Boxed Warning (Black Box)
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 c...
METFORMIN HYDROCHLORIDE
METFORMIN HYDROCHLORIDE
Manufacturer: A-S Medication Solutions
Clinical information
Indications & Usage
1 INDICATIONS & USAGE Metformin hydrochloride tablets 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. Metformin hydrochloride extended-release tablets is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Metformin 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) Metformin is a biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. (1)
Dosage & Administration
2 DOSAGE & ADMINISTRATION Adult Dosage for Metformin Hydrochloride Tablets: Starting dose: 500 mg orally twice a day or 850 mg once a day, with meals (2.1) 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) Adult Dosage for Metformin Hydrochloride Extented-Release Tablets: Swallow metformin hydrochloride extended-release tablets whole and never crush, cut or chew (2.1) Starting dose: 500 mg orally once daily with the evening meal (2.1) Increase the dose in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal (2.1) Patients receiving metformin hydrochloride tablets may be switched to metformin hydrochloride extended-release tablets once daily at the same total daily dose, up to 2000 mg once daily (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) Asses 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 and metformin hydrochloride extended-release tablets may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures (2.4) 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. Metformin Hydrochloride Extended-Release Tablets Swallow metformin hydrochloride extended-release tablets whole and never crush, cut or chew. The recommended starting dose of metformin hydrochloride extended-release tablets is 500 mg orally once daily with the evening meal. Increase the dose in increments of 500 mg weekly on the basis of glycemic control and tolerability, up to a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved with metformin hydrochloride extended-release tablets 2000 mg once daily, consider a trial of metformin hydrochloride extended-release tablets 1000 mg twice daily. If higher doses are required, switch to metformin hydrochloride tablets at total daily doses up to 2550 mg administered in divided daily doses, as described above. Patients receiving metformin hydrochloride tablets may be switched to metformin hydrochloride extended-release tablets once daily at the same total daily dose, up to 2000 mg once daily. 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 metformin hydrochloride extended-release tablets and periodically thereafter. Metformin hydrochloride tablets and metformin hydrochloride extended-release 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 and metformin hydrochloride extended-release tablets in patients with an eGFR between 30 – 45 mL/minute/1.73 m 2 is not recommended. In patients taking metformin hydrochloride tablets and metformin hydrochloride extended-release tablets whose eGFR later falls below 45 mL/min/1.73 m 2 , assess the benefit risk of continuing therapy. Discontinue metformin hydrochloride tablets and metformin hydrochloride extended-release 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 and metformin hydrochloride extended-release 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 and metformin hydrochloride extended-release tablets if renal function is stable.
Contraindications
4 CONTRAINDICATIONS Metformin hydrochloride tablets and metformin hydrochloride extended-release tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m2) [see Warnings and Precautions ( 5.1 ) ]. Hypersensitivity to metformin. 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)
Safety
Adverse Reactions
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 )] For metformin hydrochloride tablets and metformin hydrochloride extended-release tablets, the most common adverse reactions (>5.0%) are diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASCRX01 (877-272-7901) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience 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. Metformin Hydrochloride Tablets In a U.S. clinical trial of metformin hydrochloride tablets in patients with type 2 diabetes mellitus, a total of 141 patients received metformin hydrochloride tablets up to 2,550 mg per day. Adverse reactions reported in greater than 5% of metformin hydrochloride tablets treated patients and that were more common than in placebo-treated patients, are listed in Table 1. Table 1: Adverse Reactions from a Clinical Trial of Metformin Hydrochloride Tablets Occurring >5% and More Common than Placebo in Patients with Type 2 Diabetes Mellitus Metformin Hydrochloride Tablets (n=141) Placebo (n=145) Diarrhea 53% 12% Nausea/Vomiting 26% 8% Flatulence 12% 6% Asthenia 9% 6% Indigestion 7% 4% Abdominal Discomfort 6% 5% Headache 6% 5% Diarrhea led to discontinuation of metformin hydrochloride tablets in 6% of patients. Additionally, the following adverse reactions were reported in ≥1% to ≤5% of metformin hydrochloride tablets treated patients and were more commonly reported with metformin hydrochloride tablets than placebo: abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation. In metformin hydrochloride tablets clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of patients. Pediatric Patients In clinical trials with metformin hydrochloride tablets in pediatric patients with type 2 diabetes mellitus, the profile of adverse reactions was similar to that observed in adults. Metformin Hydrochloride Extended-Release Tablets In placebo-controlled trials, 781 patients were administered metformin hydrochloride extended-release tablets. Adverse reactions reported in greater than 5% of the metformin hydrochloride extended-release tablets patients, and that were more common in metformin hydrochloride extended-release tablets- than placebo-treated patients, are listed in Table 2. Table 2: Adverse Reactions from Clinical Trials of Metformin Hydrochloride Extended-Release Tablets Occurring >5% and More Common than Placebo in Patients with Type 2 Diabetes Mellitus Metformin Hydrochloride Extended-Release Tablets Placebo (n=781) (n=195) Diarrhea 10% 3% Nausea/Vomiting 7% 2% Diarrhea led to discontinuation of metformin hydrochloride extended-release tablets in 0.6% of patients. Additionally, the following adverse reactions were reported in ≥1.0% to ≤5.0% of metformin hydrochloride extended-release tablets patients and were more commonly reported with metformin hydrochloride extended-release tablets than placebo: abdominal pain, constipation, distention abdomen, dyspepsia/heartburn, flatulence, dizziness, headache, upper respiratory infection, taste disturbance. 