Xigduo XR 2.5mg/1000mg 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, Combination
Pharmacologic Class
Sodium-glucose cotransporter 2 (SGLT2) inhibitor and Biguanide
Pregnancy Category
Not assigned (risk in 2nd/3rd trimester)
FDA Approved
Oct 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Xigduo XR is a combination medicine that helps lower blood sugar in adults with type 2 diabetes. It contains two active ingredients: dapagliflozin and metformin. 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.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow these steps:
Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
Take your medication with food to help your body absorb it properly.
Take your dose in the morning to establish a consistent routine.
Swallow the medication whole - do not chew, break, or crush it.
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better. This will help ensure that you receive the full benefits of the treatment.
Storing and Disposing of Your Medication
To keep your medication safe and effective:
Store it at room temperature in a dry place, away from the bathroom.
Keep all medications in a secure location, out of the reach of children and pets.
Dispose of unused or expired medication properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your doctor or pharmacist.
Check with your pharmacist for guidance on the best way to dispose of your medication. You may also have access to drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose of your medication:
Take it as soon as you remember, unless it is close to the time for your next scheduled dose.
If it is almost time for your next dose, skip the missed dose and resume your regular dosing schedule.
* Do not take two doses at the same time or take extra doses to make up for a missed dose.
To get the most benefit from your medication, follow these steps:
Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
Take your medication with food to help your body absorb it properly.
Take your dose in the morning to establish a consistent routine.
Swallow the medication whole - do not chew, break, or crush it.
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better. This will help ensure that you receive the full benefits of the treatment.
Storing and Disposing of Your Medication
To keep your medication safe and effective:
Store it at room temperature in a dry place, away from the bathroom.
Keep all medications in a secure location, out of the reach of children and pets.
Dispose of unused or expired medication properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your doctor or pharmacist.
Check with your pharmacist for guidance on the best way to dispose of your medication. You may also have access to drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose of your medication:
Take it as soon as you remember, unless it is close to the time for your next scheduled dose.
If it is almost time for your next dose, skip the missed dose and resume your regular dosing schedule.
* Do not take two doses at the same time or take extra doses to make up for a missed dose.
Lifestyle & Tips
- 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.
- Stay well-hydrated to prevent dehydration, especially when sick or in hot weather.
- Limit alcohol intake, as it can increase the risk of lactic acidosis with metformin.
- Practice good hygiene to reduce the risk of genital and urinary tract infections.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
One Xigduo XR 2.5mg/1000mg tablet orally once daily in the morning with food.
Dose Range:
2.5 - 10 mg
Condition-Specific Dosing:
initial_therapy:
Initial dose is typically Xigduo XR 5mg/500mg or 5mg/1000mg once daily. For patients already on metformin, switch to Xigduo XR with a similar metformin dose and dapagliflozin 5mg or 10mg.
maximum_dose:
Maximum recommended daily dose is 10mg dapagliflozin and 2000mg metformin XR.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
eGFR 45 to <60 mL/min/1.73 m2: Initiation of Xigduo XR is not recommended. If already on Xigduo XR, continue with caution, monitor renal function.
Moderate:
eGFR <45 mL/min/1.73 m2: Contraindicated.
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: Not recommended due to increased risk of lactic acidosis.
Severe:
Not recommended for either component due to increased risk of lactic acidosis (metformin) and limited data (dapagliflozin).
Pharmacology
Mechanism of Action
Dapagliflozin is a highly potent and selective inhibitor of sodium-glucose cotransporter 2 (SGLT2) in the kidneys. By inhibiting SGLT2, it reduces glucose reabsorption from the glomerular filtrate, leading to increased urinary glucose excretion (glucosuria) and a reduction in blood glucose levels. Metformin, a biguanide, primarily acts by decreasing hepatic glucose production (gluconeogenesis), decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization.
