 5 •HCl and a molecular weight of 165.62.

Metformin hydrochloride, USP 2.0 g is soluble in 20 mL of water. The pK a of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68.

It is freely soluble in water; slightly soluble in alcohol; practically insoluble in acetone and in methylene chloride. RIOMET (Cherry Flavor) contains 500 mg of metformin hydrochloride (the equivalent of 389.93 mg metformin) per 5 mL and the following inactive ingredients: Artificial cherry flavor, hydrochloric acid, potassium bicarbonate, purified water, saccharin calcium, and xylitol. RIOMET (Strawberry Flavor) contains 500 mg of metformin hydrochloride (the equivalent of 389.93 mg metformin) per 5 mL and the following inactive ingredients: Hydrochloric acid, N&A strawberry flavor (propylene glycol and glycerin), potassium bicarbonate, purified water, sucralose, and xylitol. structure

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION 1. Advise the patient to read the FDA-approved patient labeling (Patient Information). 2.

Administration: 3. Instruct patients or caregivers to use the supplied dosing cup to measure the prescribed amount of medication. Inform patients that additional RIOMET dosing cups or oral dosing syringes may be obtained from their pharmacy.

4. Lactic Acidosis: 5. Explain the risks of lactic acidosis, its symptoms, and conditions that predispose to its development.

Advise patients to discontinue RIOMET 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 RIOMET. Instruct patients to inform their doctor that they are taking RIOMET prior to any surgical or radiological procedure, as temporary discontinuation may be required [see Warnings and Precautions (5.1)].

6. Hypoglycemia 7. Inform patients that hypoglycemia may occur when RIOMET is 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)]. 8. Vitamin B12 Deficiency: 9.

Inform patients about importance of regular hematological parameters while receiving RIOMET [see Warnings and Precautions (5.2)] . 10. Females of Reproductive Age: 11.

Inform females that treatment with RIOMET may result in ovulation in some premenopausal anovulatory women which may lead to unintended pregnancy [see Use in Specific Populations (8.3)]. 12. RIOMET is a registered trademark of Sun Pharmaceutical Industries Limited.

13. Manufactured by: 14. Mikart, LLC 15.

Atlanta, GA 30318 16. Distributed by: 17. Sun Pharmaceutical Industries, Inc.

18. Cranbury, NJ 08512 19. November 2018 FDA-11

💬 Patient Medication Information ~3 min read ▾

Patient Medication Information • PATIENT INFORMATION • RIOMET (ree oh met) • (metformin hydrochloride) • oral solution • What is the most important information I should know about RIOMET? • RIOMET can cause serious side effects, including: • Lactic Acidosis . Metformin hydrochloride, the medicine in RIOMET, 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 RIOMET 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 sleepiness or sleep longer than usual • have unusual (not normal) muscle pain • feel cold, especially in your arms and legs • have trouble breathing • feel dizzy or lightheaded • have unexplained stomach or intestinal problems with nausea and vomiting, or diarrhea • have a slow or irregular heartbeat 1.

You have a higher chance of getting lactic acidosis if you: 2. have moderate to severe kidney problems. See “ Do not take RIOMET if you ” 3. have liver problems. 4. have congestive heart failure that requires treatment with medicines.

5. drink a lot of alcohol (very often or short-term “binge” drinking). 6. 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. 7. have certain x-ray tests with injectable dyes or contrast agents. 8. have surgery.

9. have a heart attack, severe infection, or stroke. 10. are 65 years of age or older. 11.

Tell your healthcare provider if you have any of the problems in the list above. 12. Tell your healthcare provider that you are taking RIOMET before you have surgery or x-ray tests.

Your healthcare provider may need to stop RIOMET for a while if you have surgery or certain x-ray tests. 13. RIOMET can have other serious side effects.

See “ What are the possible side effects of RIOMET?” 14. What is RIOMET? 15.

RIOMET is a prescription medicine that contains metformin hydrochloride. RIOMET is used with diet and exercise to help control high blood sugar (hyperglycemia) in adults and children 10 years of age and older with type 2 diabetes. 16.

It is not known if RIOMET is safe and effective in children under 10 years of age. 17. Do not take RIOMET if you: 18. have severe kidney problems.

19. are allergic to the metformin hydrochloride or any of the ingredients in RIOMET. See the end of this Patient Information leaflet for a complete list of ingredients in RIOMET. 20. have a condition called metabolic acidosis including diabetic ketoacidosis (high levels of certain acids called “ketones” in your blood or urine).

21. Before taking RIOMET tell your healthcare provider about all your medical conditions, including if you: 22. have a history or risk for diabetic ketoacidosis. See “ Do not take RIOMET if you? ” 23. have kidney problems.

