Metformin

Metformin
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Deepika Beereddy, MBBS [2]

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Black Box Warning

Title See full prescribing information for complete Boxed Warning. ConditionName: Content

Overview

Metformin is a hypoglycemic agent that is FDA approved for the treatment of type 2 diabetes mellitus. There is a Black Box Warning for this drug as shown here. Common adverse reactions include cobalamin deficiency, diarrhea, flatulence, indigestion, malabsorption syndrome, nausea, vomiting, asthenia, headache.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Type 2 diabetes mellitus

• Dosing Information

• Dosage

Off-Label Use and Dosage (Adult)

Non–Guideline-Supported Use

Hyperinsulinar obesity

• Dosing Information

• Dosage

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Metformin FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Contraindications

Metformin Hydrochloride (HCl) Tablets, USP is an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin HCl, USP (N,N-dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents.

The structural formula is as shown:

17bd7b7d-figure-01 Metformin HCl, USP is a white to off-white crystalline compound with a molecular formula of C4H11N5 • HCl and a molecular weight of 165.62. Metformin HCl, USP is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin HCl, USP is 6.68.

Metformin HCl Tablets, USP, contains 500 mg, 850 mg, or 1000 mg of metformin HCl, USP. Each tablet contains the inactive ingredients povidone, microcrystalline cellulose, croscarmellose sodium and magnesium stearate. In addition, the coating for the 500 mg, 850 mg and 1000 mg tablets contain polyethylene glycol, polyvinyl alcohol, titanium dioxide, talc, gum acacia, maltodextrin, propylene glycol and natural flavors.

Warnings

Title See full prescribing information for complete Boxed Warning. ConditionName: Content

• Description

Precautions

• Description

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Metformin in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Metformin in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Metformin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Metformin during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Metformin with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Metformin with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Metformin with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Metformin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Metformin with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Metformin in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Metformin in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Metformin in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Metformin in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

• Intravenous

Monitoring

There is limited information regarding Monitoring of Metformin in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Metformin in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Metformin in the drug label.

Pharmacology

There is limited information regarding Metformin Pharmacology in the drug label.

Mechanism of Action

Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects (except in special circumstances, see PRECAUTIONS) and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.

Structure

File:Metformin01.png

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Metformin in the drug label.

Pharmacokinetics

Absorption and Bioavailability

The absolute bioavailability of a Metformin HCl 500 mg tablet given under fasting conditions is approximately 50% to 60%. Studies using single oral doses of Metformin HCl 500 mg to 1500 mg, and 850 mg to 2550 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. Food decreases the extent of and slightly delays the absorption of metformin, as shown by approximately a 40% lower mean peak plasma concentration (Cmax), a 25% lower area under the plasma concentration versus time curve (AUC), and a 35 minute prolongation of time to peak plasma concentration (Tmax) following administration of a single 850 mg tablet of metformin with food, compared to the same tablet strength administered fasting. The clinical relevance of these decreases is unknown.

Distribution

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, in contrast to sulfonylureas, which are more than 90% protein bound. Metformin partitions into erythrocytes, most likely as a function of time. At usual clinical doses and dosing schedules of Metformin HCl, steady-state plasma concentrations of metformin are reached within 24 to 48 hours and are generally <1 mcg/mL. During controlled clinical trials of Metformin HCl, maximum metformin plasma levels did not exceed 5 mcg/mL, even at maximum doses.

Metabolism and Elimination

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. Renal clearance (see Table 1) is approximately 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.

Special Populations

Patients with Type 2 Diabetes

In the presence of normal renal function, there are no differences between single- or multiple-dose pharmacokinetics of metformin between patients with type 2 diabetes and normal subjects (see Table 1), nor is there any accumulation of metformin in either group at usual clinical doses.

Renal Insufficiency

In patients with decreased renal function (based on measured creatinine clearance), the plasma and blood half-life of metformin is prolonged and the renal clearance is decreased in proportion to the decrease in creatinine clearance (see Table 1; also see WARNINGS).

Hepatic Insufficiency

No pharmacokinetic studies of metformin have been conducted in patients with hepatic insufficiency.

Geriatrics

Limited data from controlled pharmacokinetic studies of Metformin HCl in healthy elderly subjects suggest that total plasma clearance of metformin is decreased, the half-life is prolonged, and Cmax is increased, compared to healthy young subjects. From these data, it appears that the change in metformin pharmacokinetics with aging is primarily accounted for by a change in renal function (see Table 1). Metformin HCl Tablets treatment should not be initiated in patients ≥80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced (see WARNINGS and DOSAGE AND ADMINISTRATION).

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Metformin in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Metformin in the drug label.

How Supplied

Storage

There is limited information regarding Metformin Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Metformin in the drug label.

Precautions with Alcohol

• Alcohol-Metformin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Fortamet, Glucophage, Glucophage XR, Riomet, Glumetza.

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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