Complete SPL Sections#
WARNING: LACTIC ACIDOSIS
BOXED WARNING SECTION
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) , (2.7), Contraindications (4) , Warnings and Precautions (5.1) ]. If metformin-associated lactic acidosis is suspected, immediately discontinue metformin hydrochloride and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see Warnings and Precautions (5.1) ].
1 INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
Metformin hydrochloride tablets, USP are indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus.
2 DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
3 DOSAGE FORMS AND STRENGTHS
DOSAGE FORMS & STRENGTHS SECTION
Metformin Hydrochloride Tablets, USP are available as: Tablets: 500 mg white to off white, round, biconvex, flavored, film coated tablets with 'LL' debossed on one side and plain on the other side. Tablets: 850 mg white to off white, capsule shaped, biconvex, flavored, film coated tablets with 'L06' debossed on one side and plain on the other side. Tablets: 1,000 mg white to off white, oval, biconvex, flavored, film coated tablets, with score line on both sides, with 'L' and '11' debossed on either side of score line on one side.
4 CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
Metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) [see Warnings and Precautions (5.1) ]. Hypersensitivity to metformin. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
5 WARNINGS AND PRECAUTIONS
WARNINGS AND PRECAUTIONS SECTION
6 ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
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) ]
7 DRUG INTERACTIONS
DRUG INTERACTIONS SECTION
Table 3 presents clinically significant drug interactions with metformin hydrochloride. Table 3: Clinically Significant Drug Interactions with Metformin Hydrochloride Carbonic Anhydrase Inhibitors Clinical Impact: Carbonic anhydrase inhibitors frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with metformin hydrochloride may increase the risk for lactic acidosis. Intervention: Consider more frequent monitoring of these patients. Examples: Topiramate, zonisamide, acetazolamide or dichlorphenamide. Drugs that Reduce Metformin Hydrochloride Clearance Clinical Impact: Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology (12.3) ]. Intervention: Consider the benefits and risks of concomitant use with metformin hydrochloride. Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine. Alcohol Clinical Impact: Alcohol is known to potentiate the effect of metformin on lactate metabolism. Intervention: Warn patients against excessive alcohol intake while receiving metformin hydrochloride. Insulin Secretagogues or Insulin Clinical Impact: Coadministration of metformin hydrochloride with an insulin secretagogue (e.g., sulfonylurea) or insulin may increase the risk of hypoglycemia. Intervention: Patients receiving an insulin secretagogue or insulin may require lower doses of the insulin secretagogue or insulin. Drugs Affecting Glycemic Control Clinical Impact: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. Intervention: When such drugs are administered to a patient receiving metformin hydrochloride, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin hydrochloride, observe the patient closely for hypoglycemia. Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid.
8 USE IN SPECIFIC POPULATIONS
USE IN SPECIFIC POPULATIONS SECTION
10 OVERDOSAGE
OVERDOSAGE SECTION
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.
11 DESCRIPTION
DESCRIPTION SECTION
Metformin hydrochloride tablets, USP contain the antihyperglycemic agent metformin, which is a biguanide, in the form of monohydrochloride. The chemical name of metformin hydrochloride is N,N -dimethylimidodicarbonimidic diamide hydrochloride. The structural formula is as shown below: Metformin hydrochloride, USP is a white to off-white crystalline compound with a molecular formula of C 4 H 11 N 5 • HCl and a molecular weight of 165.63. It is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pK a of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. Metformin hydrochloride tablets, USP contain 500 mg, 850 mg, or 1,000 mg of metformin hydrochloride, which is equivalent to 389.93 mg, 662.88 mg, 779.86 mg metformin base, respectively. Each tablet contains the inactive ingredients colloidal silicon dioxide, croscarmellose sodium, magnesium stearate and povidone. In addition, the tablet coating material of 500 mg, 850 mg and 1,000 mg tablets contains hypromellose, polyethylene glycol, titanium dioxide and artificial blackberry flavor.
