Glucophage XR 750mg 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 Agent
Pharmacologic Class
Biguanide
Pregnancy Category
Category B
FDA Approved
May 2000
DEA Schedule
Not Controlled
Overview
What is this medicine?
Glucophage XR 750mg is an extended-release tablet containing metformin. It's used to help control high blood sugar levels in people with type 2 diabetes. It works by helping your body use insulin more effectively, reducing the amount of sugar your liver makes, and decreasing the amount of sugar your body absorbs from food. Because it's extended-release, you usually take it once a day with your evening meal.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. Take your medication with meals to help your body absorb it properly. Even if you start to feel better, 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 and moisture. 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 regular 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 with your prescription and follow the instructions closely. Take your medication with meals to help your body absorb it properly. Even if you start to feel better, 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 and moisture. 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 regular 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 750mg once daily with your evening meal to reduce stomach upset and ensure proper 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 excessive alcohol can increase the risk of a serious side effect called lactic acidosis.
- Inform your doctor if you are scheduled for any X-ray procedures involving dye (contrast) or any surgery, as you may need to temporarily stop taking metformin.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
750 mg orally once daily with the evening meal
Dose Range:
500 - 2000 mg
Condition-Specific Dosing:
initialDose:
500 mg or 750 mg orally once daily with the evening meal. Dose may be increased by 500 mg weekly or 750 mg every other week, up to a maximum of 2000 mg once daily.
maximumDose:
2000 mg once daily
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established (Metformin XR is not approved for pediatric use; immediate-release metformin is approved for children ≥10 years)
Adolescent:
Not established (Metformin XR is not approved for pediatric use)
Dose Adjustments
Renal Impairment:
Mild:
eGFR 60-89 mL/min/1.73 m²: No dose adjustment generally needed. Monitor eGFR annually.
Moderate:
eGFR 45-59 mL/min/1.73 m²: Initiation of metformin is not recommended. If already on metformin, assess benefits/risks; consider dose reduction (e.g., 1000 mg/day max) and monitor eGFR every 3-6 months. eGFR 30-44 mL/min/1.73 m²: Initiation is contraindicated. If already on metformin, discontinue.
Severe:
eGFR <30 mL/min/1.73 m²: Contraindicated.
Dialysis:
Contraindicated in patients with end-stage renal disease (ESRD) or on dialysis due to increased risk of lactic acidosis.
Hepatic Impairment:
Mild:
Use with caution. Monitor liver function.
Moderate:
Not recommended due to increased risk of lactic acidosis.
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 (gluconeogenesis), 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 in monotherapy.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 50-60% (for immediate-release; XR absorption is slower and more prolonged)
Tmax:
7 hours (range 4-8 hours) for Glucophage XR 750 mg
FoodEffect:
Food prolongs Tmax and decreases Cmax for XR formulations, but overall extent of absorption (AUC) is similar or slightly increased. Should be taken with food to minimize gastrointestinal side effects.
Distribution:
Vd:
654 ± 358 L (for immediate-release)
ProteinBinding:
<5%
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 6.2 hours (plasma); 17.6 hours (blood) for immediate-release. For XR, effective half-life is longer due to extended absorption.
Clearance:
Renal clearance is approximately 3.5 times greater than creatinine clearance, indicating tubular secretion.
ExcretionRoute:
Renal (primarily unchanged in urine)
Unchanged:
>90%
Pharmacodynamics
OnsetOfAction:
Days to weeks for full therapeutic effect
PeakEffect:
Typically within 2-3 weeks of stable dosing
DurationOfAction:
Approximately 24 hours (for XR formulation)
Confidence:
High
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 promptly in a hospital setting. Prompt hemodialysis is recommended.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
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 can be characterized by:
+ 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 discuss any concerns with your doctor. Contact your doctor or seek medical help if you experience any of the following side effects or if they bother you or do not go away:
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, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
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 can be characterized by:
+ 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 discuss any concerns with your doctor. Contact your doctor or seek medical help if you experience any of the following side effects or if they bother you or do not go away:
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, consult 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:
- **Lactic Acidosis (SERIOUS):** Unusual muscle pain, trouble breathing, stomach pain, dizziness, lightheadedness, feeling cold, very tired or weak. Seek immediate medical attention.
- **Hypoglycemia (Low Blood Sugar):** (More likely if used with other diabetes medications) Sweating, shaking, fast heartbeat, hunger, blurred vision, dizziness, tingling hands/feet. Carry a source of sugar (e.g., glucose tablets, hard candy, fruit juice).
