Trijardy XR 5mg/2.5mg/1000mg Tabs
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 to lower the chance of death from heart disease in certain people.
Drug Class
Antidiabetic, Oral
Pharmacologic Class
SGLT2 Inhibitor; DPP-4 Inhibitor; Biguanide
Pregnancy Category
Not available
FDA Approved
Apr 2020
DEA Schedule
Not Controlled
Overview
What is this medicine?
Trijardy XR is a combination medicine used to treat type 2 diabetes. It contains three different medications that work in different ways to help lower your blood sugar. Empagliflozin helps your kidneys remove more sugar from your body. Linagliptin helps your body make more insulin when your blood sugar is high and reduces the amount of sugar your liver makes. Metformin 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 to you and follow the instructions closely.
Take your medication in the morning, with a meal.
Swallow the tablet whole; do not chew, break, crush, or dissolve it.
If you have trouble swallowing, consult your doctor for guidance.
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake.
Important Notes
You may notice what appears to be the tablet in your stool; this is normal and not a cause for concern.
If you have questions or concerns, discuss them with your doctor.
Continue taking your medication as directed by your doctor, even if you feel well.
Follow the diet and exercise plan recommended by your doctor.
If you are on a low-sodium or sodium-free diet, consult your doctor for guidance.
Regular blood tests are necessary; follow your doctor's instructions for scheduling these tests.
Discuss with your doctor which glucose tests are best for you to use.
Special Precautions
Be cautious in hot weather or when engaging in physical activity; drink plenty of fluids to avoid dehydration.
If you are unable to drink liquids or experience persistent stomach upset, vomiting, or diarrhea, contact your doctor for guidance to avoid dehydration, which can lead to low blood pressure or worsen kidney problems.
Stomach problems, such as upset stomach, vomiting, or diarrhea, are common when starting this medication. If you experience these symptoms later in your treatment, contact your doctor immediately, as they may be a sign of lactic acidosis.
Monitoring Your Condition
Blood sugar control may be more challenging during times of stress, such as fever, infection, injury, or surgery. Changes in physical activity, exercise, or diet can also affect blood sugar levels.
Monitor your blood sugar levels as directed by your doctor.
Interactions with Lab Tests
Inform all your healthcare providers and lab personnel that you are taking this medication, as it may affect certain lab tests.
Storage and Disposal
Store your medication at room temperature in a dry place, away from the bathroom.
Keep all medications in a safe location, out of 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. Consult your pharmacist for guidance on disposal or check for drug take-back programs in your area.
Missed Doses
If you miss a dose, take it as soon as you remember.
If it is close to the time for your next dose and you have already eaten, skip the missed dose and resume your regular schedule.
* Do not take two doses at the same time or extra doses.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely.
Take your medication in the morning, with a meal.
Swallow the tablet whole; do not chew, break, crush, or dissolve it.
If you have trouble swallowing, consult your doctor for guidance.
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake.
Important Notes
You may notice what appears to be the tablet in your stool; this is normal and not a cause for concern.
If you have questions or concerns, discuss them with your doctor.
Continue taking your medication as directed by your doctor, even if you feel well.
Follow the diet and exercise plan recommended by your doctor.
If you are on a low-sodium or sodium-free diet, consult your doctor for guidance.
Regular blood tests are necessary; follow your doctor's instructions for scheduling these tests.
Discuss with your doctor which glucose tests are best for you to use.
Special Precautions
Be cautious in hot weather or when engaging in physical activity; drink plenty of fluids to avoid dehydration.
If you are unable to drink liquids or experience persistent stomach upset, vomiting, or diarrhea, contact your doctor for guidance to avoid dehydration, which can lead to low blood pressure or worsen kidney problems.
Stomach problems, such as upset stomach, vomiting, or diarrhea, are common when starting this medication. If you experience these symptoms later in your treatment, contact your doctor immediately, as they may be a sign of lactic acidosis.
Monitoring Your Condition
Blood sugar control may be more challenging during times of stress, such as fever, infection, injury, or surgery. Changes in physical activity, exercise, or diet can also affect blood sugar levels.
