Glucophage XR 500mg Tablets (24 Hr)
WARNING: Rarely, metformin may cause too much lactic acid in the blood (lactic acidosis). The risk is higher in people who have kidney problems, liver problems, heart failure, use alcohol, or take certain other drugs, including topiramate. The risk is also higher in people who are 65 or older and in people who are having surgery, an exam or test with contrast, or other procedures. If lactic acidosis happens, it can lead to other health problems and can be deadly. Kidney tests may be done while taking this drug.Do not take this drug if you have a very bad infection, low oxygen, or a lot of fluid loss (dehydration).Call your doctor right away if you have signs of too much lactic acid in the blood (lactic acidosis) like confusion; fast breathing; fast or slow heartbeat; a heartbeat that does not feel normal; very bad stomach pain, upset stomach, or throwing up; feeling very sleepy; shortness of breath; feeling very tired or weak; very bad dizziness; feeling cold; or muscle pain or cramps. @ COMMON USES: It is used to lower blood sugar in patients with high blood sugar (diabetes).
Drug Class
Antidiabetic
Pharmacologic Class
Biguanide
Pregnancy Category
Not available (old Category B)
FDA Approved
Oct 2000
DEA Schedule
Not Controlled
Overview
What is this medicine?
Glucophage XR is an extended-release tablet containing metformin, a medicine used to treat type 2 diabetes. It helps your body use insulin more effectively, lowers the amount of sugar your liver makes, and reduces the sugar your body absorbs from food. This helps to lower your blood sugar levels.
How to Use This Medicine
Taking Your Medication
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely. Take your medication with meals to help your body absorb it properly. Even if you start to feel well, continue taking your medication as directed by your doctor or healthcare provider.
If you are taking your medication once daily, take it with your evening meal. Swallow the tablet whole - do not chew, break, or crush it. If you have difficulty swallowing, consult with your doctor for guidance.
Storing and Disposing of Your Medication
To maintain the effectiveness and safety of your medication, store it at room temperature, protected from light. Keep it in a dry place, away from the bathroom. Ensure that all medications are kept in a secure location, out of the reach of children and pets.
What to Do If You Miss a Dose
If you miss a dose, skip it and resume your normal dosing schedule unless your doctor advises you to do otherwise. Do not take two doses at the same time or take extra doses to make up for the missed one.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely. Take your medication with meals to help your body absorb it properly. Even if you start to feel well, continue taking your medication as directed by your doctor or healthcare provider.
If you are taking your medication once daily, take it with your evening meal. Swallow the tablet whole - do not chew, break, or crush it. If you have difficulty swallowing, consult with your doctor for guidance.
Storing and Disposing of Your Medication
To maintain the effectiveness and safety of your medication, store it at room temperature, protected from light. Keep it in a dry place, away from the bathroom. Ensure that all medications are kept in a secure location, out of the reach of children and pets.
What to Do If You Miss a Dose
If you miss a dose, skip it and resume your normal dosing schedule unless your doctor advises you to do otherwise. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take Glucophage XR with your evening meal to help reduce stomach upset and improve absorption.
- Swallow the tablet whole; do not crush, chew, or break it, as this will affect its extended-release properties.
- Follow a healthy diet plan recommended by your doctor or dietitian.
- Engage in regular physical activity as advised by your healthcare provider.
- Monitor your blood sugar levels regularly as instructed.
- Limit alcohol intake, as it can increase the risk of a serious side effect called lactic acidosis.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 500 mg orally once daily with the evening meal. Titrate: Increase by 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved, consider 1000 mg twice daily.
Dose Range:
500 - 2500 mg
Condition-Specific Dosing:
Type 2 Diabetes Mellitus:
Initial: 500 mg once daily with evening meal. Max: 2000 mg once daily or 1000 mg twice daily. Some sources cite max 2500 mg/day for XR, but 2000 mg is more common for once daily dosing.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established (Glucophage XR is not recommended for use in pediatric patients younger than 10 years of age. Metformin IR is approved for children 10 years and older.)
Adolescent:
Not established (Glucophage XR is not recommended for use in pediatric patients younger than 10 years of age. Metformin IR is approved for children 10 years and older.)
Dose Adjustments
Renal Impairment:
Mild:
eGFR 60-89 mL/min/1.73m²: No dose adjustment needed. Monitor eGFR annually.
Moderate:
eGFR 45-59 mL/min/1.73m²: Assess benefits/risks of continuing. If already on metformin, reduce dose by 50% or discontinue. If initiating, not recommended. Monitor eGFR every 3-6 months. eGFR 30-44 mL/min/1.73m²: Not recommended to initiate. If already on metformin, discontinue.