- **Vitamin B12 Deficiency:** Unusual tiredness, weakness, numbness or tingling in hands/feet (neuropathy).
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. Be sure to describe the allergic reaction you experienced, including any symptoms.
Certain health conditions, such as:
+ Acidic blood problems
+ Kidney disease
+ Liver disease
Recent medical events, including:
+ A heart attack
+ A stroke
Any difficulties with eating or drinking, including situations where you may be required to fast before a procedure or surgery.
* Upcoming or recent medical exams or tests that involve contrast agents, particularly if you have had one within the past 48 hours.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication with your existing health conditions and other medications. Never start, stop, or adjust the dosage of any medication without consulting your doctor first.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction you experienced, including any symptoms.
Certain health conditions, such as:
+ Acidic blood problems
+ Kidney disease
+ Liver disease
Recent medical events, including:
+ A heart attack
+ A stroke
Any difficulties with eating or drinking, including situations where you may be required to fast before a procedure or surgery.
* Upcoming or recent medical exams or tests that involve contrast agents, particularly if you have had one within the past 48 hours.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication with your existing health conditions and other medications. Never start, stop, or adjust the dosage of any medication without consulting your doctor first.
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, avoid driving, as it increases the risk of accidents. Monitor your blood sugar levels as instructed by your doctor. Additionally, follow your doctor's recommendations for regular blood tests to ensure your health is not affected.
During stressful periods, such as illness, infection, injury, or surgery, your blood sugar levels may be more challenging to control. Changes in physical activity, exercise, or diet can also impact your blood sugar. Adhere to the diet and exercise plan recommended by your doctor to maintain optimal blood sugar control.
If you experience diarrhea or vomiting, contact your doctor promptly, as you may need to increase 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 use of metformin may lead to decreased vitamin B-12 levels. If you have a history of low vitamin B-12 levels, consult 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 or concerns, discuss them with your doctor.
If you are 65 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 experience a renewed risk of pregnancy. To avoid pregnancy, use birth control while taking this medication.
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, avoid driving, as it increases the risk of accidents. Monitor your blood sugar levels as instructed by your doctor. Additionally, follow your doctor's recommendations for regular blood tests to ensure your health is not affected.
During stressful periods, such as illness, infection, injury, or surgery, your blood sugar levels may be more challenging to control. Changes in physical activity, exercise, or diet can also impact your blood sugar. Adhere to the diet and exercise plan recommended by your doctor to maintain optimal blood sugar control.
If you experience diarrhea or vomiting, contact your doctor promptly, as you may need to increase 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 use of metformin may lead to decreased vitamin B-12 levels. If you have a history of low vitamin B-12 levels, consult 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 or concerns, discuss them with your doctor.
If you are 65 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 experience a renewed risk of pregnancy. To avoid pregnancy, use birth control while taking this medication.
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 (severe metabolic acidosis with elevated lactate levels)
- Hypoglycemia (if co-ingested with other hypoglycemic agents or in specific conditions)
What to Do:
Call 911 or your local emergency number immediately. For advice, call a poison control center at 1-800-222-1222. Management involves supportive care and prompt hemodialysis to remove metformin and correct acidosis.
Drug Interactions
Contraindicated Interactions
- Iodinated contrast agents (temporarily discontinue at time of or prior to procedure and for 48 hours after, reinitiate only after renal function is stable)
- Alcohol (excessive acute or chronic intake due to increased risk of lactic acidosis)
- Drugs that increase risk of lactic acidosis (e.g., topiramate, zonisamide, carbonic anhydrase inhibitors)
Major Interactions
- Cimetidine (increases metformin plasma concentration by decreasing renal tubular secretion)
- Carbonic anhydrase inhibitors (e.g., acetazolamide, dichlorphenamide, topiramate, zonisamide - may increase risk of lactic acidosis)
- Drugs that affect renal function (e.g., NSAIDs, ACE inhibitors, ARBs, diuretics - may increase risk of lactic acidosis by impairing renal function)
- Verapamil (may decrease metformin exposure)
- Ranolazine (may increase metformin exposure)
Moderate Interactions
- Nifedipine (increases metformin absorption and excretion)
- Furosemide (increases metformin plasma and blood concentrations)
- Cationic drugs eliminated by renal tubular secretion (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin - may compete for renal tubular transport, increasing metformin levels)
- Drugs that cause hyperglycemia (e.g., corticosteroids, sympathomimetics, diuretics, thyroid products, phenothiazines, oral contraceptives, niacin - may require dose adjustment of metformin)
- Sulfonylureas, insulin, meglitinides (increased risk of hypoglycemia)
Minor Interactions
- Not specifically categorized as minor for metformin, but general caution with any drug affecting glucose levels.