Pharmacokinetics
Absorption:
Bioavailability:
Dapagliflozin: ~78%; Metformin: 50-60% (oral)
Tmax:
Dapagliflozin: 0.5-2 hours; Metformin XR: 4-8 hours
FoodEffect:
Dapagliflozin: Food has minimal effect on AUC, slightly prolongs Tmax. Metformin XR: Food increases absorption (AUC) by ~50% and prolongs Tmax, hence recommended with food.
Distribution:
Vd:
Dapagliflozin: 118 L; Metformin: 654 L
ProteinBinding:
Dapagliflozin: ~91%; Metformin: Negligible
CnssPenetration:
Limited for both
Elimination:
HalfLife:
Dapagliflozin: ~12.9 hours; Metformin: ~4.0-8.7 hours (plasma), ~17.6 hours (apparent terminal half-life for XR)
Clearance:
Dapagliflozin: 207 mL/min; Metformin: Renal clearance is ~3.5 times greater than creatinine clearance
ExcretionRoute:
Dapagliflozin: Urine (75%), Feces (21%); Metformin: Urine (primarily unchanged)
Unchanged:
Dapagliflozin: <1% (urine); Metformin: ~90% (urine)
Pharmacodynamics
OnsetOfAction:
Dapagliflozin: Within hours; Metformin: Within days
PeakEffect:
Dapagliflozin: 1-2 weeks for maximal glucosuric effect; Metformin: 2-3 weeks for maximal glucose-lowering effect
DurationOfAction:
Dapagliflozin: 24 hours; Metformin: 24 hours (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 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. If metformin-associated lactic acidosis is suspected, discontinue Xigduo XR and institute general supportive measures promptly in a hospital setting. Prompt hemodialysis is recommended. Educate patients and their clinicians about risk factors and symptoms of lactic acidosis, and counsel them to discontinue Xigduo XR and seek immediate medical attention if symptoms occur. Instruct patients to temporarily discontinue Xigduo XR for any clinical situation predisposing to hypoxemia, dehydration, or sepsis. Xigduo XR is contraindicated in patients with an eGFR less than 45 mL/min/1.73 m2.
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 stomach upset or 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 condition where the blood becomes too acidic).
Rare but Serious Infections
A rare but potentially life-threatening 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 their instructions 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. Many people may not experience any side effects or only minor ones. However, if you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical attention:
Diarrhea, upset stomach, or vomiting.
Headache.
Nose or throat irritation.
Reporting 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.
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 stomach upset or 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 condition where the blood becomes too acidic).
Rare but Serious Infections
A rare but potentially life-threatening 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 their instructions 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. Many people may not experience any side effects or only minor ones. However, if you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical attention:
Diarrhea, upset stomach, or vomiting.
Headache.
Nose or throat irritation.
Reporting 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:
- Signs of lactic acidosis: unusual muscle pain, trouble breathing, stomach pain, dizziness, lightheadedness, feeling cold, or very tired/weak.
- Signs of diabetic ketoacidosis (DKA): nausea, vomiting, stomach pain, excessive thirst, frequent urination, unusual tiredness, or fruity breath odor.
- Signs of dehydration: dizziness, lightheadedness, feeling faint, especially when standing up.
- Signs of urinary tract infection (UTI): burning sensation when urinating, frequent urination, cloudy or bloody urine, pain in the pelvis or back.
- Signs of genital yeast infection (females): vaginal itching, discharge, or odor. (males): rash or redness on the penis, itching, or swelling.
- Signs of Fournier's gangrene: severe pain, tenderness, redness, or swelling in the genital or perineal area, accompanied by fever or feeling unwell.
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 before starting this medication:
Any allergies you have, including allergies to this drug, its components, or other substances, and describe the symptoms 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 had a heart attack or stroke.
If you are experiencing difficulties with eating or drinking, including situations where you may need to fast before a procedure or surgery.
If you are scheduled for an exam or test that involves contrast agents, or if you have had one within the past 48 hours, consult with your doctor.