24. have liver problems. 25. have heart problems, including congestive heart failure. 26. are 65 years or older.

27. drink alcohol very often or drink a lot of alcohol in short-term “binge” drinking. 28. are taking insulin or a sulfonylurea medicine. 29. are pregnant or plan to become pregnant.

It is not known if RIOMET will harm your unborn baby. If you are pregnant, talk with your healthcare provider about the best way to control your blood sugar while you are pregnant. 30. are a premenopausal woman who does not have periods regularly or at all.

RIOMET can cause the release of an egg from an ovary in a woman (ovulation). This can increase your chance of getting pregnant. 31. are breastfeeding or plan to breastfeed.

RIOMET can pass into your breast milk. Talk with your healthcare provider about the best way to feed your baby while you take RIOMET. 32.

Tell your healthcare provider about all the medicines you take, including prescription a… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics 1. Two pharmacokinetic studies performed in healthy volunteers to evaluate the bioavailability of RIOMET in comparison with metformin HCl tablets under fasting and fed conditions showed that the rate and extent of absorption of RIOMET was found to be comparable to that of metformin HCl tablets under fasting or fed conditions (see Table 3). Table 3: Select Mean (± S.D.) Pharmacokinetic Parameters Following Single Oral Doses of 1000 mg RIOMET and Metformin HCl tablets in healthy, nondiabetic adults (n = 36) under fed and fasting conditions Formulation C max (ng/mL) AUC 0-∞ (ng.h/mL) T max (h) Study 1- Fasting state RIOMET 1540.1 ± 451.1 9069.6 ± 2593.6 2.2 ±

0.5Metformin HCl Tablets 1885.1 ± 498.5 11100.1 ± 2733.1 2.5 ±

0.6T/R Ratio X 100 (90% confidence interval) 81.2 (76.3 to 86.4) 81.2 (76.9 to 85.6) - Study 2- Fed State RIOMET 1235.3 ± 177.7 8950.1 ± 1381.2 4.1 ±

0.8Metformin HCl Tablets 1361 ± 298.8 9307.7 ± 1839.8 3.7 ±

0.8T/R Ratio X 100 (90% confidence interval) 91.8 (87.4 to 96.5) 97.0 (92.9 to 101.2) - 1. T-test product (RIOMET) 2. R-reference product (immediate release metformin HCl tablets) 3.

Studies using single oral doses of metformin HCl tablets 500 mg to 1,500 mg, and 850 mg 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, steady state plasma concentrations of metformin are reached within 24 to 48 hours and are generally < 1 mcg/mL. 4.

Effect of food: The food-effect study assessed the effects of a high fat/high calorie meal and a low fat/low calorie meal on the bioavailability of RIOMET in comparison with administration in the fasted state, in healthy volunteers. The extent of absorption was increased by approximately 16% and 13% with the low fat/low calorie meal and the high fat/high calorie meal, respectively, compared with the administration in the fasted state. The rate and extent of absorption with high fat/high calorie and low fat/ low calorie meal were similar.

The mean t max was 2.5 hours under fasting conditions as compared to 3.9 hours with both low fat/ low calorie meal and high fat/high calorie meals (see Table 4). Table 4: Select Mean (± S.D.) Metformin Pharmacokinetic Parameters Following Single Oral Doses of 1,000 mg RIOMET in healthy, nondiabetic adults (n = 33) under fed (high fat/high calorie meal and low fat/low calorie meal) and fasting conditions (study 3) Meal type C max (ng/mL) AUC 0-∞ (ng.h/mL) t max (h) Fasting (F) 1641.5 ± 551.8 9982.9 ± 2544.5 2.5 ±

0.9Low fat/ low calorie meal (L) 1525.8 ± 396.7 11542.0 ± 2947.5 3.9 ±

0.6High fat/high calorie meal (H) 1432.5 ± 346.8 11184.5 ± 2446.1 3.9 ±

0.8L/F Ratio X 100 (90% confidence interval) 94.6 (84.0 to 106.5) 115.6 (103.6 to 128.9) - H/F Ratio X 100 (90% confidence interval) 89.4 (79.4 to 100.6) 112.6 (100.9 to 125.6) - L/H Ratio X 100 (90% confidence interval) 105.8 (94.0 to 119.2) 102.7 (92.0 to 114.6) - 1. Distribution 2. The apparent volume of distribution (V/F) of metformin following single oral doses of metformin HCl 850 mg averaged 654 ± 358 L.

Metformin is negligibly bound to plasma proteins. Metformin partitions into erythrocytes, most likely as a function of time. 3.

Metabolism 4. 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. 5.