Severe:
eGFR <30 mL/min/1.73m²: Contraindicated.
Dialysis:
Contraindicated in patients with end-stage renal disease (ESRD) or on dialysis due to accumulation and increased risk of lactic acidosis.
Hepatic Impairment:
Mild:
Not available (Use with caution)
Moderate:
Not available (Use with caution)
Severe:
Contraindicated due to increased risk of lactic acidosis.
Pharmacology
Mechanism of Action
Metformin is a biguanide that improves glycemic control by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. It does not stimulate insulin secretion and therefore does not cause hypoglycemia when used as monotherapy.
Pharmacokinetics
Absorption:
Bioavailability:
50-60% (for IR, XR is designed for slower absorption)
Tmax:
4-8 hours (for XR)
FoodEffect:
Food increases the extent of absorption (AUC) and prolongs Tmax for Glucophage XR. It should be taken with the evening meal.
Distribution:
Vd:
654 ± 358 L
ProteinBinding:
Negligible (<5%)
CnssPenetration:
Limited
Elimination:
HalfLife:
Plasma elimination half-life is approximately 6.2 hours; blood half-life is approximately 17.6 hours (due to distribution into red blood cells).
Clearance:
Renal clearance is approximately 3.5 times greater than creatinine clearance, indicating tubular secretion.
ExcretionRoute:
Renal (urine)
Unchanged:
>90%
Pharmacodynamics
OnsetOfAction:
Within days
PeakEffect:
1-2 weeks (to achieve full therapeutic effect)
DurationOfAction:
Approximately 24 hours (for XR formulation)
Safety & Warnings
BLACK BOX WARNING
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 distress. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate/pyruvate ratio; metformin plasma levels were generally >5 mcg/mL. 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 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. If metformin-associated lactic acidosis is suspected, discontinue Glucophage XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following signs or symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Stomach problems that occur later during treatment, which may be a sign of lactic acidosis (an acid health problem in the blood)
Low blood sugar, which may be more likely when this medication is used with other diabetes medications. Signs of low blood sugar include:
+ Dizziness
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
If you experience low blood sugar, follow your doctor's instructions for treatment, which may include taking glucose tablets, liquid glucose, or some fruit juices.
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to contact your doctor or seek medical help if you notice any of the following:
Stomach pain or heartburn
Gas
Diarrhea
Upset stomach or vomiting
Feeling tired or weak
* Headache
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following signs or symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Stomach problems that occur later during treatment, which may be a sign of lactic acidosis (an acid health problem in the blood)
Low blood sugar, which may be more likely when this medication is used with other diabetes medications. Signs of low blood sugar include:
+ Dizziness
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
If you experience low blood sugar, follow your doctor's instructions for treatment, which may include taking glucose tablets, liquid glucose, or some fruit juices.
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to contact your doctor or seek medical help if you notice any of the following:
Stomach pain or heartburn
Gas
Diarrhea
Upset stomach or vomiting
Feeling tired or weak
* Headache
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Symptoms of lactic acidosis (a rare but serious side effect): unusual muscle pain, unusual tiredness, trouble breathing, stomach pain, dizziness, lightheadedness, feeling cold, or a slow or irregular heartbeat. Seek immediate medical attention if these occur.
- Symptoms of low blood sugar (hypoglycemia): sweating, shaking, fast heartbeat, hunger, confusion, dizziness. This is rare with metformin alone but can occur if used with other diabetes medications or if you skip meals.
- Symptoms of vitamin B12 deficiency (with long-term use): unusual tiredness, weakness, numbness or tingling in hands or feet.
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction you experienced, including the symptoms that occurred.
Certain health conditions, including:
+ Acidic blood problems
+ Kidney disease
+ Liver disease
Recent medical events, such as a heart attack or stroke
Any difficulties with eating or drinking, including situations where you may be required to fast before a procedure or surgery
* Upcoming or recent exams or tests that involve contrast agents, particularly if they have taken place within the past 48 hours. Discuss these procedures with your doctor to ensure safe management.
This list is not exhaustive, and it is crucial to disclose all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues to your doctor and pharmacist. This will help determine if it is safe to take this medication in conjunction with your other treatments and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor to ensure your safety.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction you experienced, including the symptoms that occurred.
Certain health conditions, including:
+ Acidic blood problems
+ Kidney disease
+ Liver disease
Recent medical events, such as a heart attack or stroke
Any difficulties with eating or drinking, including situations where you may be required to fast before a procedure or surgery
* Upcoming or recent exams or tests that involve contrast agents, particularly if they have taken place within the past 48 hours. Discuss these procedures with your doctor to ensure safe management.
