Dapagliflo/metform 10mg-1000mg ER T
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 cotransporter 2 (SGLT2) inhibitor; Biguanide
Pregnancy Category
Not available
FDA Approved
Oct 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
This medication is a combination of two drugs, dapagliflozin and metformin, used to help control high blood sugar in adults with type 2 diabetes. 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.
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 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 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 want to explore local drug take-back programs.
What to Do If You Miss a Dose
If you miss a dose, follow these steps:
Take the missed dose as soon as you remember.
If it's almost time for your next dose, skip the missed dose and return to your regular 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 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.
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 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 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 want to explore local drug take-back programs.
What to Do If You Miss a Dose
If you miss a dose, follow these steps:
Take the missed dose as soon as you remember.
If it's almost time for your next dose, skip the missed dose and return to your regular 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 as advised by your healthcare provider.
- Maintain good hydration to prevent dehydration, especially when starting the medication or during illness.
- Limit or avoid excessive alcohol intake due to increased risk of lactic acidosis.
- Practice good personal hygiene, especially genital hygiene, to reduce the risk of infections.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: Dapagliflozin 5 mg/Metformin ER 500 mg orally once daily in the morning with food. Titrate based on efficacy and tolerability. Max: Dapagliflozin 10 mg/Metformin ER 2000 mg orally once daily.
Dose Range:
500 - 2000 mg
Condition-Specific Dosing:
Type 2 Diabetes Mellitus:
Initial: Dapagliflozin 5 mg/Metformin ER 500 mg orally once daily. May increase to Dapagliflozin 10 mg/Metformin ER 1000 mg, 1500 mg, or 2000 mg once daily. Max dose of metformin ER is 2000 mg/day. Max dose of dapagliflozin is 10 mg/day.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
eGFR 60 to <90 mL/min/1.73m2: No dose adjustment needed for either component. Monitor renal function periodically.
Moderate:
eGFR 45 to <60 mL/min/1.73m2: Initiate dapagliflozin 5 mg/day if not already on it. If eGFR falls to <45 mL/min/1.73m2 while on treatment, discontinue dapagliflozin. Metformin dose should be reduced by 50% (max 1000 mg/day). Monitor renal function every 3-6 months.
eGFR 30 to <45 mL/min/1.73m2: Not recommended to initiate dapagliflozin. Metformin dose should be reduced by 50% (max 1000 mg/day). Monitor renal function every 3 months.
Severe:
eGFR <30 mL/min/1.73m2: Contraindicated due to metformin component (increased risk of lactic acidosis).
Dialysis:
Contraindicated (metformin is substantially removed by hemodialysis, but risk of lactic acidosis remains high).
Hepatic Impairment:
Mild:
No dose adjustment for dapagliflozin. Metformin: Use with caution, monitor for lactic acidosis.
Moderate:
No dose adjustment for dapagliflozin. Metformin: Use with caution, monitor for lactic acidosis. Consider lower doses.
Severe:
No dose adjustment for dapagliflozin. Metformin: Not recommended due to increased risk of lactic acidosis.
Pharmacology
Mechanism of Action
Dapagliflozin is a highly potent and selective inhibitor of sodium-glucose cotransporter 2 (SGLT2) in the kidneys. By inhibiting SGLT2, dapagliflozin reduces glucose reabsorption from the glomerular filtrate, leading to increased urinary glucose excretion (glucosuria) and a reduction in blood glucose levels. Metformin is a biguanide that primarily acts by decreasing hepatic glucose production (gluconeogenesis and glycogenolysis), decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. It does not stimulate insulin secretion and therefore does not cause hypoglycemia in monotherapy.
