Xigduo XR 5mg/500mg Tablets
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 help control blood sugar in people with type 2 diabetes.It is used in certain people to lower the risk of death and having to go to the hospital because of heart failure.It is used in people with certain kidney problems to lower the risk of worsening kidney problems.
Drug Class
Antidiabetic Agent
Pharmacologic Class
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor and Biguanide Combination
Pregnancy Category
Not available
FDA Approved
Oct 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Xigduo XR is a medication used to help manage blood sugar levels in adults with type 2 diabetes. It contains two medicines: dapagliflozin and metformin extended-release. Dapagliflozin works by helping your kidneys remove more sugar from your body through your urine. Metformin works by reducing the amount of sugar your liver makes and helping your body use insulin more effectively. This combination helps lower your blood sugar and can also help with weight loss and blood pressure.
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 food, preferably in the morning. Swallow the tablet whole - do not chew, break, or crush it. Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake.
It's essential to continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling better. This will help ensure that you receive the full benefits of the treatment.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom. Keep all medications in a safe location, out of the reach of children and pets. When your medication is no longer needed or has expired, dispose of it properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your doctor or pharmacist. If you have questions about disposing of your medication, consult with your pharmacist. You may also want to check if there are any drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. 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 food, preferably in the morning. Swallow the tablet whole - do not chew, break, or crush it. Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake.
It's essential to continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling better. This will help ensure that you receive the full benefits of the treatment.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom. Keep all medications in a safe location, out of the reach of children and pets. When your medication is no longer needed or has expired, dispose of it properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your doctor or pharmacist. If you have questions about disposing of your medication, consult with your pharmacist. You may also want to check if there are any drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take Xigduo XR once daily in the morning with food to reduce stomach upset and improve absorption of metformin XR.
- Swallow the tablet whole; do not crush, cut, or chew it.
- Follow a healthy diet plan recommended by your doctor or dietitian.
- Engage in regular physical activity as advised by your healthcare provider.
- Stay well-hydrated, especially when exercising or in hot weather, to reduce the risk of dehydration and kidney problems.
- Limit or avoid excessive alcohol intake, as it can increase the risk of a serious side effect called lactic acidosis.
- Monitor your blood sugar levels regularly as instructed by your doctor.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: Dapagliflozin 5 mg/Metformin XR 500 mg orally once daily in the morning with food. Titrate based on efficacy and tolerability. Max: Dapagliflozin 10 mg/Metformin XR 2000 mg once daily.
Dose Range:
500 - 2000 mg
Condition-Specific Dosing:
Type 2 Diabetes Mellitus:
Initial: Dapagliflozin 5 mg/Metformin XR 500 mg once daily. May increase Metformin XR component by 500 mg increments weekly to a maximum of 2000 mg. If already on Metformin, switch to the nearest therapeutically appropriate dose of Xigduo XR.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
eGFR 60 to <90 mL/min/1.73 m²: No dose adjustment needed. Continue to monitor renal function.
Moderate:
eGFR 45 to <60 mL/min/1.73 m²: Initiate with Dapagliflozin 5 mg/Metformin XR 500 mg once daily. Max dose of Metformin XR is 1000 mg once daily. If eGFR falls below 45 mL/min/1.73 m² while on treatment, discontinue Xigduo XR.
eGFR 30 to <45 mL/min/1.73 m²: Initiation is not recommended. If eGFR falls below 45 mL/min/1.73 m² while on treatment, discontinue Xigduo XR.
Severe:
eGFR <30 mL/min/1.73 m²: Contraindicated.
Dialysis:
Contraindicated.
Hepatic Impairment:
Mild:
No dose adjustment for dapagliflozin. Metformin: Use with caution, monitor for lactic acidosis.
Moderate:
No dose adjustment for dapagliflozin. Metformin: Use with caution, monitor for lactic acidosis.
Severe:
Not recommended due to increased risk of lactic acidosis with metformin.
Pharmacology
Mechanism of Action
Xigduo XR combines two antihyperglycemic agents with different mechanisms of action: Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and Metformin, a biguanide.
