Xigduo XR 10mg/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 Agent, Combination
Pharmacologic Class
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor; Biguanide
Pregnancy Category
D
FDA Approved
Oct 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Xigduo XR is a medication used to help lower blood sugar in adults with type 2 diabetes. It contains two medicines: 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. This combination helps improve blood sugar control.
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 precisely.
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 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. If you're unsure about the best way to dispose of your medication, consult your pharmacist. 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, 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 resume 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 precisely.
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 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. If you're unsure about the best way to dispose of your medication, consult your pharmacist. 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, 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 resume 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 exactly as prescribed by your doctor, usually once daily in the morning with food.
- Swallow the tablet whole; do not crush, cut, or chew it.
- Maintain a healthy diet and exercise regularly 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 alcohol consumption, as it can increase the risk of a serious side effect called lactic acidosis.
- Inform your doctor if you are going to have any X-ray procedures involving dye (contrast media), as you may need to stop Xigduo XR temporarily.
- Carry identification indicating you have diabetes.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
10mg dapagliflozin/1000mg metformin XR orally once daily in the morning with food.
Dose Range:
5 - 10 mg
Condition-Specific Dosing:
initialDose:
Individualize based on patient's current regimen. For patients not currently on metformin, initiate with 5mg dapagliflozin/500mg metformin XR once daily.
maximumDose:
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/1.73m²: Initiate with 5mg dapagliflozin/500mg metformin XR once daily. Max dose 5mg dapagliflozin/1000mg metformin XR once daily. Monitor renal function every 3-6 months.
Moderate:
eGFR 30 to <45 mL/min/1.73m²: Not recommended to initiate. If already on, discontinue if eGFR persistently <45 mL/min/1.73m². Metformin is contraindicated.
Severe:
eGFR <30 mL/min/1.73m²: Contraindicated.
Dialysis:
Contraindicated.
Hepatic Impairment:
Mild:
No dose adjustment for dapagliflozin. Metformin: Use with caution.
Moderate:
No dose adjustment for dapagliflozin. Metformin: Use with caution.
Severe:
Metformin is contraindicated. Dapagliflozin: Not studied in severe impairment, use with caution.
Pharmacology
Mechanism of Action
Dapagliflozin: A sodium-glucose cotransporter 2 (SGLT2) inhibitor. It reduces renal glucose reabsorption and lowers the renal threshold for glucose (RTG), leading to increased urinary glucose excretion (glucosuria), thereby lowering blood glucose levels. Metformin: A biguanide that 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: ~2 hours; Metformin XR: ~4-8 hours
FoodEffect:
Dapagliflozin: No clinically meaningful effect; Metformin XR: Food increases absorption (AUC) by ~35% and Tmax is prolonged by 1 hour compared to fasting state.
Distribution:
Vd:
Dapagliflozin: ~118 L; Metformin: ~654 L
ProteinBinding:
Dapagliflozin: ~91%; Metformin: Negligible
CnssPenetration:
Limited
Elimination:
HalfLife:
Dapagliflozin: ~12.9 hours; Metformin: Plasma elimination half-life ~6.2 hours (blood half-life ~17.6 hours)
Clearance:
Dapagliflozin: ~2.07 L/hr; 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 (glucosuria); Metformin: Within days to weeks for full glucose-lowering effect
PeakEffect:
Dapagliflozin: Peak glucosuria within 24 hours; Metformin: Peak effect typically within 2-3 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. 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 clinicians on risk factors and symptoms of lactic acidosis. Instruct patients to discontinue Xigduo XR and seek immediate medical attention if symptoms occur. Xigduo XR is contraindicated in patients with an eGFR <30 mL/min/1.73m².
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, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of fluid and electrolyte problems, such as:
+ Mood changes
+ Confusion
+ Muscle pain or weakness
+ Fast or abnormal heartbeat
+ Severe dizziness or passing out
+ Increased thirst
+ Seizures
+ Feeling very tired or weak
+ Decreased appetite
+ Unable to pass urine or change in the amount of urine produced
+ Dry mouth
+ Dry eyes
+ Severe upset stomach or vomiting
Signs of kidney problems, such as:
+ Unable to pass urine
+ Change in how much urine is passed
+ Blood in the urine
+ Significant weight gain
Signs of a urinary tract infection (UTI), such as:
+ Blood in the urine
+ Burning or pain when passing urine
+ Frequent or urgent need to urinate
+ Fever
+ Lower stomach pain
+ Pelvic pain
Vaginal yeast infection: Report itching, bad 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 (an acid health problem in the blood)
A rare but potentially life-threatening infection: Get medical help right away if your genitals or the area between your genitals and rectum becomes tender, red, or swollen, and you have a fever or do not feel well
Low blood sugar: The risk may be increased when this medication is used with other diabetes medications. Signs may include:
+ Dizziness
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
+ Call your doctor right away if you experience any of these symptoms. Follow your doctor's instructions for managing low blood sugar, which may include taking glucose tablets, liquid glucose, or some fruit juices.