Pharmacokinetics
Absorption:
Bioavailability:
Dapagliflozin: ~78%; Metformin ER: ~50-60% (variable)
Tmax:
Dapagliflozin: ~2 hours; Metformin ER: ~7 hours (range 4-8 hours)
FoodEffect:
Dapagliflozin: Food has a minimal effect on dapagliflozin exposure. Metformin ER: Food increases the extent of absorption (AUC) by approximately 50% and prolongs Tmax by 3 hours. Should be taken 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: Plasma elimination half-life ~6.2 hours (blood half-life ~17.6 hours)
Clearance:
Dapagliflozin: ~207 mL/min; Metformin: Renal clearance is ~3.5 times greater than creatinine clearance, indicating tubular secretion.
ExcretionRoute:
Dapagliflozin: Renal (75% as metabolites, 21% unchanged); Fecal (21% as metabolites, 2% unchanged). Metformin: Renal (primarily unchanged).
Unchanged:
Dapagliflozin: <1% in urine; Metformin: ~90% in urine
Pharmacodynamics
OnsetOfAction:
Dapagliflozin: Within hours (glucosuria); Metformin: Within days (glucose lowering)
PeakEffect:
Dapagliflozin: Peak glucosuria within 24 hours; Metformin: Peak glucose lowering effect typically within 2-3 weeks.
DurationOfAction:
Dapagliflozin: 24 hours; Metformin ER: 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 non-specific abdominal distress. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate/pyruvate ratio; metformin plasma levels generally >5 mcg/mL. If acidosis is suspected, discontinue Dapagliflozin/Metformin ER 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, having a radiological study 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, 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, including:
+ 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 changes in urine production
+ Dry mouth
+ Dry eyes
+ Severe upset stomach or vomiting
Signs of kidney problems, such as:
+ Unable to pass urine
+ Changes in urine production
+ Blood in the urine
+ Sudden weight gain
Signs of a urinary tract infection (UTI), including:
+ Blood in the urine
+ Burning or pain while urinating
+ 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 deadly infection: Seek medical help immediately if your genitals or the area between your genitals and rectum becomes tender, red, or swollen, and you have a fever or feel unwell
Low blood sugar: Be aware of signs such as dizziness, headache, feeling sleepy or weak, shaking, fast heartbeat, confusion, hunger, or 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 symptoms that bother you or do not go away, 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, including:
+ 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 changes in urine production
+ Dry mouth
+ Dry eyes
+ Severe upset stomach or vomiting
Signs of kidney problems, such as:
+ Unable to pass urine
+ Changes in urine production
+ Blood in the urine
+ Sudden weight gain
Signs of a urinary tract infection (UTI), including:
+ Blood in the urine
+ Burning or pain while urinating
+ 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 deadly infection: Seek medical help immediately if your genitals or the area between your genitals and rectum becomes tender, red, or swollen, and you have a fever or feel unwell
Low blood sugar: Be aware of signs such as dizziness, headache, feeling sleepy or weak, shaking, fast heartbeat, confusion, hunger, or 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 symptoms that bother you or do not go away, 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:
- Symptoms of lactic acidosis: unusual muscle pain, trouble breathing, stomach discomfort, dizziness, feeling cold, irregular heartbeat, unusual tiredness or weakness. Seek immediate medical attention.
- Symptoms of diabetic ketoacidosis (DKA): nausea, vomiting, abdominal pain, rapid and deep breathing, unusual tiredness or sleepiness, fruity breath odor. Seek immediate medical attention.
- Symptoms of dehydration: dizziness, lightheadedness, fainting, especially when standing up.
- Symptoms of urinary tract infection (UTI): burning sensation when urinating, frequent urination, urgency, pain in the lower abdomen or pelvis, blood in urine.
- Symptoms of genital yeast infection: itching, redness, swelling, rash, or unusual discharge in the genital area.
- Symptoms of hypoglycemia (low blood sugar): sweating, trembling, dizziness, confusion, hunger, irritability, headache, rapid heartbeat. If these occur, consume a quick source of sugar (e.g., glucose tablets, fruit juice).
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is crucial 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, such as foods or drugs. Describe the allergic reaction you experienced.
If you have type 1 diabetes, as this medication is not intended for its treatment.
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 before certain medical procedures or surgery.
If you are scheduled for or have had an exam or test that uses contrast media within the past 48 hours, consult with your doctor.