If you are taking or have recently taken immunosuppressive medications to treat kidney disease.
If you are pregnant or think you may be pregnant, as this medication should not be taken during the second or third trimester.
* If you are breastfeeding, as you should not breastfeed while taking this medication.
Additionally, it is crucial to discuss all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist to ensure safe use. Do not start, stop, or change the dose of any medication without first consulting your doctor. This list is not exhaustive, and you must verify that it is safe to take this medication with all your other medications and health conditions.
It is essential to inform your doctor about the following conditions or situations before starting this medication:
Any allergies you have, including allergies to this drug, its components, or other substances, and describe the symptoms 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 had a heart attack or stroke.
If you are experiencing difficulties with eating or drinking, including situations where you may need to fast before a procedure or surgery.
If you are scheduled for an exam or test that involves contrast agents, or if you have had one within the past 48 hours, consult with your doctor.
If you are taking or have recently taken immunosuppressive medications to treat kidney disease.
If you are pregnant or think you may be pregnant, as this medication should not be taken during the second or third trimester.
* If you are breastfeeding, as you should not breastfeed while taking this medication.
Additionally, it is crucial to discuss all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist to ensure safe use. Do not start, stop, or change the dose of any medication without first consulting your doctor. This list is not exhaustive, and you must verify that it is safe to take this medication with all your other medications and health conditions.
Precautions & Cautions
Important Warnings and Cautions
It is essential to inform all 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, rise slowly from a sitting or lying down position. Be cautious when climbing stairs.
Lab Tests and Monitoring
Regularly check your blood work and other lab tests as directed by your doctor. This medication may affect the results of certain lab tests, so it is crucial to inform all your healthcare providers and lab personnel that you are taking this medication. Consult with your doctor to determine the most suitable glucose tests for you to use.
Blood Sugar Monitoring 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 on a low-salt or salt-free diet, consult with your doctor to ensure safe management of your condition.
Managing Stress and Physical Activity
Be aware that stress, such as fever, infection, injury, or surgery, can affect your blood sugar control. Changes in physical activity, exercise, or diet can also impact your blood sugar levels.
Staying Hydrated
In hot weather or during physical activity, 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. The risk of ketoacidosis is higher in individuals with diabetes, pancreas problems, or those who are sick, dehydrated, or have undergone surgery. It is also increased in people who use insulin and take less than the prescribed dose or miss a dose. Regularly check your ketone levels as directed by your doctor, and consult with your doctor if you have any questions or concerns.
Urinary Tract Infections and Kidney Problems
Severe urinary tract infections (UTIs) have been reported with this medication, and in some cases, hospitalization was required. Kidney problems can also occur, which may necessitate hospitalization or dialysis.
Dehydration and Kidney Function
If you are unable to drink fluids or experience persistent vomiting, diarrhea, or stomach upset, you are at risk of dehydration. Dehydration can lead to low blood pressure or worsen kidney problems. Contact your doctor for guidance on managing these symptoms.
Tablet Appearance in Stool
You may notice the appearance of the tablet in your stool, which is a normal occurrence and not a cause for concern. If you have any questions, consult with your doctor.
Special Considerations
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. 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 essential to inform all 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, rise slowly from a sitting or lying down position. Be cautious when climbing stairs.
Lab Tests and Monitoring
Regularly check your blood work and other lab tests as directed by your doctor. This medication may affect the results of certain lab tests, so it is crucial to inform all your healthcare providers and lab personnel that you are taking this medication. Consult with your doctor to determine the most suitable glucose tests for you to use.
Blood Sugar Monitoring 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 on a low-salt or salt-free diet, consult with your doctor to ensure safe management of your condition.
Managing Stress and Physical Activity
Be aware that stress, such as fever, infection, injury, or surgery, can affect your blood sugar control. Changes in physical activity, exercise, or diet can also impact your blood sugar levels.
