GLUMETZA- metformin hydrochloride tablet, film coated, extended release

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

METFORMIN HYDROCHLORIDE (UNII: 786Z46389E) (METFORMIN - UNII:9100L32L2N)

Available from:

Santarus, Inc.

INN (International Name):

METFORMIN HYDROCHLORIDE

Composition:

METFORMIN HYDROCHLORIDE 500 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

GLUMETZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. GLUMETZA is contraindicated in patients with: - Severe renal impairment (eGFR below 30 mL/minute/1.73 m2) [see Warnings and Precautions ( 5.1)] . - Known hypersensitivity to metformin. - Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Risk Summary Limited data with GLUMETZA in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk [see Data]. There are risks to the mother and fetus associated with poorly controlled diabetes mellitus in pregnancy [see Clinical Considerations]. No adverse developmental effects were observed when metformin was administered to pregnant Sprague Dawley rats and rabbits during the period of organogenesis at doses up to 3 and 1 times, respectively, a 2,000 mg clinical dose, based on body surface area [see Data]. The estimated background risk of major birth defects is 6–10% in women with pregestational diabetes mellitus with an HbA1c >7 and has been reported to be as high as 20–25% in women with an HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, 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 postmarketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy. However, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Animal Data Metformin HCl was not teratogenic or embyrolethal when administered to rats prior to pregnancy through the period of organogenesis at doses up to 900 mg/kg, or when administered to rabbits during the period of organogenesis at doses up to 90 mg/kg. 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 GLUMETZA and any potential adverse effects on the breastfed child from GLUMETZA 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. Discuss the potential for unintended pregnancy with premenopausal women as therapy with GLUMETZA may result in ovulation in some anovulatory women. Safety and effectiveness of GLUMETZA in pediatric patients have not been established. Clinical studies of GLUMETZA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis. Assess renal function more frequently in elderly patients [see Dosage and Administration ( 2.2) and Warnings and Precautions ( 5.1)]. Metformin is substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of renal impairment. GLUMETZA is contraindicated in severe renal impairment, patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m2 [see Dosage and Administration ( 2.2), Contraindications ( 4), Warnings and Precautions ( 5.1), and Clinical Pharmacology ( 12.3)]. Use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis. GLUMETZA is not recommended in patients with hepatic impairment [see Warnings and Precautions ( 5.1)].

Product summary:

GLUMETZA is supplied as: 500 mg Bottles of 100 NDC 68012-004-50 white, film-coated, oval-shaped, extended-release tablets with “M500” on one side. 1,000 mg Bottles of 90 NDC 68012-003-16 white, film-coated, oval-shaped, extended-release tablets with “M1000” on one side. 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].

Authorization status:

New Drug Application

Summary of Product characteristics

GLUMETZA- METFORMIN HYDROCHLORIDE TABLET, FILM COATED, EXTENDED
RELEASE
SANTARUS, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
GLUMETZA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR GLUMETZA.
GLUMETZA
(METFORMIN HYDROCHLORIDE) EXTENDED-RELEASE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1995
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 GLUMETZA AND INSTITUTE
GENERAL
SUPPORTIVE MEASURES IN A HOSPITAL SETTING. PROMPT HEMODIALYSIS IS
RECOMMENDED. (
5.1)
INDICATIONS AND USAGE
GLUMETZA is a biguanide indicated as an adjunct to diet and exercise
to improve glycemic control in
adults with type 2 diabetes mellitus. ( 1)
DOSAGE AND ADMINISTRATION
Starting dose: 500 mg orally once daily with the evening meal ( 2.1)
Increase the dose in increments of 500 mg every 1 to 2 weeks, up to a
maximum of 2,000 mg once
daily with the evening meal. ( 2.1)
Patients receiving metformin hydrochloride (HCl) tablets may be
switched to GLUMETZA once daily at
the same total daily dose, up to 2,000 mg once daily. ( 2.1)
Swallow GLUMETZA tablets whole and never crush, cut or chew. ( 2.1)
Re