12 CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
13 NONCLINICAL TOXICOLOGY
NONCLINICAL TOXICOLOGY SECTION
14 CLINICAL STUDIES
CLINICAL STUDIES SECTION
16 HOW SUPPLIED/STORAGE AND HANDLING
HOW SUPPLIED SECTION
Metformin Hydrochloride Tablets USP, 850 mg are supplied as white to off white, capsule shaped, biconvex, flavored, film coated tablets with ‘L06’ debossed on one side and plain on the other side. NDC 71335-2593-1: 60 Tablets in a BOTTLE NDC 71335-2593-2: 30 Tablets in a BOTTLE NDC 71335-2593-3: 120 Tablets in a BOTTLE NDC 71335-2593-4: 90 Tablets in a BOTTLE NDC 71335-2593-5: 100 Tablets in a BOTTLE NDC 71335-2593-6: 180 Tablets in a BOTTLE Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Dispense in light-resistant containers. Repackaged/Relabeled by: Bryant Ranch Prepack Burbank, CA 91504
17 PATIENT COUNSELING INFORMATION
INFORMATION FOR PATIENTS SECTION
Advise the patient to read the FDA-approved patient labeling (Patient Information). Lactic Acidosis: Explain the risks of lactic acidosis, its symptoms, and conditions that predispose to its development. Advise patients to discontinue metformin hydrochloride tablets immediately and to promptly notify their healthcare provider if unexplained hyperventilation, myalgias, malaise, unusual somnolence or other nonspecific symptoms occur. Counsel patients against excessive alcohol intake and inform patients about importance of regular testing of renal function while receiving metformin hydrochloride tablets. Instruct patients to inform their doctor that they are taking metformin hydrochloride tablets prior to any surgical or radiological procedure, as temporary discontinuation may be required [see Warnings and Precautions (5.1) ]. Hypoglycemia Inform patients that hypoglycemia may occur when metformin hydrochloride tablets are coadministered with oral sulfonylureas and insulin. Explain to patients receiving concomitant therapy the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development [see Warnings and Precautions (5.3)] . Vitamin B 12 Deficiency: Inform patients about importance of regular hematological parameters while receiving metformin hydrochloride tablets [see Warnings and Precautions (5.2) ] . F emales of Reproductive Age: Inform females that treatment with metformin hydrochloride tablets may result in ovulation in some premenopausal anovulatory women which may lead to unintended pregnancy [see Use in Specific Populations (8.3) ]. Dispense with Patient Information available at: h ttps://www.laurusgenerics.us/met-patient-info.pdf Manufactured for: Laurus Generics Inc. 400 Connell Drive Suite 5200 Berkeley Heights, NJ 07922 Manufactured by: Laurus Labs Limited Anakapalli-531011 India Revised: 08/2023
PATIENT INFORMATION
SPL PATIENT PACKAGE INSERT SECTION
Metformin Hydrochloride (met for' min hye" droe klor' ide) Tablets, USP Read the Patient Information that comes with metformin hydrochloride tablets before you start taking them and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or treatment. What is the most important information I should know about metformin hydrochloride tablets ? Serious side effects can happen in people taking metformin hydrochloride tablets , including: Lactic Acidosis. Metformin hydrochloride, the medicine in metformin hydrochloride tablets, can cause a rare, but serious, side effect called lactic acidosis (a build-up of lactic acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in a hospital. Stop taking metformin hydrochloride tablets and call your healthcare provider right away if you get any of the following symptoms of lactic acidosis: feel very weak and tired have unusual (not normal) muscle pain have trouble breathing have unusual sleepiness or sleep longer than usual have unexplained stomach or intestinal problems with nausea and vomiting, or diarrhea feel cold, especially in your arms and legs feel dizzy or lightheaded have a slow or irregular heartbeat You have a higher chance of getting lactic acidosis if you: have kidney problems. People whose kidneys are not working properly should not take metformin hydrochloride tablets. have liver problems. have congestive heart failure that requires treatment with medicines. drink a lot of alcohol (very often or short-term “binge” drinking). get dehydrated (lose a large amount of body fluids). This can happen if you are sick with a fever, vomiting, or diarrhea. Dehydration can also happen when you sweat a lot with activity or exercise and do not drink enough fluids. have certain x-ray tests with injectable dyes or contrast agents. have surgery. have a heart attack, severe infection, or stroke. are 80 years of age or older and have not had your kidney function tested. What are metformin hydrochloride tablets ? Metformin hydrochloride tablets are prescription medicines that contain metformin hydrochloride. Metformin hydrochloride tablets are used with diet and exercise to help control high blood sugar (hyperglycemia) in adults with type 2 diabetes. Metformin hydrochloride tablets are not for people with type 1 diabetes. Metformin hydrochloride tablets are not for people with diabetic ketoacidosis (increased ketones in your blood or