This list is not exhaustive, and it is crucial to disclose all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues to your doctor and pharmacist. This will help determine if it is safe to take this medication in conjunction with your other treatments and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor to ensure your safety.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Before consuming alcohol, discuss the potential risks with your doctor.
If you experience low blood sugar, do not operate a vehicle, as this can increase your risk of being involved in an accident. Monitor your blood sugar levels as instructed by your doctor, and undergo blood tests as recommended by your healthcare provider. Discuss any concerns or questions with your doctor.
During periods of stress, such as fever, infection, injury, or surgery, it may be more challenging to manage your blood sugar levels. Changes in physical activity, exercise, or diet can also impact your blood sugar control. Adhere to the diet and exercise plan prescribed by your doctor to maintain optimal blood sugar management.
If you experience diarrhea or vomiting, contact your doctor promptly, as you may need to increase your fluid intake to prevent excessive fluid loss. Be cautious in hot weather or during intense physical activity, and drink plenty of fluids to avoid dehydration.
Long-term treatment with metformin may lead to a decrease in vitamin B-12 levels. If you have a history of low vitamin B-12 levels, consult with your doctor. You may notice the appearance of the tablet in your stool, but this is a normal occurrence and not a cause for concern. If you have any questions, discuss them with your doctor.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects. Women of childbearing age who have not been ovulating may be at risk of pregnancy while taking this medication. To avoid pregnancy, use birth control measures while taking this drug.
If you are pregnant, plan to become pregnant, or are breastfeeding, inform your doctor. It is crucial to discuss the potential benefits and risks of this medication to both you and your baby.
If you experience low blood sugar, do not operate a vehicle, as this can increase your risk of being involved in an accident. Monitor your blood sugar levels as instructed by your doctor, and undergo blood tests as recommended by your healthcare provider. Discuss any concerns or questions with your doctor.
During periods of stress, such as fever, infection, injury, or surgery, it may be more challenging to manage your blood sugar levels. Changes in physical activity, exercise, or diet can also impact your blood sugar control. Adhere to the diet and exercise plan prescribed by your doctor to maintain optimal blood sugar management.
If you experience diarrhea or vomiting, contact your doctor promptly, as you may need to increase your fluid intake to prevent excessive fluid loss. Be cautious in hot weather or during intense physical activity, and drink plenty of fluids to avoid dehydration.
Long-term treatment with metformin may lead to a decrease in vitamin B-12 levels. If you have a history of low vitamin B-12 levels, consult with your doctor. You may notice the appearance of the tablet in your stool, but this is a normal occurrence and not a cause for concern. If you have any questions, discuss them with your doctor.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects. Women of childbearing age who have not been ovulating may be at risk of pregnancy while taking this medication. To avoid pregnancy, use birth control measures while taking this drug.
If you are pregnant, plan to become pregnant, or are breastfeeding, inform your doctor. It is crucial to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Lactic acidosis (most serious and common symptom of overdose)
- Hypoglycemia (less common with metformin alone)
- Severe gastrointestinal upset (nausea, vomiting, diarrhea, abdominal pain)
What to Do:
Immediately contact emergency services or a poison control center (Call 1-800-222-1222). Treatment involves supportive measures and prompt hemodialysis to remove metformin and correct acidosis.
Drug Interactions
Contraindicated Interactions
- Iodinated contrast media (temporarily discontinue metformin at the time of or prior to the procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m2; 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 if renal function is stable.)
- Alcohol (acute or chronic alcohol intake can potentiate metformin's effect on lactate metabolism, increasing lactic acidosis risk)
Major Interactions
- Carbonic anhydrase inhibitors (e.g., topiramate, zonisamide, acetazolamide, dichlorphenamide): May increase risk of lactic acidosis.
- Drugs that reduce metformin clearance (e.g., cimetidine, ranolazine, dolutegravir, isavuconazonium, trimethoprim, vandetanib): May increase metformin plasma concentrations and risk of lactic acidosis.
- Diuretics (especially loop diuretics): May increase risk of lactic acidosis due to potential for renal impairment.
- Corticosteroids, sympathomimetics, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, calcium channel blockers, isoniazid: May cause hyperglycemia, requiring dose adjustment of metformin.
Moderate Interactions
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Renal function (eGFR)
Rationale: Metformin is primarily eliminated by the kidneys; impaired renal function increases risk of accumulation and lactic acidosis.
Timing: Prior to initiation
HbA1c
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation
Vitamin B12 levels
Rationale: Metformin can decrease vitamin B12 absorption, especially with long-term use or higher doses.