If you are taking or have recently taken immunosuppressive drugs for 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 not to breastfeed while taking this medication.
This list is not exhaustive, and it is essential to discuss all your medications (including prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other drugs and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is crucial 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, such as foods or drugs. Describe the allergic reaction you experienced.
If you have type 1 diabetes, as this medication is not intended for its treatment.
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 before certain medical procedures or surgery.
If you are scheduled for or have had an exam or test that uses contrast media within the past 48 hours, consult with your doctor.
If you are taking or have recently taken immunosuppressive drugs for 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 not to breastfeed while taking this medication.
This list is not exhaustive, and it is essential to discuss all your medications (including prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other drugs and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
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, and will advise 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 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. 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 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 with your doctor the consumption of alcohol, and adhere to the recommended diet and exercise plan. If you are on a low-salt or salt-free diet, consult with your doctor to ensure safe management of your condition.
Stress, Physical Activity, and Blood Sugar Control
Be aware that stress, changes in physical activity, exercise, or diet can impact blood sugar control. During periods of stress, such as fever, infection, injury, or surgery, it may be more challenging to manage blood sugar levels.
Hot Weather and Fluid Intake
In hot weather or during physical activity, drink plenty of fluids to prevent dehydration.
Vitamin B-12 Levels and Long-term Treatment
Long-term treatment with metformin may lead to low vitamin B-12 levels. If you have a history of low vitamin B-12 levels, discuss this with your doctor.
Risk of Ketoacidosis
This medication can increase the risk of ketoacidosis, a potentially life-threatening condition. 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 normal 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) and kidney problems have been reported with this medication. In some cases, hospitalization or dialysis may be necessary.
Dehydration and Kidney Problems
If you are unable to drink fluids or experience persistent vomiting, diarrhea, or stomach upset, consult your doctor to avoid dehydration. Dehydration can lead to low blood pressure or worsen kidney problems.
Tablet Appearance in Stool
You may notice the appearance of the tablet in your stool, which is a normal occurrence and not a cause for concern. If you have any questions, consult with your doctor.
Age-Related Precautions
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 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 are pregnant while taking this medication, contact your doctor immediately, as this medication may harm the unborn baby.
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, and will advise 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 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. 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 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 with your doctor the consumption of alcohol, and adhere to the recommended diet and exercise plan. If you are on a low-salt or salt-free diet, consult with your doctor to ensure safe management of your condition.
Stress, Physical Activity, and Blood Sugar Control
Be aware that stress, changes in physical activity, exercise, or diet can impact blood sugar control. During periods of stress, such as fever, infection, injury, or surgery, it may be more challenging to manage blood sugar levels.
Hot Weather and Fluid Intake
In hot weather or during physical activity, drink plenty of fluids to prevent dehydration.
Vitamin B-12 Levels and Long-term Treatment
Long-term treatment with metformin may lead to low vitamin B-12 levels. If you have a history of low vitamin B-12 levels, discuss this with your doctor.
Risk of Ketoacidosis
This medication can increase the risk of ketoacidosis, a potentially life-threatening condition. 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 normal 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) and kidney problems have been reported with this medication. In some cases, hospitalization or dialysis may be necessary.
Dehydration and Kidney Problems
If you are unable to drink fluids or experience persistent vomiting, diarrhea, or stomach upset, consult your doctor to avoid dehydration. Dehydration can lead to low blood pressure or worsen kidney problems.
Tablet Appearance in Stool
You may notice the appearance of the tablet in your stool, which is a normal occurrence and not a cause for concern. If you have any questions, consult with your doctor.
Age-Related Precautions
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 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 are 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 taken with insulin or sulfonylureas)
- Severe dehydration
- Hypotension
- Electrolyte imbalances
What to Do:
Call 1-800-222-1222 (Poison Control). Seek immediate medical attention. Management is supportive and symptomatic. Hemodialysis can be used to remove metformin and dapagliflozin.