Staying Hydrated
In hot weather or during physical activity, 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. The risk of ketoacidosis is higher in individuals with diabetes, pancreas problems, or those who are sick, dehydrated, or have undergone surgery. It is also increased in people who use insulin and take less than the prescribed dose or miss a dose. Regularly check your ketone levels as directed by your doctor, and consult with your doctor if you have any questions or concerns.
Urinary Tract Infections and Kidney Problems
Severe urinary tract infections (UTIs) have been reported with this medication, and in some cases, hospitalization was required. Kidney problems can also occur, which may necessitate hospitalization or dialysis.
Dehydration and Kidney Function
If you are unable to drink fluids or experience persistent vomiting, diarrhea, or stomach upset, you are at risk of dehydration. Dehydration can lead to low blood pressure or worsen kidney problems. Contact your doctor for guidance on managing these symptoms.
Tablet Appearance in Stool
You may notice the appearance of the tablet in your stool, which is a normal occurrence and not a cause for concern. If you have any questions, consult with your doctor.
Special Considerations
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. 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 taken with insulin/sulfonylureas)
- Lactic acidosis (severe symptoms as described above)
- Severe dehydration
- Electrolyte imbalances
What to Do:
Seek immediate medical attention or call Poison Control at 1-800-222-1222. Treatment is supportive and symptomatic. Hemodialysis may be useful for metformin overdose.
Drug Interactions
Contraindicated Interactions
- Iodinated contrast agents (for metformin, temporarily discontinue)
- Patients with eGFR <45 mL/min/1.73 m2
Major Interactions
- Loop diuretics (increased risk of volume depletion and hypotension with dapagliflozin)
- Insulin and insulin secretagogues (sulfonylureas) (increased risk of hypoglycemia)
- Carbonic anhydrase inhibitors (e.g., topiramate, acetazolamide) (may increase risk of lactic acidosis with metformin)
- Drugs that reduce metformin clearance (e.g., cimetidine, ranolazine, dolutegravir, isavuconazonium, trimethoprim, vandetanib) (increased metformin levels and risk of lactic acidosis)
Moderate Interactions
- ACE inhibitors, ARBs (may increase risk of hypotension with dapagliflozin)
- NSAIDs (may worsen renal function, increasing metformin risk)
- Corticosteroids, thiazide diuretics, thyroid products, sympathomimetics (may cause hyperglycemia, requiring dose adjustment of Xigduo XR)
Monitoring
Baseline Monitoring
Renal function (eGFR)
Rationale: To assess eligibility for treatment and establish baseline for monitoring metformin and dapagliflozin clearance.
Timing: Prior to initiation
HbA1c
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation
Blood glucose (fasting and postprandial)
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation
Volume status/blood pressure
Rationale: To assess risk of hypotension/volume depletion with dapagliflozin.
Timing: Prior to initiation
Routine Monitoring
Renal function (eGFR)
Frequency: At least annually; more frequently in elderly, renally impaired, or with concomitant medications affecting renal function.
Target: >45 mL/min/1.73 m2 (for continued use)
Action Threshold: Discontinue if eGFR falls persistently below 45 mL/min/1.73 m2.
HbA1c
Frequency: Every 3-6 months
Target: Individualized, typically <7%
Action Threshold: Consider dose adjustment or additional therapy if target not met.
Blood glucose (fasting and/or self-monitoring)
Frequency: Daily to weekly, as needed
Target: Individualized
Action Threshold: Adjust diet/exercise, consider dose adjustment if out of range.
Signs/symptoms of volume depletion (e.g., dizziness, orthostasis)
Frequency: At each visit
Target: N/A
Action Threshold: Consider dose reduction, temporary interruption, or fluid intake increase.
Signs/symptoms of lactic acidosis (e.g., malaise, myalgia, somnolence, abdominal pain)
Frequency: At each visit
Target: N/A
Action Threshold: Immediately discontinue Xigduo XR and seek emergency medical attention.