Monitor your blood sugar levels as directed by your doctor.
Interactions with Lab Tests
Inform all your healthcare providers and lab personnel that you are taking this medication, as it may affect certain lab tests.
Storage and Disposal
Store your medication at room temperature in a dry place, away from the bathroom.
Keep all medications in a safe location, out of 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. Consult your pharmacist for guidance on disposal or check for drug take-back programs in your area.
Missed Doses
If you miss a dose, take it as soon as you remember.
If it is close to the time for your next dose and you have already eaten, skip the missed dose and resume your regular schedule.
* Do not take two doses at the same time or extra doses.
Lifestyle & Tips
- Take Trijardy XR exactly as prescribed by your doctor, usually once daily in the morning with a meal.
- Swallow the tablet whole; do not crush, cut, or chew it.
- Follow a healthy diet plan recommended by your doctor or dietitian.
- Engage in regular physical activity as advised by your doctor.
- Stay well-hydrated, especially when exercising or in hot weather, to reduce the risk of dehydration.
- Limit or avoid alcohol consumption, as it can increase the risk of lactic acidosis.
- Monitor your blood sugar levels regularly as instructed by your doctor.
- Inform your doctor if you are scheduled for any medical procedures, especially those involving iodinated contrast or surgery, as Trijardy XR may need to be temporarily stopped.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
One tablet orally once daily in the morning with a meal. The specific strength (e.g., 5mg empagliflozin/2.5mg linagliptin/1000mg metformin HCl extended-release) depends on the patient's current regimen and renal function.
Condition-Specific Dosing:
Initial Therapy:
Not indicated for initial therapy in patients with type 2 diabetes.
Switching from separate components:
Patients currently on empagliflozin, linagliptin, and/or metformin should be switched to Trijardy XR with a total daily dose of each component similar to their current regimen. Max daily doses: Empagliflozin 25 mg, Linagliptin 5 mg, Metformin HCl extended-release 2000 mg.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
eGFR 60 to <90 mL/min/1.73 m²: No dose adjustment for empagliflozin or linagliptin. Metformin dose may need adjustment based on individual response and tolerability, but generally no specific reduction required for mild impairment.
Moderate:
eGFR 45 to <60 mL/min/1.73 m²: No dose adjustment for empagliflozin or linagliptin. Metformin dose should not exceed 2000 mg/day. eGFR 30 to <45 mL/min/1.73 m²: Do not initiate Trijardy XR. If already on Trijardy XR, discontinue if eGFR persistently falls below 30 mL/min/1.73 m². Max metformin component 1000 mg/day.
Severe:
eGFR <30 mL/min/1.73 m²: Contraindicated.
Dialysis:
Contraindicated.
Hepatic Impairment:
Mild:
No dose adjustment for empagliflozin or linagliptin. Metformin: Use with caution.
Moderate:
No dose adjustment for empagliflozin or linagliptin. Metformin: Use with caution.
Severe:
Metformin is contraindicated. Trijardy XR is not recommended.
Pharmacology
Mechanism of Action
Trijardy XR combines three antihyperglycemic agents with complementary mechanisms of action: Empagliflozin (an SGLT2 inhibitor) reduces renal glucose reabsorption, leading to increased urinary glucose excretion. Linagliptin (a DPP-4 inhibitor) increases incretin hormone levels (GLP-1 and GIP), which enhances glucose-dependent insulin secretion and suppresses glucagon secretion. Metformin HCl (a biguanide) decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Pharmacokinetics
Absorption:
Bioavailability:
Empagliflozin: ~78%; Linagliptin: ~30% (oral); Metformin: ~50-60% (oral)
Tmax:
Empagliflozin: 1.5-2.5 hours; Linagliptin: 1.5 hours; Metformin XR: 7 hours (range 4-8 hours)
FoodEffect:
Empagliflozin: No clinically meaningful effect; Linagliptin: No clinically meaningful effect; Metformin XR: Food increases absorption (AUC and Cmax) but does not affect efficacy.