6.2 Postmarketing 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
7 DRUG INTERACTIONS Table 3 presents clinically significant drug interactions with metformin hydrochloride tablets and metformin hydrochloride extended-release tablets. Table 3: Clinically Significant Drug Interactions with Metformin Hydrochloride Tablets And Metformin Hydrochloride Extended-Release Tablets 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 tablets and metformin hydrochloride extended-release tablets 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 Tablets and Metformin Hydrochloride Extended-Release Tablets 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 tablets and metformin hydrochloride extended-release tablets. 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 receivingmetformin hydrochloride tablets and metformin hydrochloride extended-release tablets. Insulin Secretagogues or Insulin Clinical Impact: Coadministration of metformin hydrochloride tablets and metformin hydrochloride extended-release tabletswith 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 tablets and metformin hydrochloride extended-release tablets, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin hydrochloride tablets and metformin hydrochloride extended-release tablets, 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. 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)
Additional information
Description
11 DESCRIPTION Metformin hydrochloride tablets and metformin hydrochloride extended-release tablets 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. Metformin hydrochloride 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 hydrochloride is 6.68. Metformin hydrochloride tablets USP contain 500 mg, 850 mg, or 1000 mg of metformin hydrochloride USP. Each tablet contains the inactive ingredients corn starch, povidone and magnesium stearate. In addition, the coating for each tablet contains hypromellose, talc, titanium dioxide, polyethylene glycol, and propylene glycol. Metformin hydrochloride extended-release tablets, USP contains 500 mg or 750 mg of metformin hydrochloride as the active ingredient. Metformin hydrochloride extended-release tablets USP, 500 mg and 750 mg contain the inactive ingredients sodium carboxymethyl cellulose, hypromellose, microcrystalline cellulose, magnesium stearate and copovidone. FDA approved dissolution test specifications differ from USP. Structure
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-5246 NDC: 50090-5246-0 90 TABLET, EXTENDED RELEASE in a BOTTLE NDC: 50090-5246-1 60 TABLET, EXTENDED RELEASE in a BOTTLE NDC: 50090-5246-2 100 TABLET, EXTENDED RELEASE in a BOTTLE NDC: 50090-5246-3 30 TABLET, EXTENDED RELEASE in a BOTTLE
Related medications
Frequently Asked Questions
What is metformin hydrochloride used for?+
Metformin hydrochloride is used to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes. It is used in conjunction with diet and exercise to help manage blood sugar levels. Consult a doctor to determine if metformin hydrochloride is right for your specific condition.
Can I take metformin hydrochloride if I have kidney problems?+
Metformin hydrochloride is not recommended for patients with severe kidney problems, as it can increase the risk of lactic acidosis. If you have kidney problems, your doctor may need to adjust your dose or monitor your kidney function while taking metformin hydrochloride. Consult a doctor to discuss your individual situation and determine the best course of treatment.
How long does it take for metformin hydrochloride to start working?+
Metformin hydrochloride can start to lower blood sugar levels within a few days to a week after starting treatment. However, it may take several weeks to see the full effects of the medication. Consult a doctor to monitor your progress and adjust your treatment plan as needed.
Can I take metformin hydrochloride if I am pregnant or breastfeeding?+
Metformin hydrochloride is generally considered safe to use during pregnancy, but it is essential to discuss the potential risks and benefits with your doctor. If you are breastfeeding, metformin hydrochloride may pass into your milk, so it is crucial to consult a doctor before taking the medication. Consult a doctor to determine the best course of treatment for your individual situation.
What are the common side effects of metformin hydrochloride?+
Common side effects of metformin hydrochloride include nausea, vomiting, diarrhea, and stomach upset. In some cases, metformin hydrochloride can also cause more severe side effects, such as lactic acidosis. Consult a doctor if you experience any side effects, as they can help you manage them and determine the best course of treatment.
MEDICAL DISCLAIMER
MedLeaflet provides information sourced directly from the FDA openFDA API. This is NOT professional medical advice and should not replace consultation with a licensed healthcare provider. Do not use this site to self-diagnose or self-medicate. Always consult your doctor or pharmacist before starting, stopping, or changing any medication.