Signs/symptoms of DKA (e.g., nausea, vomiting, abdominal pain, rapid breathing)
Frequency: At each visit
Target: N/A
Action Threshold: Immediately discontinue Xigduo XR and seek emergency medical attention.
Signs/symptoms of genitourinary infections (e.g., dysuria, frequency, itching, discharge)
Frequency: At each visit
Target: N/A
Action Threshold: Treat promptly, consider discontinuation if recurrent or severe.
Symptom Monitoring
- Hypoglycemia (especially with insulin/sulfonylureas)
- Lactic acidosis (malaise, myalgia, somnolence, abdominal pain, respiratory distress)
- Diabetic ketoacidosis (nausea, vomiting, abdominal pain, thirst, rapid breathing, confusion)
- Volume depletion/dehydration (dizziness, lightheadedness, orthostatic hypotension)
- Urinary tract infections (dysuria, frequency, urgency, fever)
- Genital mycotic infections (itching, redness, discharge)
- Fournier's gangrene (pain, tenderness, erythema, swelling in genital/perineal area)
- Hypersensitivity reactions (rash, urticaria, angioedema)
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 (based on animal data for dapagliflozin). Metformin use during pregnancy is generally considered safer than insulin in some cases, but Xigduo XR is not the primary choice.
Trimester-Specific Risks:
First Trimester:
Limited human data for dapagliflozin. Metformin generally considered low risk.
Second Trimester:
Dapagliflozin: Potential for adverse renal developmental effects (animal data). Metformin: Generally considered safe.
Third Trimester:
Dapagliflozin: Potential for adverse renal developmental effects (animal data). Metformin: Generally considered safe.
Lactation
Metformin is excreted into human milk. Dapagliflozin is excreted into milk in lactating rats; it is unknown if it is excreted in human milk. Due to the potential for serious adverse reactions in a breastfed infant, Xigduo XR is not recommended during breastfeeding.
Infant Risk:
Risk of lactic acidosis (metformin), unknown risk for dapagliflozin (potential for renal effects, hypoglycemia).
Pediatric Use
Safety and effectiveness have not been established in pediatric patients. Not recommended for use in patients younger than 18 years of age.
Geriatric Use
Increased risk of volume depletion, hypotension, and renal impairment with dapagliflozin. Increased risk of lactic acidosis with metformin due to age-related decline in renal function. Renal function should be assessed more frequently in elderly patients. Initiate with lower doses and titrate carefully.
Clinical Information
Clinical Pearls
- Always take Xigduo XR in the morning with food to reduce gastrointestinal side effects of metformin and optimize absorption of the XR formulation.
- Educate patients on the signs and symptoms of lactic acidosis and DKA, emphasizing the need for immediate medical attention if they occur.
- Advise patients to temporarily discontinue Xigduo XR before any surgical procedures, imaging studies with iodinated contrast, or in situations of severe illness (e.g., vomiting, diarrhea, fever) to reduce the risk of lactic acidosis and dehydration.
- Monitor renal function (eGFR) regularly, especially in elderly patients or those with pre-existing renal impairment, as dose adjustments or discontinuation may be necessary.
- Counsel patients on proper hydration to mitigate the risk of volume depletion and urinary tract infections associated with dapagliflozin.
- Consider the risk of genital mycotic infections and provide hygiene advice, especially for uncircumcised males and females.
Alternative Therapies
- Other SGLT2 inhibitors (e.g., Farxiga, Jardiance, Invokana)
- Other biguanides (e.g., 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
Cost & Coverage
Average Cost:
Not available (varies widely) per 30 tablets
Insurance Coverage:
Tier 2 or 3 (preferred or non-preferred brand)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure your safety, 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. Please read this guide carefully and review it again whenever you receive a refill of this medication. If you have any questions or concerns about this medication, we encourage you to discuss them with your doctor, 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.