Dapagliflozin: Selectively inhibits SGLT2 in the renal proximal tubules, reducing glucose reabsorption and increasing urinary glucose excretion (glucosuria), thereby lowering blood glucose levels independently of insulin.
Metformin: Decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. It does not stimulate insulin secretion and therefore does not cause hypoglycemia in monotherapy.
Dapagliflozin: Selectively inhibits SGLT2 in the renal proximal tubules, reducing glucose reabsorption and increasing urinary glucose excretion (glucosuria), thereby lowering blood glucose levels independently of insulin.
Metformin: Decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves 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:
Dapagliflozin: ~78%; Metformin: 50-60% (oral)
Tmax:
Dapagliflozin: 0.5-2 hours; Metformin XR: 4-8 hours
FoodEffect:
Dapagliflozin: No clinically meaningful effect. Metformin XR: Food increases absorption (AUC) by approximately 50% and prolongs Tmax by 3 hours.
Distribution:
Vd:
Dapagliflozin: 118 L; Metformin: 654 ± 358 L
ProteinBinding:
Dapagliflozin: ~91%; Metformin: Negligible (<5%)
CnssPenetration:
Limited for both
Elimination:
HalfLife:
Dapagliflozin: ~12.9 hours; Metformin: ~6.2 hours (plasma, immediate release), ~8.7 hours (blood, immediate release); Metformin XR: ~9-17 hours (apparent terminal half-life)
Clearance:
Dapagliflozin: 207 mL/min; Metformin: Renal clearance is ~3.5 times greater than creatinine clearance, indicating tubular secretion.
ExcretionRoute:
Dapagliflozin: Urine (75% as metabolites, 21% as unchanged drug), Feces (21% as metabolites, 2.3% as unchanged drug). Metformin: Urine (primarily unchanged drug).
Unchanged:
Dapagliflozin: <1% (urine); Metformin: ~90% (urine)
Pharmacodynamics
OnsetOfAction:
Dapagliflozin: Within hours (glucosuria); Metformin: Within days to weeks for full glucose-lowering effect.
PeakEffect:
Dapagliflozin: Peak glucosuria within 24 hours; Metformin: Peak glucose lowering effect typically within 2 weeks.
DurationOfAction:
Dapagliflozin: 24 hours; Metformin XR: 24 hours
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 pain. 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 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 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.
If metformin-associated lactic acidosis is suspected, discontinue Xigduo XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.
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.
If metformin-associated lactic acidosis is suspected, discontinue Xigduo XR and institute general supportive measures 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 medical attention immediately:
Signs of an allergic reaction: 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, or swelling of the mouth, face, lips, tongue, or throat.
Signs of fluid and electrolyte problems: mood changes, confusion, muscle pain or weakness, fast or abnormal heartbeat, severe dizziness or fainting, increased thirst, seizures, feeling extremely tired or weak, decreased appetite, inability to urinate or changes in urine output, dry mouth, dry eyes, or severe nausea and vomiting.
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Signs of a urinary tract infection (UTI): blood in the urine, burning or pain while urinating, frequent or urgent need to urinate, fever, lower abdominal pain, or pelvic pain.
Vaginal yeast infection: report itching, unpleasant odor, or discharge.
Yeast infection of the penis: report pain, swelling, rash, or discharge.
Severe stomach pain.
Stomach problems that occur later during treatment, such as upset stomach, vomiting, or diarrhea, which may be a sign of lactic acidosis (a blood acid health problem).
Rare but Serious Infections
A rare but potentially deadly infection can occur with medications like this one. Seek medical help immediately if you experience:
Tender, red, or swollen genitals or the area between your genitals and rectum, accompanied by fever or feeling unwell.
Low Blood Sugar
Low blood sugar can occur, especially when this medication is used with other diabetes medications. Signs of low blood sugar may include:
Dizziness, headache, feeling sleepy or weak, shaking, fast heartbeat, confusion, hunger, or sweating.