Timing: Consider prior to initiation, especially in patients with risk factors for B12 deficiency.
Routine Monitoring
Renal function (eGFR)
Frequency: At least annually; more frequently (e.g., every 3-6 months) in patients at risk for renal impairment (e.g., elderly, those with comorbidities).
Target: >60 mL/min/1.73m² (adjust or discontinue if <45 mL/min/1.73m²)
Action Threshold: Discontinue if eGFR falls below 30 mL/min/1.73m². Re-evaluate if eGFR is 30-44 mL/min/1.73m².
HbA1c
Frequency: Every 3-6 months
Target: Individualized, typically <7% for most non-pregnant adults.
Action Threshold: If target not met, consider dose adjustment or addition of other antidiabetic agents.
Vitamin B12 levels
Frequency: Periodically (e.g., every 1-2 years) or if symptoms of B12 deficiency (e.g., anemia, neuropathy) develop.
Target: Normal range (e.g., 200-900 pg/mL)
Action Threshold: Supplement B12 if levels are low or symptoms are present.
Symptom Monitoring
- Symptoms of lactic acidosis: malaise, myalgia, somnolence, respiratory distress, abdominal distress, unusual fatigue, dizziness, lightheadedness, bradycardia, hypothermia. Seek immediate medical attention.
- Symptoms of hypoglycemia (rare as monotherapy): sweating, tremor, hunger, confusion, dizziness (more likely if used with insulin or sulfonylureas).
- Gastrointestinal side effects: nausea, vomiting, diarrhea, abdominal discomfort (common, especially at initiation).
Special Patient Groups
Pregnancy
Metformin is often continued or initiated in pregnancy for gestational diabetes or type 2 diabetes, especially if diet and exercise are insufficient. While older classification was Category B, current practice focuses on risk/benefit. Studies suggest it may be a reasonable option, but insulin remains a primary treatment.
Trimester-Specific Risks:
First Trimester:
Limited data, but generally considered low risk. Some studies suggest potential for lower gestational weight gain and reduced risk of large for gestational age infants.
Second Trimester:
Generally considered safe and effective for glycemic control.
Third Trimester:
Generally considered safe and effective for glycemic control.
Lactation
Metformin is excreted into breast milk in small amounts. The amount ingested by the infant is generally considered too low to cause adverse effects. It is generally considered compatible with breastfeeding (L2).
Infant Risk:
Low risk. Monitor breastfed infants for signs of hypoglycemia or gastrointestinal upset, though these are rare.
Pediatric Use
Glucophage XR is not recommended for use in pediatric patients younger than 10 years of age. Metformin immediate-release (IR) is approved for children 10 years and older for type 2 diabetes.
Geriatric Use
Use with caution in elderly patients due to increased likelihood of decreased renal function. Renal function should be assessed more frequently in older patients. The risk of lactic acidosis increases with age and declining renal function.
Clinical Information
Clinical Pearls
- Metformin is considered first-line pharmacologic therapy for type 2 diabetes, especially in overweight or obese patients, due to its efficacy, low risk of hypoglycemia (as monotherapy), and potential for weight neutrality or modest weight loss.
- The extended-release formulation (XR) is often preferred for patients experiencing significant gastrointestinal side effects with immediate-release metformin, as it may improve tolerability.
- Patients should be educated on the symptoms of lactic acidosis and the importance of discontinuing the medication and seeking immediate medical attention if these symptoms occur.
- It is crucial to temporarily discontinue metformin before or at the time of iodinated contrast imaging procedures in at-risk patients and restart only after renal function has been re-evaluated and found stable.
- Regular monitoring of renal function is paramount for all patients on metformin, especially the elderly and those with comorbidities affecting kidney function.
- Metformin can cause vitamin B12 deficiency with long-term use; consider periodic monitoring and supplementation if indicated.
Alternative Therapies
- Sulfonylureas (e.g., glipizide, glyburide, glimepiride)
- DPP-4 inhibitors (e.g., sitagliptin, saxagliptin, linagliptin)
- SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, dapagliflozin)
- GLP-1 receptor agonists (e.g., liraglutide, semaglutide, dulaglutide)
- Thiazolidinediones (TZDs) (e.g., pioglitazone, rosiglitazone)
- Insulin
Cost & Coverage
Average Cost:
Varies widely, typically $10-$50 per 30 tablets (for generic)
Generic Available:
Yes
Insurance Coverage:
Tier 1 (Generic) or Tier 2 (Brand)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it is a good idea to consult with your pharmacist. If you have any questions or concerns about this medication, do not hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.