Drug Interactions
Contraindicated Interactions
- Iodinated Contrast Agents (for metformin): Temporarily discontinue at the time of or prior to the procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m2, in patients with a history of liver disease, alcoholism, or heart failure, or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the procedure; restart metformin only if renal function is stable.
Major Interactions
- Alcohol: Potentiates the effect of metformin on lactate metabolism, increasing the risk of lactic acidosis. Advise patients to avoid excessive alcohol intake.
- Carbonic Anhydrase Inhibitors (e.g., topiramate, acetazolamide, zonisamide, dichlorphenamide): May increase the risk of lactic acidosis due to increased plasma metformin concentrations and/or direct effects on renal tubular acidosis. Consider more frequent monitoring.
- Drugs that reduce metformin clearance (e.g., cimetidine, ranolazine, dolutegravir, isavuconazole, trimethoprim, vandetanib): May increase metformin accumulation and the risk of lactic acidosis. Consider benefits and risks of concomitant use.
- Insulin and Insulin Secretagogues (e.g., sulfonylureas): Increased risk of hypoglycemia. A lower dose of insulin or insulin secretagogue may be required.
- Loop Diuretics (e.g., furosemide): May increase the risk of lactic acidosis by impairing renal function. Also, dapagliflozin can cause osmotic diuresis, increasing risk of dehydration and hypotension.
- ACE Inhibitors, Angiotensin Receptor Blockers (ARBs), NSAIDs: May increase the risk of renal impairment and lactic acidosis with metformin. Monitor renal function closely.
Moderate Interactions
- Lithium: SGLT2 inhibitors may decrease serum lithium concentrations. Monitor lithium levels.
- Digoxin: Dapagliflozin may slightly increase digoxin exposure. Monitor digoxin levels.
- Rifampin: May decrease dapagliflozin exposure. No dose adjustment needed but monitor glycemic control.
Minor Interactions
- Corticosteroids, Thiazide Diuretics, Phenothiazines, Thyroid Products, Estrogens, Oral Contraceptives, Phenytoin, Nicotinic Acid, Sympathomimetics, Calcium Channel Blocking Drugs, Isoniazid: May produce hyperglycemia and lead to loss of glycemic control. Monitor blood glucose.
Monitoring
Baseline Monitoring
Renal Function (eGFR)
Rationale: To assess eligibility for treatment and guide dosing adjustments, especially for metformin and dapagliflozin.
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
Vitamin B12 levels
Rationale: Metformin can decrease vitamin B12 levels.
Timing: Prior to initiation
Routine Monitoring
HbA1c
Frequency: Every 3-6 months
Target: <7% (individualized)
Action Threshold: >7% or not meeting individualized goals
Blood Glucose (Fasting and Postprandial)
Frequency: Daily (patient self-monitoring) or as clinically indicated
Target: Fasting: 80-130 mg/dL; Postprandial: <180 mg/dL (individualized)
Action Threshold: Consistently outside target range
Renal Function (eGFR)
Frequency: At least annually; more frequently (e.g., every 3-6 months) in patients with eGFR <60 mL/min/1.73m2, elderly, or those at risk of renal impairment.
Target: >60 mL/min/1.73m2 (ideally)
Action Threshold: eGFR <45 mL/min/1.73m2 (consider dapagliflozin discontinuation); eGFR <30 mL/min/1.73m2 (discontinue both)
Signs/Symptoms of Lactic Acidosis
Frequency: Continuously (patient education)
Target: N/A
Action Threshold: Any suspicion of lactic acidosis (e.g., malaise, myalgia, respiratory distress, somnolence, abdominal distress) requires immediate medical attention.
Signs/Symptoms of Dehydration/Hypotension
Frequency: Continuously (patient education)
Target: N/A
Action Threshold: Dizziness, lightheadedness, orthostatic hypotension, or signs of volume depletion.
Signs/Symptoms of Genital Mycotic Infections/UTIs
Frequency: Continuously (patient education)
Target: N/A
Action Threshold: Itching, discharge, dysuria, frequent urination.