If you experience any of these symptoms, contact your doctor right away and follow your prescribed plan for managing low blood sugar, 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. Common side effects include:
Diarrhea, upset stomach, or vomiting.
Headache.
Nose or throat irritation.
If you experience any of these side effects or any other symptoms that bother you or do not go away, contact your doctor for advice. 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 medical attention immediately:
Signs of an allergic reaction: 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, or swelling of the mouth, face, lips, tongue, or throat.
Signs of fluid and electrolyte problems: mood changes, confusion, muscle pain or weakness, fast or abnormal heartbeat, severe dizziness or fainting, increased thirst, seizures, feeling extremely tired or weak, decreased appetite, inability to urinate or changes in urine output, dry mouth, dry eyes, or severe nausea and vomiting.
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Signs of a urinary tract infection (UTI): blood in the urine, burning or pain while urinating, frequent or urgent need to urinate, fever, lower abdominal pain, or pelvic pain.
Vaginal yeast infection: report itching, unpleasant odor, or discharge.
Yeast infection of the penis: report pain, swelling, rash, or discharge.
Severe stomach pain.
Stomach problems that occur later during treatment, such as upset stomach, vomiting, or diarrhea, which may be a sign of lactic acidosis (a blood acid health problem).
Rare but Serious Infections
A rare but potentially deadly infection can occur with medications like this one. Seek medical help immediately if you experience:
Tender, red, or swollen genitals or the area between your genitals and rectum, accompanied by fever or feeling unwell.
Low Blood Sugar
Low blood sugar can occur, especially when this medication is used with other diabetes medications. Signs of low blood sugar may include:
Dizziness, headache, feeling sleepy or weak, shaking, fast heartbeat, confusion, hunger, or sweating.
If you experience any of these symptoms, contact your doctor right away and follow your prescribed plan for managing low blood sugar, 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. Common side effects include:
Diarrhea, upset stomach, or vomiting.
Headache.
Nose or throat irritation.
If you experience any of these side effects or any other symptoms that bother you or do not go away, contact your doctor for advice. 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:
- Signs of dehydration: feeling very thirsty, dry mouth, dizziness, lightheadedness, or fainting.
- Symptoms of a urinary tract infection (UTI): burning sensation when urinating, frequent urination, urgent need to urinate, pain in the lower abdomen or back, fever.
- Symptoms of a genital yeast infection: itching, redness, swelling, or discharge in the genital area.
- Symptoms of lactic acidosis (a serious and rare side effect): unusual muscle pain, trouble breathing, stomach discomfort, dizziness, lightheadedness, feeling cold, or a slow/irregular heartbeat. Seek emergency medical help immediately.
- Symptoms of ketoacidosis (a serious and rare side effect): nausea, vomiting, stomach pain, excessive thirst, frequent urination, unusual tiredness, or fruity-smelling breath. Seek emergency medical help immediately.
- Symptoms of low blood sugar (hypoglycemia): sweating, shaking, fast heartbeat, hunger, confusion, dizziness, or irritability (more likely if also taking insulin or sulfonylureas).
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 conditions or situations to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reactions you experienced.
If you have type 1 diabetes, as this medication is not intended to treat this condition.
If you have a condition that affects the acidity of your blood.
If you have kidney disease or are undergoing dialysis.
If you have liver disease.
If you have recently experienced a heart attack or stroke.
If you are unable to eat or drink normally, including situations before certain procedures or surgery.
If you are scheduled for an exam or test that involves contrast agents, or if you have had such a test within the past 48 hours, consult with your doctor.
If you are taking or have recently taken immunosuppressive drugs to treat kidney disease.
If you are pregnant or think you might be pregnant. Do not take this medication during the second or third trimester of pregnancy.
* If you are breastfeeding. It is recommended that you do not breastfeed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications (including prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other treatments and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following conditions or situations to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reactions you experienced.
If you have type 1 diabetes, as this medication is not intended to treat this condition.
If you have a condition that affects the acidity of your blood.
If you have kidney disease or are undergoing dialysis.
If you have liver disease.