Other Possible Side Effects
Most people do not experience significant side effects, but some may occur. 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
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
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, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of fluid and electrolyte problems, such as:
+ Mood changes
+ Confusion
+ Muscle pain or weakness
+ Fast or abnormal heartbeat
+ Severe dizziness or passing out
+ Increased thirst
+ Seizures
+ Feeling very tired or weak
+ Decreased appetite
+ Unable to pass urine or change in the amount of urine produced
+ Dry mouth
+ Dry eyes
+ Severe upset stomach or vomiting
Signs of kidney problems, such as:
+ Unable to pass urine
+ Change in how much urine is passed
+ Blood in the urine
+ Significant weight gain
Signs of a urinary tract infection (UTI), such as:
+ Blood in the urine
+ Burning or pain when passing urine
+ Frequent or urgent need to urinate
+ Fever
+ Lower stomach pain
+ Pelvic pain
Vaginal yeast infection: Report itching, bad 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 (an acid health problem in the blood)
A rare but potentially life-threatening infection: Get medical help right away if your genitals or the area between your genitals and rectum becomes tender, red, or swollen, and you have a fever or do not feel well
Low blood sugar: The risk may be increased when this medication is used with other diabetes medications. Signs may include:
+ Dizziness
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
+ Call your doctor right away if you experience any of these symptoms. Follow your doctor's instructions for managing low blood sugar, which may include taking glucose tablets, liquid glucose, or some fruit juices.
Other Possible Side Effects
Most people do not experience significant side effects, but some may occur. 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
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of serious allergic reaction: rash, hives, swelling of face/lips/tongue/throat, difficulty breathing/swallowing.
- Signs of lactic acidosis (a serious side effect of metformin): unusual muscle pain, trouble breathing, stomach pain, dizziness, lightheadedness, feeling cold, very tired or weak.
- Signs of diabetic ketoacidosis (DKA): nausea, vomiting, stomach pain, excessive thirst, frequent urination, unusual tiredness, fruity-smelling breath.
- Signs of dehydration: dizziness, lightheadedness, feeling faint, especially when standing up.
- Signs of kidney problems: decreased urination, swelling in legs/feet.
- Signs of urinary tract infection (UTI): burning sensation when urinating, frequent urination, urgent need to urinate, pain in lower abdomen or back, blood in urine, fever.
- Signs of genital yeast infection (in women): vaginal itching, discharge, odor. (in men): rash or redness on penis, itching, swelling.
- Signs of Fournier's gangrene (a rare but serious genital infection): pain, tenderness, redness, or swelling in the genital or perineal area, fever, feeling unwell.
- Signs of low blood sugar (hypoglycemia) if taken with insulin or sulfonylureas: sweating, shaking, fast heartbeat, hunger, blurred vision, dizziness, tingling lips.
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 reaction you experienced, including the symptoms that occurred.
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, such as before a medical procedure or surgery.
If you are scheduled to undergo an exam or test that involves contrast agents, or if you have had such a test within the past 48 hours.
If you are taking or have recently taken immunosuppressive medications 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.
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. This will help identify any potential interactions between this medication and your other health conditions or treatments. Never start, stop, or change the dose of any medication without consulting your doctor first.
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 reaction you experienced, including the symptoms that occurred.
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, such as before a medical procedure or surgery.
If you are scheduled to undergo an exam or test that involves contrast agents, or if you have had such a test within the past 48 hours.
If you are taking or have recently taken immunosuppressive medications 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.
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. This will help identify any potential interactions between this medication and your other health conditions or treatments. Never start, stop, or change the dose of any medication without consulting your doctor first.
Precautions & Cautions
Important Warnings and Cautions
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 drug before certain surgical procedures, and will instruct you on when to resume taking it after the surgery or procedure.
Driving and Blood Sugar Levels
Do not operate a vehicle if your blood sugar levels are low, as this increases 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. Be aware that this medication may affect certain lab test results, so inform all your healthcare providers and lab personnel that you are taking this drug. Consult with your doctor to determine the most suitable glucose tests for you, and monitor your blood sugar levels as instructed.