Vitamin B12 levels
Frequency: Every 2-3 years or if megaloblastic anemia/neuropathy suspected
Target: Normal range
Action Threshold: Low levels (consider supplementation or alternative therapy)
Symptom Monitoring
- Symptoms of lactic acidosis (unusual muscle pain, trouble breathing, stomach discomfort, dizziness, feeling cold, irregular heartbeat, unusual tiredness or weakness)
- Symptoms of dehydration/volume depletion (dizziness, lightheadedness, fainting, orthostatic hypotension)
- Symptoms of urinary tract infection (burning sensation when urinating, frequent urination, urgency, pain in the lower abdomen or pelvis, blood in urine)
- Symptoms of genital mycotic infections (itching, redness, swelling, rash, discharge)
- Symptoms of hypoglycemia (sweating, trembling, dizziness, confusion, hunger, irritability, headache, rapid heartbeat)
- Symptoms of diabetic ketoacidosis (nausea, vomiting, abdominal pain, rapid and deep breathing, unusual tiredness or sleepiness, fruity breath odor)
Special Patient Groups
Pregnancy
Not recommended during the second and third trimesters of pregnancy due to potential adverse effects on fetal renal development associated with dapagliflozin. Metformin use during pregnancy should be individualized based on clinical need and risk-benefit assessment, but the combination product is generally avoided.
Trimester-Specific Risks:
First Trimester:
Limited human data for dapagliflozin. Metformin generally considered low risk.
Second Trimester:
Dapagliflozin: Potential for adverse renal effects in the developing fetus (renal tubular immaturity and permanent impairment). Not recommended.
Third Trimester:
Dapagliflozin: Potential for adverse renal effects in the developing fetus. Not recommended.
Lactation
Both dapagliflozin and metformin are excreted into human milk. Due to the potential for serious adverse reactions in a breastfed infant (e.g., hypoglycemia, renal effects), breastfeeding is not recommended during treatment.
Infant Risk:
L5 (Contraindicated/High Risk)
Pediatric Use
Safety and effectiveness have not been established in pediatric patients. Not indicated for use in patients younger than 18 years of age.
Geriatric Use
Elderly patients (âĨ65 years of age) are more likely to have decreased renal function and may be at increased risk for volume depletion and lactic acidosis. Renal function should be assessed more frequently. Initiate with lower doses and titrate carefully. Increased risk of fractures with SGLT2 inhibitors has been observed in some studies.
Clinical Information
Clinical Pearls
- This combination is particularly useful for patients with type 2 diabetes who need significant glycemic control and may benefit from the weight loss and cardiovascular/renal benefits associated with dapagliflozin.
- Always assess renal function (eGFR) before initiating and periodically during treatment, as both components have renal-dependent dosing and contraindications.
- Educate patients thoroughly on the symptoms of lactic acidosis and DKA, emphasizing the need for immediate medical attention if suspected.
- Advise patients to temporarily discontinue the medication before any radiological procedure involving iodinated contrast or major surgery.
- Ensure adequate hydration, especially in patients at risk for volume depletion (e.g., elderly, those on diuretics).
- Monitor for signs and symptoms of urinary tract infections and genital mycotic infections, which are common side effects of SGLT2 inhibitors.
Alternative Therapies
- Other SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, ertugliflozin)
- Other biguanides (metformin monotherapy)
- DPP-4 inhibitors (e.g., sitagliptin, saxagliptin, linagliptin)
- GLP-1 receptor agonists (e.g., liraglutide, semaglutide, dulaglutide)
- Sulfonylureas (e.g., glipizide, glyburide, glimepiride)
- Thiazolidinediones (e.g., pioglitazone, rosiglitazone)
- Insulin
Cost & Coverage
Average Cost:
Varies widely, typically $400-$700 per 30 tablets
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (preferred brand 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 and effective treatment, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, a patient fact sheet that provides crucial 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, 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. When seeking help, be prepared to provide details about the overdose, including the medication taken, the amount, and the time it occurred.