If you have recently experienced a heart attack or stroke.
If you are unable to eat or drink normally, including situations before certain procedures or surgery.
If you are scheduled for an exam or test that involves contrast agents, or if you have had such a test within the past 48 hours, consult with your doctor.
If you are taking or have recently taken immunosuppressive drugs to treat kidney disease.
If you are pregnant or think you might be pregnant. Do not take this medication during the second or third trimester of pregnancy.
* If you are breastfeeding. It is recommended that you do not breastfeed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications (including prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other treatments and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
Precautions & Cautions
Important Information About Your Medication
It is crucial that you inform all of your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may instruct you to stop taking this medication before certain surgical procedures. If you are required to stop taking this medication, your doctor will advise you on when to resume taking it after your surgery or procedure.
Driving and Blood Sugar Levels
Do not operate a vehicle if your blood sugar levels are low, as this can increase your risk of being involved in an accident.
Preventing Dizziness and Falls
To minimize the risk of feeling dizzy or fainting, stand up slowly after sitting or lying down. Be cautious when climbing stairs, and have your blood work and other laboratory tests monitored as directed by your doctor.
Laboratory Tests and Medication Interactions
This medication may affect the results of certain laboratory tests. Inform all of your healthcare providers and laboratory personnel that you are taking this medication. Consult with your doctor to determine which glucose tests are most suitable for you.
Monitoring Blood Sugar Levels and Lifestyle
Monitor your blood sugar levels as instructed by your doctor. Discuss the consumption of alcohol with your doctor before drinking. Adhere to the diet and exercise plan recommended by your doctor. If you are following a low-sodium or sodium-free diet, consult with your doctor to ensure it is safe to do so.
Managing Blood Sugar Levels During Stressful Situations
It may be more challenging to control your blood sugar levels during periods of stress, such as illness, infection, injury, or surgery. Changes in physical activity, exercise, or diet can also impact your blood sugar levels.
Staying Hydrated
Be cautious in hot weather or when engaging in physical activity, and drink plenty of fluids to prevent dehydration.
Long-Term Treatment and Vitamin B12 Levels
Prolonged treatment with metformin may lead to low vitamin B12 levels. If you have a history of low vitamin B12 levels, discuss this with your doctor.
Risk of Ketoacidosis
This medication can increase the risk of ketoacidosis, a condition characterized by excessive acid in the blood or urine. This condition can be life-threatening and may require hospitalization. Ketoacidosis can occur even when blood sugar levels are below 250. Individuals with diabetes or pancreatic problems are at a higher risk of developing ketoacidosis. The risk is also increased in people who are ill, dehydrated, or unable to eat or drink normally, as well as those who follow a ketogenic diet or undergo surgery. Additionally, individuals who use insulin and take less than the prescribed dose or miss a dose are at a higher risk. Monitor your ketone levels as directed by your doctor, and consult with your doctor if you have any questions or concerns.
Risk of Severe Urinary Tract Infections
Severe urinary tract infections (UTIs) have been reported in individuals taking this medication, and in some cases, hospitalization was required.
Kidney Problems
Kidney problems can occur while taking this medication, and in some cases, hospitalization or dialysis may be necessary.
Dehydration and Kidney Problems
If you are unable to consume liquids orally or experience persistent vomiting, diarrhea, or stomach upset, it is essential to avoid dehydration. Consult with your doctor to determine the best course of action, as dehydration can lead to low blood pressure or worsen kidney problems.
Tablet Appearance in Stool
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.
Special Considerations for Older Adults
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
Pregnancy and Birth Control
There is a risk of pregnancy in individuals of childbearing age who have not been ovulating. If you wish to avoid pregnancy, use birth control while taking this medication. This medication can harm the unborn baby if taken during pregnancy. If you become pregnant or suspect you are pregnant while taking this medication, contact your doctor immediately.
It is crucial that you inform all of your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may instruct you to stop taking this medication before certain surgical procedures. If you are required to stop taking this medication, your doctor will advise you on when to resume taking it after your surgery or procedure.