Distribution:
Vd:
Empagliflozin: 73.8 L; Linagliptin: 1640 L; Metformin: 654 L
ProteinBinding:
Empagliflozin: ~86.2%; Linagliptin: ~99% (at high concentrations, decreases to 75-89% at lower concentrations); Metformin: Negligible
CnssPenetration:
Limited for all components
Elimination:
HalfLife:
Empagliflozin: ~12.4 hours; Linagliptin: ~12 hours (terminal half-life); Metformin: ~6.2 hours (plasma), ~17.6 hours (blood)
Clearance:
Empagliflozin: 10.6 L/h; Linagliptin: 186 mL/min; Metformin: 488 mL/min (renal)
ExcretionRoute:
Empagliflozin: Renal (54.4%), Fecal (41.2%); Linagliptin: Fecal (80%), Renal (5%); Metformin: Renal (primarily unchanged)
Unchanged:
Empagliflozin: Not available; Linagliptin: ~80% (fecal), ~5% (renal); Metformin: >90% (renal)
Pharmacodynamics
OnsetOfAction:
Empagliflozin: Within hours; Linagliptin: Within hours; Metformin: Within days
PeakEffect:
Empagliflozin: 1.5-2.5 hours; Linagliptin: 1.5 hours; Metformin: 7 hours (XR)
DurationOfAction:
Empagliflozin: 24 hours; Linagliptin: 24 hours; Metformin: 24 hours (XR)
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 Trijardy XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended. Educate patients and their families about the symptoms of lactic acidosis and if these symptoms occur, to discontinue Trijardy XR and seek immediate medical attention. Risk factors for metformin-associated lactic acidosis 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
Serious Side Effects: Seek Medical Help Immediately
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 right away:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Difficulty breathing, swallowing, or talking
+ Unusual hoarseness or swelling of the mouth, face, lips, tongue, or throat
Signs of fluid and electrolyte problems, including:
+ Mood changes or confusion
+ Muscle pain or weakness
+ Abnormal or fast heartbeat
+ Severe dizziness or fainting
+ Increased thirst or seizures
+ Feeling extremely tired or weak
+ Decreased appetite
+ Difficulty urinating or changes in urine output
+ Dry mouth, dry eyes, or severe nausea and vomiting
Signs of pancreatitis (pancreas problems), such as:
+ Severe stomach pain
+ Severe back pain
+ Severe nausea and vomiting
Signs of kidney problems, including:
+ Difficulty urinating or changes in urine output
+ Blood in the urine
+ Sudden weight gain
Signs of a urinary tract infection (UTI), such as:
+ Blood in the urine
+ Burning or pain while urinating
+ Frequent or urgent need to urinate
+ Fever, lower stomach pain, or pelvic pain
Vaginal yeast infection: Report any itching, unusual odor, or discharge
Yeast infection of the penis: Report any pain, swelling, rash, or discharge
Severe joint pain: If you experience severe or persistent joint pain, contact your doctor right away
Low blood sugar: This medication may increase the risk of low blood sugar, especially when used with other diabetes medications. Signs of low blood sugar include:
+ Dizziness
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
If you experience any of these symptoms, contact your doctor immediately and follow their instructions for managing low blood sugar, which may include taking glucose tablets, liquid glucose, or some fruit juices.
