Trijardy XR 12.5/2.5mg/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 Combination
Pharmacologic Class
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor, Dipeptidyl Peptidase-4 (DPP-4) Inhibitor, Biguanide
Pregnancy Category
Category C
FDA Approved
Sep 2020
DEA Schedule
Not Controlled
Overview
What is this medicine?
Trijardy XR is a combination medicine used to improve blood sugar control in adults with type 2 diabetes. It contains three different medicines: empagliflozin, which helps your kidneys remove more sugar from your body; linagliptin, which helps your body make more insulin when your blood sugar is high; and metformin, which helps reduce the amount of sugar your liver makes and improves how your body uses insulin.
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.
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 a tablet in your stool; this is normal and not a cause for concern. If you have questions, 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.
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 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.
Check 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 place, out of the reach of children and pets.
Dispose of unused or expired medications properly; do not flush them down the toilet or pour them down the drain unless instructed to do so. Consult your pharmacist for guidance on disposal or potential drug take-back programs in your area.
Missing a Dose
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.
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 a tablet in your stool; this is normal and not a cause for concern. If you have questions, 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.
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 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.
Check 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 place, out of the reach of children and pets.
Dispose of unused or expired medications properly; do not flush them down the toilet or pour them down the drain unless instructed to do so. Consult your pharmacist for guidance on disposal or potential drug take-back programs in your area.
Missing a Dose
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 once daily in the morning with food to reduce stomach upset.
- Follow a healthy diet plan as recommended by your doctor or dietitian.
- Engage in regular physical activity as advised by your healthcare provider.
- Stay well-hydrated, especially during illness, exercise, 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 lactic acidosis.
- Monitor your blood sugar levels regularly as instructed by your doctor.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
One Trijardy XR 12.5/2.5mg/1000mg tablet orally once daily in the morning with food.
Condition-Specific Dosing:
initial_therapy:
Not recommended as initial therapy for type 2 diabetes. Individualize dosing based on patient's current regimen and renal function.
maximum_dose:
Maximum daily doses: Empagliflozin 25mg, Linagliptin 5mg, Metformin 2000mg. The 12.5/2.5/1000mg strength contains the maximum daily dose of metformin for this combination.
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. Continue to monitor renal function.
Moderate:
eGFR 45 to <60 mL/min/1.73m²: Assess eGFR prior to initiation and at least annually. Do not initiate if eGFR is persistently <45 mL/min/1.73m². If eGFR falls below 45 mL/min/1.73m² while on therapy, assess benefits and risks of continuing. Discontinue if eGFR falls below 30 mL/min/1.73m².
Severe:
eGFR <30 mL/min/1.73m²: Contraindicated.
Dialysis:
Contraindicated in patients on dialysis.
Hepatic Impairment:
Mild:
No dose adjustment for empagliflozin or linagliptin. Use metformin with caution.
Moderate:
No dose adjustment for empagliflozin or linagliptin. Metformin is generally not recommended due to increased risk of lactic acidosis.
Severe:
Contraindicated due to metformin component (increased risk of lactic acidosis).
Pharmacology
Mechanism of Action
Trijardy XR combines three antihyperglycemic agents with complementary mechanisms of action:
1. **Empagliflozin:** A sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, leading to increased urinary glucose excretion and reduced plasma glucose concentrations.
2. **Linagliptin:** A dipeptidyl peptidase-4 (DPP-4) inhibitor that slows the inactivation of incretin hormones (GLP-1 and GIP), thereby increasing their active concentrations. This enhances glucose-dependent insulin secretion from pancreatic beta cells and decreases glucagon secretion from pancreatic alpha cells.
3. **Metformin:** A biguanide that primarily decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
1. **Empagliflozin:** A sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, leading to increased urinary glucose excretion and reduced plasma glucose concentrations.
2. **Linagliptin:** A dipeptidyl peptidase-4 (DPP-4) inhibitor that slows the inactivation of incretin hormones (GLP-1 and GIP), thereby increasing their active concentrations. This enhances glucose-dependent insulin secretion from pancreatic beta cells and decreases glucagon secretion from pancreatic alpha cells.
3. **Metformin:** A biguanide that primarily 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%; Metformin: 50-60%
Tmax:
Empagliflozin: 1.5-2 hours; Linagliptin: 1.5 hours; Metformin: 2-3 hours (immediate release), 7 hours (extended release)
FoodEffect:
Empagliflozin: No clinically meaningful effect; Linagliptin: No clinically meaningful effect; Metformin: Food decreases the extent and slightly delays the absorption of metformin XR, but this is not clinically significant for efficacy.