Elimination 6. Renal clearance (see Table 5) 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 appro… [Excerpted — this section continues on DailyMed.]

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES 1. Adult Clinical Studies 2. A double-blind, placebo-controlled, multicenter US clinical trial involving obese patients with type 3.

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 HCl tablets (up to 2,550 mg/day) or placebo for 29 weeks. The results are presented in Table 8.

4. Table 8: Mean Change in Fasting Plasma Glucose and HbA1c at Week 29Comparing Metformin HCl Tablets vs Placebo in Patients with Type 2Diabetes Mellitus 1. Metformin HCL 2.

Tablets (n=141) 1. Placebo 2. (n=145) 1. p-Value 1.

FPG (mg/dL) 2. Baseline 3. Change at FINAL VISIT 1.

241.5 2. –53.0 1. 237.7 2. 6.3 1.

NS* 2. 0.001 1. Hemoglobin A 1c (%) 2.

Baseline 3. Change at FINAL VISIT 1. 8.4 2. –1.4 1.

8.22. 0.4 1. NS * 2.

0.001 1. * Not statistically significant 2. Mean baseline body weight was 201 lbs and 206 lbs in the metformin HCl tablet 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 HCl tablet and placebo arms, respectively.

3. A 29-week, double-blind, placebo-controlled study of metformin HCl tablet 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 HCl tablet 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 HCl 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 HCl 2,500 mg. Patients in the metformin only arm (metformin HCl 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 HCl 2,000 mg/glyburide 20 mg or metformin HCl 2,500 mg/glyburide 20 mg. The results are displayed in Table 9.

4. Table 9: Mean Change in Fasting Plasma Glucose and HbA1c at Week 29Comparing Metformin HCl Tablets/Glyburide (Comb) vs Glyburide (Glyb) vs Metformin HCl Tablets (GLU): in Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Glyburide Comb (n = 213) Glyb (n = 209) GLU (n = 210) p-Values Glyb vs Comb GLU vs Comb GLU vs Glyb 1. Fasting Plasma Glucose (mg/dL) 2.

Baseline 3. Change at FINAL VISIT 1. 250.5 2. –63.5 1.

247.5 2. 13.7 1. 253.9 2. –0.9 NS * 0.001 NS * 0.001 NS * 0.025 1.

Hemoglobin A 1c (%) 2. Baseline 3. Change at FINAL VISIT 1.

8.82. –1.7 1. 8.5 2. 0.2 1.

8.92. –0.4 NS * 0.001 NS * 0.001 0.007 0.001 1. * Not statistically significant 2. Mean baseline body weight was 202 lbs, 203 lbs, and 204 lbs in the metformin HCl tablet/glyburide, glyburide, and metformin HCl tablet 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 HCl tablet/glyburide, glyburide, and metformin HCl tablet arms, respectively.

3. Pediatric Clinical Studies 4. A double-blind, placebo-controlled study was conducted in pediatric patients aged 10 to 16 years with type 2 diabetes mellitus (mean FPG 182.2 mg/dL), where patients were treated with metformin HCl tablets (up to 2,000 mg/day) for up to 16 weeks (mean duration of treatment 11 weeks).

The results are displayed in Table 10. 5. Table 10: Mean Change in Fasting Plasma Glucose at Week 16 Comparing Metformin HCl Tablets vs Placebo in Pediatric Patientsa with Type 2Diabetes Mellitus 1.

Metformin HCl Tablets 1. Placebo 1. p-Value 1. FPG (mg/dL) 2.

Baseline 3. Change at FINAL VISIT 1. (n = 37) 2.

162.4 3. –42.9 1. (n… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 194 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility 1. 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.

2. 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.

3. 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 191 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility 1. 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.

2. 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.

3. 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.

📄 Package Label / Principal Display Panel 74 words ▾

PACKAGE LABEL. PRINCIPAL DISPLAY PANEL NDC 10631-238-02 Riomet ® (metformin hydrochloride oral solution) 500 mg/5 mL Each 5 mL contains: 500 mg of metformin hydrochloride, USP. Strawberry Flavor Rx only 16 fl. oz.473 mL Strawberry Flavor label strawberry

Package/Label Display Panel NDC 10631-206-02 Riomet ® (metformin hydrochloride oral solution) 500 mg/5 mL Each 5 mL contains: 500 mg of metformin hydrochloride, USP. Cherry Flavor Rx only 16 fl. oz.473 mL Cherry Flavor label cherry

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Sun Pharmaceutical Industries, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 473 ml (10631-0206-02). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Sun Pharmaceutical Industries, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 10631-0134-31 · Sun 10631-0238-01 · Sun →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.