Lifestyle Considerations
Before consuming alcohol, discuss the potential risks with your doctor. Adhere to the diet and exercise plan recommended by your doctor, and if you are on a low-salt or salt-free diet, consult with your doctor to ensure safe management. Be aware that stress, changes in physical activity, exercise, or diet may impact your blood sugar control.
Heat, Hydration, and Physical Activity
In hot weather or during physical activity, drink plenty of fluids to prevent dehydration. Be cautious and take regular breaks to avoid fluid loss.
Vitamin B12 Levels and Long-term Treatment
Long-term treatment with metformin may lead to decreased vitamin B12 levels. If you have a history of low vitamin B12 levels, discuss this with your doctor.
Risk of Ketoacidosis
This medication may 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. Additionally, people taking insulin who miss doses or take less than the prescribed amount are also at increased risk. 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 may also occur, which may necessitate hospitalization or dialysis.
Dehydration and Kidney Function
If you are unable to consume liquids orally or experience persistent vomiting, diarrhea, or stomach upset, contact your doctor to prevent dehydration. Dehydration can lead to low blood pressure or worsen existing 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 drug, contact your doctor immediately, as it 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 drug before certain surgical procedures, and will instruct you on when to resume taking it after the surgery or procedure.
Driving and Blood Sugar Levels
Do not operate a vehicle if your blood sugar levels are low, as this increases 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. Be aware that this medication may affect certain lab test results, so inform all your healthcare providers and lab personnel that you are taking this drug. Consult with your doctor to determine the most suitable glucose tests for you, and monitor your blood sugar levels as instructed.
Lifestyle Considerations
Before consuming alcohol, discuss the potential risks with your doctor. Adhere to the diet and exercise plan recommended by your doctor, and if you are on a low-salt or salt-free diet, consult with your doctor to ensure safe management. Be aware that stress, changes in physical activity, exercise, or diet may impact your blood sugar control.
Heat, Hydration, and Physical Activity
In hot weather or during physical activity, drink plenty of fluids to prevent dehydration. Be cautious and take regular breaks to avoid fluid loss.
Vitamin B12 Levels and Long-term Treatment
Long-term treatment with metformin may lead to decreased vitamin B12 levels. If you have a history of low vitamin B12 levels, discuss this with your doctor.
Risk of Ketoacidosis
This medication may 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. Additionally, people taking insulin who miss doses or take less than the prescribed amount are also at increased risk. 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 may also occur, which may necessitate hospitalization or dialysis.
Dehydration and Kidney Function
If you are unable to consume liquids orally or experience persistent vomiting, diarrhea, or stomach upset, contact your doctor to prevent dehydration. Dehydration can lead to low blood pressure or worsen existing 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 drug, contact your doctor immediately, as it may harm the unborn baby.
Overdose Information
Overdose Symptoms:
- Lactic acidosis (severe symptoms as above)
- Hypoglycemia (if taken with insulin/sulfonylureas)
- Severe dehydration
- Hypotension
What to Do:
Seek immediate medical attention. Call 911 or your local emergency number. For general advice, call a poison control center at 1-800-222-1222. Treatment is supportive and may include hemodialysis for metformin overdose.
Drug Interactions
Contraindicated Interactions
Major Interactions
- Carbonic anhydrase inhibitors (e.g., topiramate, zonisamide, acetazolamide, dichlorphenamide) - increased risk of lactic acidosis with metformin
- Diuretics (loop or thiazide) - increased risk of dehydration and hypotension with dapagliflozin; may also affect renal function and increase lactic acidosis risk with metformin
- Insulin and insulin secretagogues (e.g., sulfonylureas) - increased risk of hypoglycemia (dose reduction of insulin/secretagogue may be required)
- 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 - increased risk of hypotension with dapagliflozin, especially in volume-depleted patients
- Corticosteroids, sympathomimetics, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, calcium channel blockers, isoniazid - may cause hyperglycemia, requiring increased metformin dose
- NSAIDs - may impair renal function, increasing risk of metformin accumulation and lactic acidosis
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 guide dosing, as both components are renally cleared and metformin is contraindicated in severe renal impairment.
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/hydration
Rationale: To assess risk of hypotension and acute kidney injury with dapagliflozin.
Timing: Prior to initiation
Routine Monitoring
Renal function (eGFR)
Frequency: At least annually; more frequently (e.g., every 3-6 months) in patients with eGFR 30 to <60 mL/min/1.73m² or elderly patients, or when concomitant medications that may affect renal function are initiated.