Driving and Blood Sugar Levels
Do not operate a vehicle if your blood sugar levels are low, as this can increase your risk of being involved in an accident.
Preventing Dizziness and Falls
To minimize the risk of feeling dizzy or fainting, stand up slowly after sitting or lying down. Be cautious when climbing stairs, and have your blood work and other laboratory tests monitored as directed by your doctor.
Laboratory Tests and Medication Interactions
This medication may affect the results of certain laboratory tests. Inform all of your healthcare providers and laboratory personnel that you are taking this medication. Consult with your doctor to determine which glucose tests are most suitable for you.
Monitoring Blood Sugar Levels and Lifestyle
Monitor your blood sugar levels as instructed by your doctor. Discuss the consumption of alcohol with your doctor before drinking. Adhere to the diet and exercise plan recommended by your doctor. If you are following a low-sodium or sodium-free diet, consult with your doctor to ensure it is safe to do so.
Managing Blood Sugar Levels During Stressful Situations
It may be more challenging to control your blood sugar levels during periods of stress, such as illness, infection, injury, or surgery. Changes in physical activity, exercise, or diet can also impact your blood sugar levels.
Staying Hydrated
Be cautious in hot weather or when engaging in physical activity, and drink plenty of fluids to prevent dehydration.
Long-Term Treatment and Vitamin B12 Levels
Prolonged treatment with metformin may lead to low vitamin B12 levels. If you have a history of low vitamin B12 levels, discuss this with your doctor.
Risk of Ketoacidosis
This medication can increase the risk of ketoacidosis, a condition characterized by excessive acid in the blood or urine. This condition can be life-threatening and may require hospitalization. Ketoacidosis can occur even when blood sugar levels are below 250. Individuals with diabetes or pancreatic problems are at a higher risk of developing ketoacidosis. The risk is also increased in people who are ill, dehydrated, or unable to eat or drink normally, as well as those who follow a ketogenic diet or undergo surgery. Additionally, individuals who use insulin and take less than the prescribed dose or miss a dose are at a higher risk. Monitor your ketone levels as directed by your doctor, and consult with your doctor if you have any questions or concerns.
Risk of Severe Urinary Tract Infections
Severe urinary tract infections (UTIs) have been reported in individuals taking this medication, and in some cases, hospitalization was required.
Kidney Problems
Kidney problems can occur while taking this medication, and in some cases, hospitalization or dialysis may be necessary.
Dehydration and Kidney Problems
If you are unable to consume liquids orally or experience persistent vomiting, diarrhea, or stomach upset, it is essential to avoid dehydration. Consult with your doctor to determine the best course of action, as dehydration can lead to low blood pressure or worsen kidney problems.
Tablet Appearance in Stool
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.
Special Considerations for Older Adults
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
Pregnancy and Birth Control
There is a risk of pregnancy in individuals of childbearing age who have not been ovulating. If you wish to avoid pregnancy, use birth control while taking this medication. This medication can harm the unborn baby if taken during pregnancy. If you become pregnant or suspect you are pregnant while taking this medication, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Hypoglycemia (if co-administered with insulin/sulfonylureas)
- Lactic acidosis (for metformin component)
- Volume depletion/dehydration
- Hypotension
What to Do:
In case of overdose, contact a poison control center immediately (Call 1-800-222-1222). Treatment is symptomatic and supportive. Hemodialysis can remove dapagliflozin and metformin.
Drug Interactions
Contraindicated Interactions
- Iodinated Contrast Media (for Metformin component): Temporarily discontinue Xigduo XR 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 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 Xigduo XR if renal function is stable.
Major Interactions
- Loop Diuretics (e.g., Furosemide): May increase risk of dehydration and hypotension, and potentially acute kidney injury, especially in elderly or renally impaired patients. May also increase risk of lactic acidosis with metformin.
- Carbonic Anhydrase Inhibitors (e.g., Topiramate, Acetazolamide): May increase risk of lactic acidosis with metformin.
- Alcohol: Potentiates the effect of metformin on lactate metabolism, increasing the risk of lactic acidosis. Avoid excessive alcohol intake.