Other Possible Side Effects
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 if they bother you or do not go away:
Signs of a common cold
Nose or throat irritation
Diarrhea or constipation
* Headache
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 right away:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Difficulty breathing, swallowing, or talking
+ Unusual hoarseness or swelling of the mouth, face, lips, tongue, or throat
Signs of fluid and electrolyte problems, including:
+ Mood changes or confusion
+ Muscle pain or weakness
+ Abnormal or fast heartbeat
+ Severe dizziness or fainting
+ Increased thirst or seizures
+ Feeling extremely tired or weak
+ Decreased appetite
+ Difficulty urinating or changes in urine output
+ Dry mouth, dry eyes, or severe nausea and vomiting
Signs of pancreatitis (pancreas problems), such as:
+ Severe stomach pain
+ Severe back pain
+ Severe nausea and vomiting
Signs of kidney problems, including:
+ Difficulty urinating or changes in urine output
+ Blood in the urine
+ Sudden weight gain
Signs of a urinary tract infection (UTI), such as:
+ Blood in the urine
+ Burning or pain while urinating
+ Frequent or urgent need to urinate
+ Fever, lower stomach pain, or pelvic pain
Vaginal yeast infection: Report any itching, unusual odor, or discharge
Yeast infection of the penis: Report any pain, swelling, rash, or discharge
Severe joint pain: If you experience severe or persistent joint pain, contact your doctor right away
Low blood sugar: This medication may increase the risk of low blood sugar, especially when used with other diabetes medications. Signs of low blood sugar include:
+ Dizziness
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
If you experience any of these symptoms, contact your doctor immediately and follow their instructions for managing low blood sugar, which may include taking glucose tablets, liquid glucose, or some fruit juices.
Other Possible Side Effects
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 if they bother you or do not go away:
Signs of a common cold
Nose or throat irritation
Diarrhea or constipation
* Headache
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, lightheadedness, feeling cold, or a slow/irregular heartbeat. Seek emergency medical help immediately.
- Symptoms of diabetic ketoacidosis (DKA): nausea, vomiting, stomach pain, excessive thirst, frequent urination, rapid weight loss, or unusual tiredness. Seek emergency medical help immediately.
- Symptoms of severe allergic reaction: rash, hives, swelling of your face, lips, tongue, or throat, or difficulty breathing or swallowing. Seek emergency medical help immediately.
- Symptoms of hypoglycemia (low blood sugar): sweating, trembling, dizziness, confusion, hunger, irritability. Carry a fast-acting sugar source (e.g., glucose tablets, fruit juice) to treat mild hypoglycemia.
- Symptoms of urinary tract infection (UTI): burning sensation when urinating, frequent urination, urgency, or pain in the lower abdomen. Contact your doctor.
- Symptoms of genital yeast infection: itching, redness, swelling, or unusual discharge in the genital area. Contact your doctor.
- Symptoms of dehydration: dizziness, lightheadedness, or fainting, especially when standing up.
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 to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances. 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.
The presence of any of the following health issues:
+ Acidic blood problem (acidosis)
+ Kidney disease
+ Liver disease
If you have recently experienced a heart attack or stroke.
If you are experiencing difficulties with eating or drinking, such as before undergoing a procedure or surgery.
If you are scheduled to undergo an exam or test that involves contrast media, or if you have had one within the past 48 hours, consult with your doctor.
If you are taking rifampin, as it may interact with this medication.
If you are pregnant or think you may be pregnant. Do not take this medication during the second or third trimester of pregnancy.
* If you are breast-feeding, as you should not breast-feed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you determine whether it is safe to take this medication in combination with your other treatments and health conditions. Never start, stop, or modify the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances. 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.
The presence of any of the following health issues:
+ Acidic blood problem (acidosis)
+ Kidney disease
+ Liver disease
If you have recently experienced a heart attack or stroke.
If you are experiencing difficulties with eating or drinking, such as before undergoing a procedure or surgery.
If you are scheduled to undergo an exam or test that involves contrast media, or if you have had one within the past 48 hours, consult with your doctor.
If you are taking rifampin, as it may interact with this medication.
If you are pregnant or think you may be pregnant. Do not take this medication during the second or third trimester of pregnancy.
* If you are breast-feeding, as you should not breast-feed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you determine whether it is safe to take this medication in combination with your other treatments and health conditions. Never start, stop, or modify 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.
To minimize the risk of dizziness or fainting, rise slowly from a sitting or lying position, and exercise caution when climbing stairs.
Do not operate a vehicle if your blood sugar levels are low, as this increases the risk of accidents.
Before consuming alcohol, consult with your doctor to discuss potential risks and interactions.
Long-term treatment with metformin may lead to decreased vitamin B-12 levels. If you have a history of low vitamin B-12 levels, discuss this with your doctor.