urine). Metformin hydrochloride tablets help control your blood sugar in a number of ways. These include helping your body respond better to the insulin it makes naturally, decreasing the amount of sugar your liver makes, and decreasing the amount of sugar your intestines absorb. Metformin hydrochloride tablets do not cause your body to make more insulin. Who should not take metformin hydrochloride tablets ? Some conditions increase your chance of getting lactic acidosis, or cause other problems if you take this medicine. Most of the conditions listed below can increase your chance of getting lactic acidosis. Do not take metformin hydrochloride tablets if you: have kidney problems are allergic to the metformin hydrochloride in metformin hydrochloride tablets or any of the ingredients in metformin hydrochloride tablets. See the end of this leaflet for a complete list of ingredients in metformin hydrochloride tablets. are going to get an injection of dye or contrast agents for an x-ray procedure or if you are going to have surgery and not able to eat or drink much. In these situations, metformin hydrochloride tablets will need to be stopped for a short time. Talk to your healthcare provider about when you should stop metformin hydrochloride tablets and when you should start metformin hydrochloride tablets again. See “ What is the most important information I should know about metformin hydrochloride tablets? ” What should I tell my healthcare provider before taking metformin hydrochloride tablets ? Before taking metformin hydrochloride tablets, tell your healthcare provider if you: have type 1 diabetes. Metformin hydrochloride tablets should not be used to treat people with type 1 diabetes. have a history or risk for diabetic ketoacidosis (high levels of certain acids, known as ketones, in the blood or urine). Metformin hydrochloride tablets should not be used for the treatment of diabetic ketoacidosis. have kidney problems. have liver problems. have heart problems, including congestive heart failure. are older than 80 years. If you are over 80 years old you should not take metformin hydrochloride tablets unless your kidneys have been checked and they are normal. drink alcohol very often, or drink a lot of alcohol in short-term “binge” drinking. are taking insulin. have any other medical conditions. are pregnant or plan to become pregnant. It is not known if metformin hydrochloride tablets 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. are breast-feeding or plan to breast-feed. It is not known if metformin hydrochloride passes into your breast milk. Talk with your healthcare provider about the best way to feed your baby while you take metformin hydrochloride tablets. Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. Metformin hydrochloride tablets may affect the way other medicines work, and other medicines may affect how metformin hydrochloride tablets work. Can metformin hydrochloride tablets be used in children? Metformin hydrochloride tablets have been shown to effectively lower glucose levels in children (ages 10 to 16 years) with type 2 diabetes. Metformin hydrochloride tablets have not been studied in children younger than 10 years old. Metformin hydrochloride tablets have not been studied in combination with other oral glucose-control medicines or insulin in children. If you have any questions about the use of metformin hydrochloride tablets in children, talk with your doctor or other healthcare provider. How should I take metformin hydrochloride tablets ? Take metformin hydrochloride tablets exactly as your healthcare provider tells you. Metformin hydrochloride tablets should be taken with meals to help lessen an upset stomach side effect. Swallow metformin hydrochloride tablets whole. You may sometimes pass a soft mass in your stools (bowel movement) that looks like metformin hydrochloride tablets. When your body is under some types of stress, such as fever, trauma (such as a car accident), infection, or surgery, the amount of diabetes medicine that you need may change. Tell your healthcare provider right away if you have any of these problems. Your healthcare provider should do blood tests to check how well your kidneys are working before and during your treatment with metformin hydrochloride tablets. Your healthcare provider will check your diabetes with regular blood tests, including your blood sugar levels and your hemoglobin A1C. Follow your healthcare provider’s instructions for treating blood sugar that is too low (hypoglycemia). Talk to your healthcare provider if low blood sugar is a problem for you. See “ What are the possible side effects of metformin hydrochloride tablets ? ” Check your blood sugar as your healthcare provider tells you to. Stay on your prescribed diet and exercise program while taking metformin hydrochloride tablets. If you miss a dose of metformin hydrochloride tablets, take your next dose as prescribed unless your healthcare provider tells you differently. Do not take an extra dose the next day. If you take too much metformin hydrochloride tablets, call your healthc...
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
metFORMIN HCL 850mg Tab
