DOSAGE & ADMINISTRATION SECTION

Highlight: Adult Dosage for metformin hydrochloride tablets:

• Starting dose: 500 mg orally twice a day or 850 mg once a day, with meals
• Increase the dose in increments of 500 mg weekly or 850 mg every 2 weeks, up to a maximum dose of 2550 mg per day, given in divided doses ( 2.1)
• Doses above 2000 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 2000 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 30-45 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 DOSAGE AND ADMINISTRATION

2.1 Adult 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 2550 mg per day, given in divided doses.
• Doses above 2000 mg may be better tolerated given 3 times a day with meals.

2.2 Pediatric 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 2000 mg per day, given in divided doses twice daily.

2.3 Recommendations for Use in Renal Impairment

Assess renal function prior to initiation of metformin hydrochloride tablets and periodically thereafter.

Metformin hydrochloride tablets is 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 – 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)]

2.4 Discontinuation 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.

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NONCLINICAL TOXICOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, 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 1500 mg/kg/day, respectively. These doses are both approximately 3 times the maximum recommended human daily dose of 2550 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 2550 mg based on body surface area comparisons.

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INFORMATION FOR PATIENTS SECTION

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 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)].

Vitamin B 12 Deficiency:
Inform patients about importance of regular hematological parameters while receiving metformin hydrochloride tablets [see Warnings and Precautions (5.2)].

Females 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 by:

Chartwell Pharmaceuticals, LLC.

Congers, NY 10920

Distributed by:

LifSa Drugs, LLC

New Brunswick, NJ 08901

L70884

Rev: 04/2022

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HOW SUPPLIED SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Table 12: Metformin Hydrochloride Tablets Available Strengths, Units, and Appearance

16.2 Storage

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature]
Dispense in tight, light-resistant containers with child-resistant closure.

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