Xigduo XR 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, SGLT2 Inhibitor and Biguanide Combination
Pharmacologic Class
Sodium-glucose co-transporter 2 (SGLT2) inhibitor; Biguanide
Pregnancy Category
Not applicable (FDA has moved to risk summaries)
FDA Approved
Oct 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Xigduo XR is a combination medicine used to help control blood sugar levels in adults with type 2 diabetes. It contains two active ingredients: dapagliflozin, which helps your kidneys remove more sugar from your body through urine, and metformin, which helps your body use insulin better and reduces the amount of sugar your liver makes.
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 to help your body absorb it properly.
It's best to take your medication in the morning.
Swallow the tablet whole - do not chew, break, or crush it.
Drink plenty of non-caffeinated fluids, unless your doctor advises you to limit your fluid intake.
Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
To keep your medication effective and safe:
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 medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so by your doctor or pharmacist. If you're unsure about the best way to dispose 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 a 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 to help your body absorb it properly.
It's best to take your medication in the morning.
Swallow the tablet whole - do not chew, break, or crush it.
Drink plenty of non-caffeinated fluids, unless your doctor advises you to limit your fluid intake.
Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
To keep your medication effective and safe:
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 medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so by your doctor or pharmacist. If you're unsure about the best way to dispose 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 a missed one.
Lifestyle & Tips
- Follow a healthy diet plan as recommended by your doctor or dietitian.
- Engage in regular physical activity (e.g., 30 minutes of moderate exercise most days of the week).
- Limit alcohol intake, as it can increase the risk of lactic acidosis with metformin.
- Stay well-hydrated, especially when exercising or in hot weather, to reduce the risk of dehydration and kidney problems.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose: Dapagliflozin 5 mg/Metformin XR 500 mg orally once daily in the morning with food. Titrate gradually to the target dose. The strength 5mg/1000mg is a common maintenance dose.
Dose Range:
500 - 2000 mg
Condition-Specific Dosing:
Type 2 Diabetes Mellitus:
Individualize dosage based on effectiveness and tolerability, not exceeding 10 mg dapagliflozin and 2000 mg metformin XR daily. Administer once daily in the morning with food.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established (Safety and effectiveness not established in pediatric patients under 18 years of age)
Dose Adjustments
Renal Impairment:
Mild:
eGFR 60 to <90 mL/min/1.73m^2: No dose adjustment needed. Monitor renal function periodically.
Moderate:
eGFR 45 to <60 mL/min/1.73m^2: Initiation of Xigduo XR is not recommended. If patients are already on Xigduo XR and eGFR falls to <60, assess benefits/risks. eGFR 30 to <45 mL/min/1.73m^2: Discontinue Xigduo XR.
Severe:
eGFR <30 mL/min/1.73m^2: Contraindicated due to metformin component.
Dialysis:
Contraindicated due to metformin component.
Hepatic Impairment:
Mild:
No dose adjustment for dapagliflozin. Metformin: Use with caution; risk of lactic acidosis may be increased.
Moderate:
No dose adjustment for dapagliflozin. Metformin: Use with caution; risk of lactic acidosis may be increased.
Severe:
Not recommended for dapagliflozin. Metformin: Contraindicated due to increased risk of lactic acidosis.
Pharmacology
Mechanism of Action
Dapagliflozin: A sodium-glucose co-transporter 2 (SGLT2) inhibitor. It reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose (RTG), thereby increasing urinary glucose excretion (UGE). Metformin: A biguanide that decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves 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: No clinically meaningful effect; Metformin XR: Food increases absorption (AUC) by ~50% and Tmax is prolonged.
Distribution:
Vd:
Dapagliflozin: 118 L; Metformin: 654 Âą 358 L
ProteinBinding:
Dapagliflozin: ~91%; Metformin: Negligible (<5%)
CnssPenetration:
Limited for both
Elimination:
HalfLife:
Dapagliflozin: ~12.9 hours; Metformin: ~6.2 hours (plasma), ~17.6 hours (blood)
Clearance:
Dapagliflozin: 207 mL/min; Metformin: Renal clearance is ~3.5 times greater than creatinine clearance, indicating tubular secretion.