There is a risk of developing a severe and potentially life-threatening pancreas problem (pancreatitis) associated with this medication.
This drug may cause a condition called ketoacidosis, characterized by excessive acid in the blood or urine. This can be a life-threatening condition requiring hospitalization, even if your blood sugar levels are below 250. People with diabetes, pancreas problems, or those who are sick, dehydrated, or have a history of skipping meals are at a higher risk of developing ketoacidosis. Additionally, individuals on a ketogenic diet, undergoing surgery, or using insulin and missing doses are also at increased risk. Monitor your ketone levels as instructed by your doctor, and seek medical attention if you have any questions or concerns.
Severe urinary tract infections (UTIs) have been reported with this medication, and in some cases, hospitalization was necessary. Kidney problems may also occur, potentially requiring hospitalization or dialysis. A rare but potentially life-threatening infection can occur with this medication. Seek immediate medical attention if you experience tenderness, redness, or swelling in the genital area, accompanied by fever or a general feeling of illness.
A skin reaction called bullous pemphigoid has been associated with this medication, and in some cases, hospitalization was necessary. If you develop blisters or experience skin breakdown, contact your doctor immediately.
Heart failure has been reported in people taking this medication. If you have a history of heart failure or kidney problems, inform your doctor. Seek medical attention immediately if you experience extreme fatigue, shortness of breath, significant weight gain, or swelling in the arms or legs.
This medication may increase the risk of lower limb amputations, particularly toe and foot amputations. Discuss foot care with your doctor, and inform them if you have a history of amputations, blood vessel disease, nerve disease, or foot ulcers caused by diabetes. Seek medical attention immediately if you experience new pain, tenderness, sores, ulcers, or infections in your legs or feet.
If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects.
Women of childbearing age who have not been ovulating may be at risk of pregnancy. If you wish to avoid pregnancy, use birth control while taking this medication.
This medication may harm the unborn baby if taken during pregnancy. If you become pregnant or suspect you may be pregnant while taking this medication, contact your doctor immediately.
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
To minimize the risk of dizziness or fainting, rise slowly from a sitting or lying position, and exercise caution when climbing stairs.
Do not operate a vehicle if your blood sugar levels are low, as this increases the risk of accidents.
Before consuming alcohol, consult with your doctor to discuss potential risks and interactions.
Long-term treatment with metformin may lead to decreased vitamin B-12 levels. If you have a history of low vitamin B-12 levels, discuss this with your doctor.
There is a risk of developing a severe and potentially life-threatening pancreas problem (pancreatitis) associated with this medication.
This drug may cause a condition called ketoacidosis, characterized by excessive acid in the blood or urine. This can be a life-threatening condition requiring hospitalization, even if your blood sugar levels are below 250. People with diabetes, pancreas problems, or those who are sick, dehydrated, or have a history of skipping meals are at a higher risk of developing ketoacidosis. Additionally, individuals on a ketogenic diet, undergoing surgery, or using insulin and missing doses are also at increased risk. Monitor your ketone levels as instructed by your doctor, and seek medical attention if you have any questions or concerns.
Severe urinary tract infections (UTIs) have been reported with this medication, and in some cases, hospitalization was necessary. Kidney problems may also occur, potentially requiring hospitalization or dialysis. A rare but potentially life-threatening infection can occur with this medication. Seek immediate medical attention if you experience tenderness, redness, or swelling in the genital area, accompanied by fever or a general feeling of illness.
A skin reaction called bullous pemphigoid has been associated with this medication, and in some cases, hospitalization was necessary. If you develop blisters or experience skin breakdown, contact your doctor immediately.
Heart failure has been reported in people taking this medication. If you have a history of heart failure or kidney problems, inform your doctor. Seek medical attention immediately if you experience extreme fatigue, shortness of breath, significant weight gain, or swelling in the arms or legs.
This medication may increase the risk of lower limb amputations, particularly toe and foot amputations. Discuss foot care with your doctor, and inform them if you have a history of amputations, blood vessel disease, nerve disease, or foot ulcers caused by diabetes. Seek medical attention immediately if you experience new pain, tenderness, sores, ulcers, or infections in your legs or feet.