Target: >60 mL/min/1.73m² for full dose; >45 mL/min/1.73m² for continued use (with caution)
Action Threshold: Discontinue if eGFR persistently <45 mL/min/1.73m²; contraindicated if <30 mL/min/1.73m².
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 postprandial)
Frequency: Regularly, as advised by healthcare provider
Target: Individualized
Action Threshold: Adjust therapy based on readings and symptoms.
Signs and symptoms of volume depletion (e.g., dizziness, orthostatic hypotension)
Frequency: Routinely, especially during initiation or with concomitant diuretics
Target: N/A
Action Threshold: Advise increased fluid intake, consider dose adjustment of diuretics or dapagliflozin.
Signs and symptoms of urinary tract infections (UTIs) or genital mycotic infections
Frequency: Routinely
Target: N/A
Action Threshold: Promptly evaluate and treat.
Vitamin B12 levels
Frequency: Annually for long-term metformin users, or if megaloblastic anemia suspected
Target: Normal range
Action Threshold: Supplement B12 if deficient.
Signs and symptoms of lactic acidosis
Frequency: Routinely, especially in patients with risk factors
Target: N/A
Action Threshold: Discontinue immediately and seek emergency medical attention.
Signs and symptoms of diabetic ketoacidosis (DKA)
Frequency: Routinely, especially if unwell or undergoing surgery
Target: N/A
Action Threshold: Promptly evaluate for DKA, even if blood glucose is not severely elevated (euglycemic DKA).
Symptom Monitoring
- Excessive thirst
- Frequent urination
- Dizziness
- Lightheadedness
- Fatigue
- Nausea
- Vomiting
- Abdominal pain
- Muscle cramps
- Unusual muscle pain
- Shortness of breath
- Weakness
- Unusual tiredness
- Foul-smelling or cloudy urine
- Painful urination
- Genital itching or discharge
- Pain, tenderness, redness, or swelling in the genital or perineal area (Fournier's gangrene)
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 the first trimester. Discuss risks and benefits with a healthcare provider.
Trimester-Specific Risks:
First Trimester:
Limited human data, animal studies with dapagliflozin show adverse renal effects at higher doses. Metformin is generally considered low risk in the first trimester.
Second Trimester:
Dapagliflozin: Not recommended due to potential for adverse renal development in the fetus.
Third Trimester:
Dapagliflozin: Not recommended due to potential for adverse renal development in the fetus.
Lactation
Not recommended during breastfeeding. Both dapagliflozin and metformin are excreted in breast milk. Potential for serious adverse reactions in a breastfed infant (e.g., renal dysfunction, hypoglycemia).
Infant Risk:
L3 (Moderate risk) for metformin; L4 (Potentially hazardous) for dapagliflozin. Overall, not recommended.
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
Use with caution in elderly patients due to increased risk of age-related decline in renal function and increased susceptibility to volume depletion. Renal function should be assessed more frequently. The risk of lactic acidosis with metformin increases with advancing age.
Clinical Information
Clinical Pearls
- Always take Xigduo XR with food to minimize gastrointestinal side effects of metformin and improve absorption of the XR component.
- Educate patients on the signs and symptoms of lactic acidosis and DKA, emphasizing that DKA can occur even with normal or mildly elevated blood glucose (euglycemic DKA).
- Stress the importance of adequate hydration to prevent volume depletion, especially in patients taking diuretics or those at risk of dehydration.
- Monitor renal function closely, particularly in elderly patients or those with pre-existing renal impairment, and adjust dose or discontinue as appropriate.
- Be aware of the increased risk of genital mycotic infections and urinary tract infections with SGLT2 inhibitors; counsel patients on hygiene and prompt reporting of symptoms.
- Temporarily discontinue Xigduo XR before any imaging procedures involving iodinated contrast media and before surgical procedures requiring restricted food and fluid intake.
- Consider vitamin B12 monitoring in patients on long-term metformin therapy, especially if neuropathy or anemia develops.
Alternative Therapies
- Other SGLT2 inhibitors (e.g., Jardiance, Farxiga, Invokana)
- Other biguanides (Metformin monotherapy)
- 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:
$500 - $700 per 30 tablets
Insurance Coverage:
Tier 2 or 3 (Brand-name drug, often requires prior authorization or step therapy)
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. Please read this guide carefully when you first receive your medication and review it again each time 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, immediately contact your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide detailed information about the overdose, including the name of the medication, the amount taken, and the time it occurred.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. Please read this guide carefully when you first receive your medication and review it again each time 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, immediately contact your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide detailed information about the overdose, including the name of the medication, the amount taken, and the time it occurred.