ExcretionRoute:
Dapagliflozin: Urine (75%), Feces (21%); Metformin: Urine (primarily unchanged)
Unchanged:
Dapagliflozin: <2% (urine); Metformin: ~90% (urine)
Pharmacodynamics
OnsetOfAction:
Dapagliflozin: Within hours (increased UGE); Metformin: Within days (glucose lowering)
PeakEffect:
Dapagliflozin: 1-2 weeks for maximal glucose lowering; Metformin: 2-3 weeks for maximal glucose lowering
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. If acidosis is suspected, discontinue Xigduo XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended. Risk factors include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors), age 65 years or greater, radiological studies with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
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
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 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 report any concerns to 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 concerns, 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 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
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 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 report any concerns to 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 concerns, 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 lactic acidosis: unusual muscle pain, trouble breathing, stomach discomfort, dizziness, lightheadedness, feeling cold, or a very slow or irregular heartbeat. Seek immediate medical attention.
- Signs of dehydration: dizziness, lightheadedness, or feeling faint, especially when standing up.
- Signs of urinary tract infection: burning sensation when urinating, frequent urination, urgency, or pain in the lower abdomen or back.
- Signs of genital yeast infection: itching, redness, swelling, or discharge in the genital area.
- Signs of Fournier's gangrene (a rare but serious infection): severe pain, tenderness, redness, or swelling in the genital or perineal area, accompanied by fever or feeling unwell. Seek immediate medical attention.
- Signs of ketoacidosis (rare): nausea, vomiting, stomach pain, excessive thirst, frequent urination, difficulty breathing, confusion, unusual sleepiness, or fruity-smelling breath. Seek immediate medical attention.
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 or have had an exam or test that uses contrast media within the past 48 hours, as you should discuss this 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, as you should not take this medication during the second or third trimester of pregnancy.
* If you are breastfeeding, as you should not breastfeed while taking this medication.
Additionally, it is crucial to provide your doctor and pharmacist with a comprehensive list of all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any health problems you have. This information will help ensure that it is safe for you to take this medication with your other drugs and health conditions. Never start, stop, or change the dose of any medication without first consulting 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 or have had an exam or test that uses contrast media within the past 48 hours, as you should discuss this 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, as you should not take this medication during the second or third trimester of pregnancy.
* If you are breastfeeding, as you should not breastfeed while taking this medication.
Additionally, it is crucial to provide your doctor and pharmacist with a comprehensive list of all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any health problems you have. This information will help ensure that it is safe for you to take this medication with your other drugs and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
Important Warnings and Precautions
It is crucial to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may advise you to stop taking this medication before certain surgical procedures. If you need to stop taking this medication, your doctor will provide guidance 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 the risk of accidents. To minimize the risk of dizziness or fainting, rise slowly from a sitting or lying down position, and exercise caution 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 certain lab test results, so it is essential 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. Additionally, monitor your blood sugar levels as instructed by your doctor.
Lifestyle Considerations
Before consuming alcohol, discuss the potential risks with your doctor. 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.
Stress and Blood Sugar Control
Be aware that stress, such as fever, infection, injury, or surgery, can affect blood sugar control. Changes in physical activity, exercise, or diet can also impact blood sugar levels. In hot weather or during physical activity, drink plenty of fluids to prevent dehydration.
Vitamin B12 Levels and Long-term Treatment
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 potentially life-threatening condition characterized by excessive acid in the blood or urine. This risk is higher in individuals with diabetes, pancreas problems, or those who are sick, dehydrated, or have undergone surgery. The risk is also increased in people who use insulin and take less than the prescribed dose or miss a dose. Monitor your ketone levels as directed by your doctor, and seek medical attention 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. If you experience dehydration, upset stomach, vomiting, or diarrhea that persists, contact your doctor for guidance to prevent dehydration and potential kidney problems.
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.
Age-Related Considerations
If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects.
Pregnancy and Birth Control
There is a potential risk of pregnancy in individuals of childbearing age who have not been ovulating. To avoid pregnancy, use birth control while taking this medication. If you become pregnant or suspect you may be pregnant while taking this medication, contact your doctor immediately, as this medication may harm the unborn baby.