- Drugs that reduce metformin clearance (e.g., Cimetidine, Ranolazine, Dolutegravir, Isavuconazonium): May increase metformin accumulation and risk of lactic acidosis.
- Insulin and Insulin Secretagogues (e.g., Sulfonylureas): Increased risk of hypoglycemia when co-administered with dapagliflozin or metformin. Dose reduction of insulin/sulfonylurea may be required.
Moderate Interactions
- ACE Inhibitors/ARBs: May increase risk of hypotension and renal impairment with dapagliflozin.
- NSAIDs: May increase risk of renal impairment with dapagliflozin and metformin.
- Corticosteroids, Thiazide Diuretics, Phenothiazines, Thyroid Products, Estrogens, Oral Contraceptives, Phenytoin, Nicotinic Acid, Sympathomimetics, Calcium Channel Blocking Drugs, Isoniazid: May produce hyperglycemia, requiring dose adjustment of Xigduo XR.
- Verapamil: May reduce metformin effect.
Minor Interactions
- Not specifically listed as minor for this combination, but general caution with drugs affecting glucose levels.
Monitoring
Baseline Monitoring
Renal Function (eGFR)
Rationale: To assess eligibility for treatment and establish baseline for monitoring due to risk of acute kidney injury and metformin accumulation.
Timing: Prior to initiation of therapy.
HbA1c
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation of therapy.
Fasting Plasma Glucose (FPG)
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation of therapy.
Volume Status/Blood Pressure
Rationale: To assess risk of hypotension, especially in patients with impaired renal function, elderly patients, or those on diuretics.
Timing: Prior to initiation of therapy.
Vitamin B12 levels
Rationale: Metformin can decrease Vitamin B12 levels.
Timing: Prior to initiation of therapy, especially in patients at risk for deficiency.
Routine Monitoring
Renal Function (eGFR)
Frequency: At least annually; more frequently in patients at risk for renal impairment (e.g., elderly, those on diuretics, or with pre-existing renal disease).
Target: >60 mL/min/1.73 m² for full dose; >45 mL/min/1.73 m² for continued use (max 1000mg Metformin XR); >30 mL/min/1.73 m² for initiation of therapy (max 1000mg Metformin XR)
Action Threshold: Discontinue if eGFR falls persistently below 45 mL/min/1.73 m²; Contraindicated if eGFR <30 mL/min/1.73 m².
HbA1c
Frequency: Every 3-6 months, or as clinically indicated.
Target: Individualized, typically <7% for most adults.
Action Threshold: Consider dose adjustment or additional therapy if target not met.
Fasting Plasma Glucose (FPG)
Frequency: Regularly, as clinically indicated.
Target: Individualized, typically 80-130 mg/dL.
Action Threshold: Consider dose adjustment or additional therapy if target not met.
Signs/Symptoms of Volume Depletion
Frequency: Regularly, especially during initiation or dose increases.
Target: N/A
Action Threshold: Manage volume status; consider temporary discontinuation if severe.
Signs/Symptoms of Lactic Acidosis
Frequency: Ongoing.
Target: N/A
Action Threshold: Immediately discontinue and seek emergency medical attention if suspected.
Vitamin B12 levels
Frequency: Periodically, especially in patients with risk factors for deficiency or prolonged use of metformin.
Target: Normal range
Action Threshold: Supplement if deficient.
Symptom Monitoring
- Signs of dehydration (dizziness, lightheadedness, orthostatic hypotension)
- Symptoms of urinary tract infection (painful urination, frequent urination, urgency, fever)
- Symptoms of genital mycotic infection (itching, redness, discharge)
- Symptoms of lactic acidosis (unusual muscle pain, trouble breathing, stomach discomfort, dizziness, lightheadedness, feeling cold, irregular heartbeat)
- Symptoms of ketoacidosis (nausea, vomiting, abdominal pain, rapid deep breathing, unusual thirst, confusion, unusual fatigue, fruity breath odor)
- Symptoms of hypoglycemia (sweating, tremor, rapid heartbeat, hunger, confusion, dizziness, irritability) - especially if used with insulin or sulfonylureas.