Distribution:
Vd:
Empagliflozin: 73.8 L; Linagliptin: 1640 L; Metformin: 654 L
ProteinBinding:
Empagliflozin: ~86%; Linagliptin: ~70-80%; Metformin: Negligible
CnssPenetration:
Limited for all components
Elimination:
HalfLife:
Empagliflozin: ~12.4 hours; Linagliptin: ~12 hours (terminal half-life ~100 hours due to tight binding to DPP-4); Metformin: ~6.2 hours (plasma), ~17.6 hours (blood)
Clearance:
Empagliflozin: 10.6 L/h; Linagliptin: 180 mL/min; Metformin: 488 mL/min (renal)
ExcretionRoute:
Empagliflozin: Renal (approx. 50%), Fecal (approx. 50%); Linagliptin: Fecal (approx. 80%), Renal (approx. 5%); Metformin: Renal (unchanged)
Unchanged:
Empagliflozin: ~50% (renal); Linagliptin: ~80% (fecal), ~5% (renal); Metformin: >90% (renal)
Pharmacodynamics
OnsetOfAction:
Empagliflozin: Within hours; Linagliptin: Within hours; Metformin: Within days
PeakEffect:
Empagliflozin: 1.5-2 hours; Linagliptin: 1.5 hours; Metformin: 2-3 hours (immediate release), 7 hours (extended release)
DurationOfAction:
Empagliflozin: 24 hours; Linagliptin: 24 hours; Metformin: 24 hours (extended release)
Safety & Warnings
BLACK BOX WARNING
Postmarketing cases of lactic acidosis, a serious metabolic complication that can result in death, have been reported in association with metformin. These cases had a sudden onset and were associated with a number of risk factors (e.g., significant renal impairment, concomitant use of certain drugs, age ≥65 years, having a radiological study with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, 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 immediate medical attention:
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, such as:
+ 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, such as:
+ Difficulty urinating
+ 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
Like all medications, this drug can cause side effects, although not everyone will experience them. 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 immediate medical attention:
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, such as:
+ 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, such as:
+ Difficulty urinating
+ 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
Like all medications, this drug can cause side effects, although not everyone will experience them. 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:
- **Lactic Acidosis (seek emergency care):** Unusual muscle pain, trouble breathing, stomach pain, dizziness, lightheadedness, feeling cold, irregular heartbeat, or unusual tiredness/weakness.
- **Diabetic Ketoacidosis (DKA) (seek emergency care):** Nausea, vomiting, stomach pain, excessive thirst, frequent urination, unusual tiredness, or fruity breath odor.
- **Hypoglycemia (low blood sugar):** Dizziness, sweating, confusion, tremor, hunger, rapid heartbeat. Carry a source of sugar (e.g., glucose tablets, juice) to treat mild symptoms.
- **Dehydration/Volume Depletion:** Dizziness, lightheadedness, especially when standing up.
- **Urinary Tract Infections (UTIs):** Burning sensation when urinating, frequent urination, urgency, pain in the lower abdomen or back, fever.
- **Genital Yeast Infections:** Itching, redness, swelling, or discharge in the genital area.
- **Serious Allergic Reactions:** Swelling of face, lips, tongue, or throat; difficulty breathing or swallowing; severe rash or itching.
- **Bullous Pemphigoid:** Large, fluid-filled blisters on the skin.
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.
Presence of any of the following health issues:
+ Acidic blood problem (acidosis)
+ Kidney disease
+ Liver disease
Recent heart attack or stroke
Inability to eat or drink normally, including situations before certain procedures or surgery
Upcoming or recent exams or tests involving contrast agents (within the past 48 hours)
Current use of rifampin
Pregnancy or potential pregnancy. Note that this medication should not be taken during the second or third trimester of pregnancy.
* 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 determine if it is safe to take this medication with your other treatments and health conditions. Never start, stop, or adjust the dosage of any medication without consulting your doctor first.
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.
Presence of any of the following health issues:
+ Acidic blood problem (acidosis)
+ Kidney disease
+ Liver disease
Recent heart attack or stroke
Inability to eat or drink normally, including situations before certain procedures or surgery
Upcoming or recent exams or tests involving contrast agents (within the past 48 hours)
Current use of rifampin
Pregnancy or potential pregnancy. Note that this medication should not be taken during the second or third trimester of pregnancy.
* 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 determine if it is safe to take this medication with your other treatments and health conditions. Never start, stop, or adjust the dosage of any medication without consulting your doctor first.