It is crucial to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may advise you to stop taking this medication before certain surgical procedures. If you need to stop taking this medication, your doctor will provide guidance 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 the risk of accidents. To minimize the risk of dizziness or fainting, rise slowly from a sitting or lying down position, and exercise caution 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 certain lab test results, so it is essential 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. Additionally, monitor your blood sugar levels as instructed by your doctor.
Lifestyle Considerations
Before consuming alcohol, discuss the potential risks with your doctor. 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.
Stress and Blood Sugar Control
Be aware that stress, such as fever, infection, injury, or surgery, can affect blood sugar control. Changes in physical activity, exercise, or diet can also impact blood sugar levels. In hot weather or during physical activity, drink plenty of fluids to prevent dehydration.
Vitamin B12 Levels and Long-term Treatment
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 potentially life-threatening condition characterized by excessive acid in the blood or urine. This risk is higher in individuals with diabetes, pancreas problems, or those who are sick, dehydrated, or have undergone surgery. The risk is also increased in people who use insulin and take less than the prescribed dose or miss a dose. Monitor your ketone levels as directed by your doctor, and seek medical attention 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. If you experience dehydration, upset stomach, vomiting, or diarrhea that persists, contact your doctor for guidance to prevent dehydration and potential kidney problems.
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.
Age-Related Considerations
If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects.
Pregnancy and Birth Control
There is a potential risk of pregnancy in individuals of childbearing age who have not been ovulating. To avoid pregnancy, use birth control while taking this medication. If you become pregnant or suspect you may be pregnant while taking this medication, contact your doctor immediately, as this medication may harm the unborn baby.
Overdose Information
Overdose Symptoms:
- Lactic acidosis (most serious, due to metformin)
- Hypoglycemia (if used with insulin or sulfonylureas)
- Dehydration
- Hypotension
What to Do:
Call 911 or Poison Control (1-800-222-1222) immediately. Treatment is supportive. Hemodialysis is effective for removing metformin and its lactate. Dapagliflozin is minimally dialyzable.
Drug Interactions
Contraindicated Interactions
- Iodinated contrast agents (for metformin: temporarily discontinue at time of or prior to procedure in patients with eGFR between 30 and 60 mL/min/1.73 m^2, in patients with a history of liver disease, alcoholism, or heart failure, or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the procedure; restart metformin only if renal function is stable.)
- Severe renal impairment (eGFR <30 mL/min/1.73m^2)
Major Interactions
- Loop diuretics (e.g., furosemide): May increase risk of dehydration and hypotension with dapagliflozin; may affect metformin levels.
- Insulin and insulin secretagogues (e.g., 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): May increase metformin accumulation and risk of lactic acidosis.
- Alcohol: Potentiates the effect of metformin on lactate metabolism, increasing risk of lactic acidosis.
Moderate Interactions
- Thiazide diuretics: May reduce glucose-lowering effect of metformin.
- Corticosteroids, sympathomimetics, thyroid products: May increase blood glucose, requiring dose adjustment of Xigduo XR.
- ACE inhibitors/ARBs: May increase risk of hypotension with dapagliflozin.
- NSAIDs: May impair renal function, increasing risk of metformin accumulation.
Minor Interactions
- None commonly cited as minor for this combination with significant clinical impact.
Monitoring
Baseline Monitoring
Renal function (eGFR)
Rationale: To assess eligibility and baseline risk for metformin accumulation and dapagliflozin efficacy/safety.
Timing: Prior to initiation
HbA1c
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation
Liver function tests (LFTs)
Rationale: To assess baseline hepatic function, especially for metformin.
Timing: Prior to initiation
Volume status/Blood pressure
Rationale: To assess risk of hypotension/dehydration with dapagliflozin.
Timing: Prior to initiation
Routine Monitoring
HbA1c
Frequency: Every 3-6 months
Target: <7% (individualized)
Action Threshold: >7% (consider dose adjustment or additional therapy)
Renal function (eGFR)
Frequency: At least annually; more frequently in elderly, renally impaired, or with concomitant medications affecting renal function.
Target: >60 mL/min/1.73m^2 for optimal use; >45 mL/min/1.73m^2 for continued use; >30 mL/min/1.73m^2 for metformin continuation.