Special Patient Groups
Pregnancy
Not recommended during the second and third trimesters of pregnancy due to potential adverse effects on renal development in the fetus. Limited data on use in pregnant women are insufficient to determine drug-associated risks for major birth defects or miscarriage. Metformin is generally considered safer than other oral antidiabetics during pregnancy, but insulin is often preferred for glycemic control.
Trimester-Specific Risks:
First Trimester:
Limited human data, animal studies show no direct developmental toxicity for dapagliflozin. Metformin is generally considered low risk.
Second Trimester:
Dapagliflozin: Avoid use. Animal studies show adverse renal developmental effects (renal pelvic and tubule dilatations) when exposed during periods of renal development corresponding to the second and third trimesters of human pregnancy.
Third Trimester:
Dapagliflozin: Avoid use. Animal studies show adverse renal developmental effects. Metformin: Generally considered low risk, but insulin is preferred for glycemic control.
Lactation
Not recommended. It is not known if dapagliflozin is excreted in human milk. Metformin is excreted in human milk in small amounts. Due to the potential for serious adverse reactions in a breastfed infant, including the potential for renal developmental effects from dapagliflozin, and the lack of data on long-term effects of metformin in breastfed infants, advise women not to breastfeed while taking Xigduo XR.
Infant Risk:
Potential for serious adverse reactions, including renal developmental effects (dapagliflozin) and unknown long-term effects (metformin).
Pediatric Use
Safety and effectiveness have not been established in pediatric patients under 18 years of age.
Geriatric Use
No dose adjustment is recommended based on age alone. However, older patients are more likely to have decreased renal function and be at higher risk for volume depletion and lactic acidosis. Assess renal function more frequently. Monitor volume status and consider lower doses of metformin if eGFR is borderline.
Clinical Information
Clinical Pearls
- Always take Xigduo XR in the morning with food to optimize metformin XR absorption and minimize GI side effects.
- Educate patients on the importance of hydration to mitigate the risk of volume depletion and acute kidney injury, especially during illness or hot weather.
- Counsel patients on the symptoms of lactic acidosis and ketoacidosis, emphasizing the need for immediate medical attention if suspected.
- Remind patients that the 'ghost tablet' (empty shell) may be seen in stool due to the extended-release formulation of metformin.
- Temporarily discontinue Xigduo XR before iodinated contrast imaging procedures, surgery, or other procedures that may lead to restricted food/fluid intake, and restart only after renal function is stable.
- Monitor for signs of urinary tract infections and genital mycotic infections, which are more common with SGLT2 inhibitors.
- Consider Vitamin B12 supplementation for patients on long-term metformin therapy, especially if they develop symptoms of deficiency (e.g., neuropathy, anemia).
Alternative Therapies
- Other SGLT2 inhibitors (e.g., Farxiga, Jardiance, Invokana)
- Other biguanides (Metformin IR)
- DPP-4 inhibitors (e.g., Januvia, Tradjenta)
- GLP-1 receptor agonists (e.g., Ozempic, Trulicity)
- Sulfonylureas (e.g., Glipizide, Glyburide)
- Thiazolidinediones (e.g., Pioglitazone)
- Insulin therapy
Cost & Coverage
Average Cost:
$500 - $700 per 30 tablets
Insurance Coverage:
Tier 2 or 3 (Preferred or Non-Preferred Brand)
General Drug Facts
If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure your safety and the effectiveness of your treatment, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. It is crucial to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about your medication, do not hesitate to discuss them with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, seek immediate medical attention or contact your local poison control center. When reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount consumed, and the time it occurred. This information will help healthcare professionals provide you with the most appropriate care and treatment.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. It is crucial to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about your medication, do not hesitate to discuss them with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, seek immediate medical attention or contact your local poison control center. When reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount consumed, and the time it occurred. This information will help healthcare professionals provide you with the most appropriate care and treatment.