If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects.
Women of childbearing age who have not been ovulating may be at risk of pregnancy. If you wish to avoid pregnancy, use birth control while taking this medication.
This medication may harm the unborn baby if taken during pregnancy. If you become pregnant or suspect you may be pregnant while taking this medication, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Lactic acidosis (severe and potentially fatal)
- Hypoglycemia (if co-administered with insulin or sulfonylureas)
- Volume depletion/dehydration
- Abdominal discomfort, nausea, vomiting, diarrhea
What to Do:
In case of overdose, contact a poison control center (1-800-222-1222) or seek emergency medical attention immediately. Management is supportive and symptomatic. Hemodialysis can remove metformin and empagliflozin. Linagliptin is not significantly removed by dialysis.
Drug Interactions
Contraindicated Interactions
- Iodinated contrast agents (for metformin component - temporarily discontinue Trijardy XR 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 Trijardy XR if renal function is stable.)
Major Interactions
- Alcohol (increased risk of lactic acidosis with metformin)
- Diuretics (loop or thiazide) (increased risk of dehydration and hypotension with empagliflozin)
- Insulin and insulin secretagogues (e.g., sulfonylureas) (increased risk of hypoglycemia when co-administered with empagliflozin or linagliptin; dose reduction of insulin/sulfonylurea may be required)
- Rifampin (decreased linagliptin exposure, potentially reducing efficacy)
- Carbonic anhydrase inhibitors (e.g., topiramate, acetazolamide) (increased risk of lactic acidosis with metformin)
- Drugs that reduce metformin clearance (e.g., cimetidine, ranolazine, dolutegravir, isavuconazole, trimethoprim, vandetanib) (increased metformin exposure, increased risk of lactic acidosis)
Moderate Interactions
- ACE inhibitors/ARBs (increased risk of hypotension with empagliflozin, especially in volume-depleted patients)
- Corticosteroids (may increase blood glucose, requiring dose adjustment of Trijardy XR)
- Sympathomimetics (may increase blood glucose, requiring dose adjustment of Trijardy XR)
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Renal function (eGFR)
Rationale: To assess eligibility for treatment and guide dosing, especially for metformin and empagliflozin components.
Timing: Prior to initiation of therapy.
HbA1c
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation of therapy.
Blood Glucose (Fasting and Postprandial)
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation of therapy.
Volume status/Blood pressure
Rationale: To assess risk of hypotension, especially in elderly or those on diuretics.
Timing: Prior to initiation of therapy.
Routine Monitoring
Renal function (eGFR)
Frequency: At least annually; more frequently in patients at risk for renal impairment (e.g., elderly, those on certain medications).
Target: >30 mL/min/1.73 m²
Action Threshold: If eGFR falls below 45 mL/min/1.73 m², re-evaluate dose. If eGFR persistently falls below 30 mL/min/1.73 m², discontinue Trijardy XR.
HbA1c
Frequency: Every 3-6 months.
Target: Individualized, typically <7%
Action Threshold: If target not met, consider dose adjustment or additional therapy.
Blood Glucose (Fasting and Postprandial)
Frequency: Regularly, as advised by healthcare provider.
Target: Individualized
Action Threshold: Persistent hyperglycemia or hypoglycemia requires evaluation.
Vitamin B12 levels
Frequency: Periodically for patients on long-term metformin therapy, especially those with risk factors for deficiency.
Target: Normal range
Action Threshold: If low, consider supplementation.
Signs/symptoms of Lactic Acidosis
Frequency: Ongoing
Target: N/A
Action Threshold: If suspected (e.g., malaise, myalgia, respiratory distress, somnolence, abdominal distress), discontinue immediately and seek emergency medical attention.
Signs/symptoms of Diabetic Ketoacidosis (DKA)
Frequency: Ongoing
Target: N/A
Action Threshold: If suspected (e.g., nausea, vomiting, abdominal pain, rapid weight loss, thirst, polyuria, fatigue), discontinue immediately and seek emergency medical attention.