Action Threshold: eGFR <45 mL/min/1.73m^2 (consider discontinuation); eGFR <30 mL/min/1.73m^2 (discontinue)
Blood glucose (fasting and postprandial)
Frequency: Daily or as directed by physician
Target: Fasting: 80-130 mg/dL; Postprandial: <180 mg/dL (individualized)
Action Threshold: Persistent hyperglycemia or hypoglycemia
Signs/symptoms of lactic acidosis
Frequency: Ongoing patient education and monitoring
Target: N/A
Action Threshold: Any suspicion (e.g., malaise, myalgia, respiratory distress, abdominal pain) requires immediate medical attention.
Signs/symptoms of genitourinary infections or dehydration
Frequency: Ongoing patient education and monitoring
Target: N/A
Action Threshold: Any symptoms (e.g., dysuria, frequency, vaginal itching, dizziness, lightheadedness) require evaluation.
Symptom Monitoring
- Symptoms of lactic acidosis (unusual muscle pain, trouble breathing, stomach discomfort, dizziness, lightheadedness, feeling cold)
- Symptoms of dehydration (dizziness, lightheadedness, feeling faint, especially when standing up)
- Symptoms of urinary tract infection (burning sensation when urinating, frequent urination, urgency, pain in the lower abdomen or back)
- Symptoms of genital mycotic infection (itching, redness, swelling, discharge)
- Symptoms of hypoglycemia (shakiness, sweating, rapid heartbeat, blurred vision, confusion, hunger)
- Symptoms of Fournier's gangrene (pain, tenderness, redness, or swelling in the genital or perineal area, fever, malaise)
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 from dapagliflozin. Metformin is generally considered low risk, but current guidelines suggest insulin as the preferred agent for glycemic control in pregnancy.
Trimester-Specific Risks:
First Trimester:
Dapagliflozin: Limited human data, animal studies show no adverse effects at clinically relevant doses. Metformin: Limited human data, generally considered low risk, but not first-line.
Second Trimester:
Dapagliflozin: Not recommended due to potential for adverse renal effects in the developing fetus. Metformin: Generally considered low risk.
Third Trimester:
Dapagliflozin: Not recommended due to potential for adverse renal effects in the developing fetus. Metformin: Generally considered low risk.
Lactation
Both dapagliflozin and metformin are present in human milk. Due to the potential for serious adverse reactions in a breastfed infant (e.g., renal dysfunction, hypoglycemia), breastfeeding is not recommended while taking Xigduo XR.
Infant Risk:
Moderate risk (L3) - potential for renal dysfunction, hypoglycemia, and unknown long-term effects.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients under 18 years of age. Not recommended for use in this population.
Geriatric Use
Increased risk of renal impairment, dehydration, and lactic acidosis. Renal function should be assessed more frequently. Start with lower doses and titrate carefully. Avoid in patients âĨ80 years unless renal function is normal.
Clinical Information
Clinical Pearls
- Always take Xigduo XR with food in the morning to reduce gastrointestinal side effects of metformin and optimize absorption of the extended-release formulation.
- Educate patients thoroughly on the signs and symptoms of lactic acidosis, dehydration, and genitourinary infections, and when to seek immediate medical attention.
- Ensure adequate hydration, especially during illness, strenuous exercise, or in hot weather, to minimize the risk of dehydration and acute kidney injury.
- Temporarily discontinue Xigduo XR before any surgical procedures or radiological studies involving iodinated contrast agents, and restart only after renal function is stable.
- Monitor renal function (eGFR) regularly, as both components have renal considerations for dosing and contraindications.
- Xigduo XR is not indicated for type 1 diabetes or for the treatment of diabetic ketoacidosis.
Alternative Therapies
- Other SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, ertugliflozin)
- Other biguanides (e.g., metformin immediate-release)
- GLP-1 receptor agonists (e.g., semaglutide, liraglutide)
- DPP-4 inhibitors (e.g., sitagliptin, linagliptin)
- Sulfonylureas (e.g., glipizide, glyburide)
- Thiazolidinediones (e.g., pioglitazone)
- Insulin
Cost & Coverage
Average Cost:
$400 - $600 per 30 tablets
Insurance Coverage:
Tier 2 or Tier 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 safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which is a crucial patient fact sheet. Please read it carefully and review it again whenever you receive a refill. If you have any questions or concerns about this medication, consult 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. Be prepared to provide detailed information about the overdose, including the substance taken, the amount, and the time it occurred.