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 down position. Be cautious 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, inform 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 taking less than the prescribed dose or missing doses are also at increased risk. Monitor your ketone levels as instructed by your doctor, and consult with them 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, including those requiring hospitalization or dialysis, have also occurred. 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 notice your skin breaking down, 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 your 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 are pregnant while taking this medication, contact your doctor immediately.
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
To minimize the risk of dizziness or fainting, rise slowly from a sitting or lying down position. Be cautious 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, inform 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 taking less than the prescribed dose or missing doses are also at increased risk. Monitor your ketone levels as instructed by your doctor, and consult with them 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, including those requiring hospitalization or dialysis, have also occurred. 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 notice your skin breaking down, 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 your 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 are pregnant while taking this medication, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Lactic acidosis (most serious concern with metformin)
- Severe hypoglycemia (especially if co-administered with insulin/sulfonylureas)
- Severe dehydration
- Renal failure
What to Do:
Seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. Treatment is supportive and may include gastric lavage, hemodialysis (for metformin), and correction of metabolic abnormalities.
Drug Interactions
Contraindicated Interactions
- Iodinated contrast agents (for metformin): Temporarily discontinue Trijardy XR at the time of or prior to an iodinated contrast imaging 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 imaging procedure and restart Trijardy XR if renal function is stable.
- Alcohol (excessive acute or chronic use): Increases risk of lactic acidosis with metformin.
Major Interactions
- Carbonic Anhydrase Inhibitors (e.g., topiramate, zonisamide, acetazolamide, dichlorphenamide): May increase risk of lactic acidosis with metformin.
- Diuretics (loop or thiazide): May increase risk of dehydration and hypotension with empagliflozin, and may impair renal function, increasing metformin accumulation.
- Insulin and Insulin Secretagogues (e.g., sulfonylureas): Increased risk of hypoglycemia when co-administered with linagliptin and/or empagliflozin. Dose reduction of insulin or sulfonylurea may be required.
- Rifampin: Decreases linagliptin exposure, potentially reducing efficacy. Consider alternative agents.
Moderate Interactions
- Drugs that reduce metformin clearance (e.g., cimetidine, ranolazine, dolutegravir, isavuconazole, trimethoprim, vandetanib): May increase metformin accumulation and risk of lactic acidosis.
- Angiotensin-converting enzyme (ACE) inhibitors, Angiotensin receptor blockers (ARBs): Increased risk of hypotension and renal impairment when combined with empagliflozin.
- Corticosteroids, Sympathomimetics, Thiazides, other diuretics, Thyroid products, Estrogens, Oral contraceptives, Phenytoin, Nicotinic acid, Calcium channel blockers, Isoniazid: May cause hyperglycemia, requiring dose adjustment of Trijardy XR.
Minor Interactions
- Not specifically listed for minor interactions that require intervention beyond general monitoring.
Monitoring
Baseline Monitoring
Renal Function (eGFR)
Rationale: To assess eligibility for metformin and empagliflozin and to establish baseline for monitoring.
Timing: Prior to initiation of therapy.
HbA1c
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs)
Rationale: To assess for hepatic impairment, which is a contraindication for metformin.
Timing: Prior to initiation of therapy.
Vitamin B12 levels
Rationale: Metformin can decrease vitamin B12 levels.
Timing: Consider baseline measurement, especially in patients with risk factors for B12 deficiency.
Routine Monitoring
HbA1c
Frequency: Every 3-6 months
Target: Individualized, typically <7%
Action Threshold: If above target, consider dose adjustment or additional therapy.
Renal Function (eGFR)
Frequency: At least annually; more frequently in elderly, those with risk factors for renal impairment, or during concomitant use of drugs affecting renal function.
Target: >30 mL/min/1.73m²
Action Threshold: If eGFR falls below 45 mL/min/1.73m², reassess benefits/risks; discontinue if eGFR <30 mL/min/1.73m².
Signs/Symptoms of Lactic Acidosis
Frequency: Ongoing
Target: N/A
Action Threshold: If suspected (malaise, myalgia, respiratory distress, somnolence, abdominal pain), discontinue immediately and seek emergency medical attention.
Signs/Symptoms of Hypoglycemia
Frequency: Ongoing, especially with concomitant insulin/sulfonylureas
Target: N/A
Action Threshold: If symptomatic, treat with glucose. Adjust concomitant hypoglycemic agents if recurrent.