Signs/symptoms of Genital Mycotic Infections/UTIs
Frequency: Ongoing
Target: N/A
Action Threshold: If suspected, treat appropriately.
Symptom Monitoring
- Symptoms of lactic acidosis (e.g., unusual muscle pain, trouble breathing, stomach discomfort, dizziness, lightheadedness, irregular heartbeat, feeling cold)
- Symptoms of diabetic ketoacidosis (e.g., nausea, vomiting, abdominal pain, excessive thirst, frequent urination, rapid weight loss, fatigue, fruity breath)
- Symptoms of hypoglycemia (e.g., sweating, trembling, dizziness, confusion, hunger, irritability)
- Symptoms of urinary tract infection (e.g., burning sensation when urinating, frequent urination, urgency, pain in the lower abdomen)
- Symptoms of genital mycotic infection (e.g., itching, redness, swelling, discharge)
- Symptoms of dehydration/hypotension (e.g., dizziness, lightheadedness, fainting, especially upon standing)
Special Patient Groups
Pregnancy
Trijardy XR is not recommended during the second and third trimesters of pregnancy due to potential adverse effects on the developing fetal kidney from empagliflozin. Limited data on linagliptin and metformin use in pregnancy. Discuss risks and benefits with your doctor.
Trimester-Specific Risks:
First Trimester:
Limited human data. Metformin is often continued in pregnancy for gestational diabetes or PCOS, but the combination with empagliflozin and linagliptin is generally avoided.
Second Trimester:
Empagliflozin is not recommended due to potential for adverse renal effects in the fetus.
Third Trimester:
Empagliflozin is not recommended due to potential for adverse renal effects in the fetus.
Lactation
It is not known if Trijardy XR components are excreted in human milk. Due to the potential for serious adverse reactions in a breastfed infant, breastfeeding is not recommended while taking Trijardy XR.
Infant Risk:
Potential for serious adverse reactions (e.g., renal effects, hypoglycemia) in the infant. Unknown excretion into human milk.
Pediatric Use
Safety and effectiveness of Trijardy XR have not been established in pediatric patients. Not approved for use in patients younger than 18 years of age.
Geriatric Use
No dose adjustment is recommended based on age alone. However, older patients are more likely to have decreased renal function, be on diuretics, and be at higher risk for volume depletion and lactic acidosis. Renal function should be assessed more frequently in elderly patients.
Clinical Information
Clinical Pearls
- Trijardy XR is a once-daily combination tablet, which can improve patient adherence compared to multiple separate medications.
- Always assess renal function (eGFR) before initiating and periodically during treatment, as dosing is highly dependent on kidney function, especially for metformin and empagliflozin.
- Educate patients on the signs and symptoms of lactic acidosis and DKA, emphasizing the need for immediate medical attention if these occur.
- Advise patients to maintain adequate hydration to minimize the risk of volume depletion and hypotension, particularly in hot weather, during illness, or with diuretic use.
- Counsel patients on the increased risk of genital mycotic infections and urinary tract infections, and the importance of hygiene and prompt reporting of symptoms.
- Consider temporary discontinuation of Trijardy XR in situations that may increase the risk of lactic acidosis (e.g., surgery, iodinated contrast procedures, severe illness, dehydration).
Alternative Therapies
- Other SGLT2 inhibitors (e.g., canagliflozin, dapagliflozin, ertugliflozin)
- Other DPP-4 inhibitors (e.g., sitagliptin, saxagliptin, alogliptin)
- Other biguanides (Metformin monotherapy)
- GLP-1 receptor agonists (e.g., liraglutide, semaglutide, dulaglutide)
- Sulfonylureas (e.g., glipizide, glyburide)
- Thiazolidinediones (e.g., pioglitazone)
- Insulin therapy
Cost & Coverage
Average Cost:
$600 - $800 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 provides crucial information for patients. Please read this guide 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 healthcare provider. In the event of a suspected overdose, immediately call the poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the quantity, and the time it occurred.