Monitoring
Baseline Monitoring
Renal function (eGFR)
Rationale: To assess baseline kidney function and determine appropriate dosing or contraindication due to risk of lactic acidosis.
Timing: Prior to initiation of therapy.
HbA1c
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation of therapy.
Vitamin B12 levels
Rationale: Metformin can decrease vitamin B12 absorption.
Timing: Consider baseline, especially in patients at risk for deficiency.
Routine Monitoring
HbA1c
Frequency: Every 3-6 months
Target: Individualized, typically <7% for most adults
Action Threshold: If above target, consider dose adjustment or addition of other agents.
Renal function (eGFR)
Frequency: At least annually; more frequently (e.g., every 3-6 months) in elderly, those with impaired renal function, or during concomitant use of drugs affecting renal function.
Target: >60 mL/min/1.73 m² for full dose; >45 mL/min/1.73 m² for continued use with caution.
Action Threshold: If eGFR falls below 45 mL/min/1.73 m², reassess benefits/risks; if below 30 mL/min/1.73 m², discontinue.
Vitamin B12 levels
Frequency: Periodically (e.g., every 1-2 years) or if megaloblastic anemia or neuropathy is suspected.
Target: Normal range
Action Threshold: If low, consider supplementation.
Symptom Monitoring
- Symptoms of lactic acidosis (malaise, myalgia, respiratory distress, somnolence, abdominal distress, hypothermia, hypotension, bradyarrhythmias)
- Symptoms of hypoglycemia (if used with insulin or insulin secretagogues: sweating, tremor, dizziness, confusion, hunger, irritability)
- Gastrointestinal side effects (nausea, vomiting, diarrhea, abdominal discomfort)
Special Patient Groups
Pregnancy
Metformin is generally considered a preferred oral agent for the management of type 2 diabetes or gestational diabetes in pregnancy, especially if insulin is not desired or tolerated. While historically Category B, current guidelines often support its use when benefits outweigh risks. It crosses the placenta.
Trimester-Specific Risks:
First Trimester:
Limited data, but no clear evidence of increased risk of congenital malformations.
Second Trimester:
Often continued for glycemic control.
Third Trimester:
Often continued for glycemic control.
Lactation
Metformin is considered compatible with breastfeeding (L1 - safest). It is excreted into breast milk in small amounts, but infant exposure is low and adverse effects are not expected.
Infant Risk:
Low risk to infant.
Pediatric Use
Glucophage XR is not approved for use in pediatric patients. Immediate-release metformin is approved for children 10 years of age and older with type 2 diabetes.
Geriatric Use
Use with caution. Elderly patients are more likely to have decreased renal function, increasing the risk of lactic acidosis. Renal function should be assessed more frequently. The lowest effective dose should be used.
Clinical Information
Clinical Pearls
- Always take Glucophage XR with the evening meal to optimize absorption and minimize GI side effects.
- Patients may notice a 'ghost tablet' (the tablet shell) in their stool; this is normal and does not mean the medication was not absorbed.
- Counsel patients on the symptoms of lactic acidosis and the importance of seeking immediate medical attention if they occur.
- Emphasize the importance of temporary discontinuation of metformin before and after procedures involving iodinated contrast or surgery.
- Regular monitoring of renal function is paramount, especially in elderly patients or those with comorbidities.
- Consider periodic vitamin B12 level checks, especially in patients on long-term metformin therapy or those with risk factors for B12 deficiency.
Alternative Therapies
- Sulfonylureas (e.g., glipizide, glyburide, glimepiride)
- DPP-4 inhibitors (e.g., sitagliptin, saxagliptin)
- SGLT2 inhibitors (e.g., empagliflozin, canagliflozin)
- GLP-1 receptor agonists (e.g., liraglutide, semaglutide)
- Thiazolidinediones (e.g., pioglitazone)
- Insulin therapy
Cost & Coverage
Average Cost:
$30 - $150 per 30 tablets
Generic Available:
Yes
Insurance Coverage:
Tier 1 or Tier 2 (for generic metformin XR)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to 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 details about the overdose, including the medication taken, the amount, and the time it occurred.