Signs/Symptoms of Urinary Tract Infections (UTIs) and Genital Mycotic Infections
Frequency: Ongoing
Target: N/A
Action Threshold: If suspected, obtain urine culture and treat appropriately. Consider discontinuation if severe or recurrent.
Volume Status/Blood Pressure
Frequency: Periodically, especially in patients prone to hypotension
Target: N/A
Action Threshold: If symptomatic hypotension or dehydration, manage volume status and consider dose adjustment or discontinuation.
Vitamin B12 levels
Frequency: Every 2-3 years, or if megaloblastic anemia is suspected
Target: Normal range
Action Threshold: If low, consider supplementation.
Symptom Monitoring
- Symptoms of lactic acidosis (e.g., malaise, myalgia, respiratory distress, somnolence, abdominal pain, unusual muscle pain)
- Symptoms of hypoglycemia (e.g., dizziness, sweating, confusion, tremor, hunger, rapid heartbeat)
- Symptoms of urinary tract infection (e.g., painful urination, frequent urination, urgency, fever, flank pain)
- Symptoms of genital mycotic infection (e.g., itching, redness, discharge, rash in genital area)
- Symptoms of dehydration/volume depletion (e.g., dizziness, lightheadedness, orthostatic hypotension)
- Symptoms of diabetic ketoacidosis (DKA) (e.g., rapid weight loss, nausea, vomiting, abdominal pain, excessive thirst, rapid deep breathing, unusual tiredness, fruity breath odor)
- Symptoms of bullous pemphigoid (e.g., large, fluid-filled blisters on the skin)
Special Patient Groups
Pregnancy
Generally not recommended during the second and third trimesters due to potential adverse renal effects on the developing fetus from empagliflozin. Metformin is often continued in pregnancy if needed for glycemic control, but the combination with empagliflozin and linagliptin is not typically used.
Trimester-Specific Risks:
First Trimester:
Limited human data. Animal studies with empagliflozin show renal pelvic and ureter dilation at high doses. Metformin is generally considered low risk.
Second Trimester:
Empagliflozin is not recommended due to potential for adverse renal effects (impaired renal development and function) in the fetus.
Third Trimester:
Empagliflozin is not recommended due to potential for adverse renal effects (impaired renal development and function) in the fetus.
Lactation
Metformin is generally considered compatible with breastfeeding. However, empagliflozin and linagliptin are excreted in animal milk, and there is insufficient data in human milk. Due to potential for serious adverse reactions in a breastfed infant, breastfeeding is not recommended while taking Trijardy XR.
Infant Risk:
Risk of adverse renal effects (empagliflozin), unknown effects (linagliptin). Metformin is generally low risk.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients. Not indicated for use in patients under 18 years of age.
Geriatric Use
Use with caution due to increased likelihood of decreased renal function in elderly patients. Renal function should be assessed more frequently. Elderly patients may be at higher risk for volume depletion and lactic acidosis. Start with lower doses and titrate slowly.
Clinical Information
Clinical Pearls
- Trijardy XR is a once-daily extended-release tablet that must be swallowed whole and not crushed, cut, or chewed.
- Take with food in the morning to minimize gastrointestinal side effects associated with metformin.
- Educate patients thoroughly on the signs and symptoms of lactic acidosis, DKA, and hypoglycemia, and when to seek immediate medical attention.
- Emphasize the importance of hydration to mitigate the risk of volume depletion and UTIs/genital infections associated with empagliflozin.
- Temporarily discontinue Trijardy XR before iodinated contrast imaging procedures or surgery due to the metformin component.
- Monitor renal function closely, especially in elderly patients or those with risk factors for kidney impairment, as dose adjustments or discontinuation may be necessary.
Alternative Therapies
- Other SGLT2 inhibitors (e.g., Farxiga, Invokana)
- Other DPP-4 inhibitors (e.g., Tradjenta, Januvia, Onglyza)
- Other biguanides (Metformin monotherapy)
- GLP-1 receptor agonists (e.g., Ozempic, Trulicity, Victoza)
- Insulin
- Sulfonylureas (e.g., Glipizide, Glyburide)
- Thiazolidinediones (e.g., Pioglitazone)
- Alpha-glucosidase inhibitors (e.g., Acarbose)
- Meglitinides (e.g., Repaglinide)
Cost & Coverage
Average Cost:
Varies widely, typically $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 your safety, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which is a crucial patient fact sheet. Please read it carefully and review it again whenever you receive a refill. If you have any questions or concerns about this medication, we encourage you to discuss them with your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide detailed information about the overdose, including the substance taken, the amount, and the time it occurred.