Invokamet XR 50-1000 Tablets
WARNING: Rarely, metformin may cause too much lactic acid in the blood (lactic acidosis). The risk is higher in people who have kidney problems, liver problems, heart failure, use alcohol, or take certain other drugs, including topiramate. The risk is also higher in people who are 65 or older and in people who are having surgery, an exam or test with contrast, or other procedures. If lactic acidosis happens, it can lead to other health problems and can be deadly. Kidney tests may be done while taking this drug.Do not take this drug if you have a very bad infection, low oxygen, or a lot of fluid loss (dehydration).Call your doctor right away if you have signs of too much lactic acid in the blood (lactic acidosis) like confusion; fast breathing; fast or slow heartbeat; a heartbeat that does not feel normal; very bad stomach pain, upset stomach, or throwing up; feeling very sleepy; shortness of breath; feeling very tired or weak; very bad dizziness; feeling cold; or muscle pain or cramps. @ COMMON USES: It is used to help control blood sugar in people with type 2 diabetes.It is used to lower the chance of heart attack, stroke, new or worse kidney problems, having to go to the hospital for heart failure, and death in some people.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Antidiabetic, Oral
Pharmacologic Class
Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitor; Biguanide
Pregnancy Category
Not available
FDA Approved
Aug 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Invokamet XR is a medication used to help manage blood sugar levels in adults with type 2 diabetes. It contains two medicines: canagliflozin, which helps your kidneys remove more sugar from your body through urine, and metformin, which helps your body use insulin better and reduces the amount of sugar your liver makes.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. Take your medication with breakfast to help your body absorb it properly. Swallow the tablet whole - do not chew, break, or crush it. You may notice what looks like the tablet in your stool after taking it, but this is completely normal and not a cause for concern. If you have any questions or concerns, be sure to discuss them with your doctor.
It's also important to stay hydrated while taking this medication, so drink plenty of non-caffeinated liquids unless your doctor advises you to limit your fluid intake. Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
To keep your medication effective and safe, store it in its original container at room temperature in a dry place. Avoid storing it in a bathroom. If you need to store your medication outside of its original container, be sure to discard any unused portion after 30 days.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for a missed one.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. Take your medication with breakfast to help your body absorb it properly. Swallow the tablet whole - do not chew, break, or crush it. You may notice what looks like the tablet in your stool after taking it, but this is completely normal and not a cause for concern. If you have any questions or concerns, be sure to discuss them with your doctor.
It's also important to stay hydrated while taking this medication, so drink plenty of non-caffeinated liquids unless your doctor advises you to limit your fluid intake. Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
To keep your medication effective and safe, store it in its original container at room temperature in a dry place. Avoid storing it in a bathroom. If you need to store your medication outside of its original container, be sure to discard any unused portion after 30 days.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for 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.
- Stay well-hydrated, especially when exercising or in hot weather, to reduce the risk of dehydration and kidney problems.
- Limit alcohol intake, as it can increase the risk of lactic acidosis with metformin.
- Monitor your blood sugar levels regularly as instructed by your doctor.
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: Canagliflozin 50 mg/Metformin XR 500 mg or 50 mg/1000 mg orally once daily in the morning with food. Titrate based on efficacy and tolerability.
Dose Range:
50 - 300 mg
Condition-Specific Dosing:
Maximum Dose:
Canagliflozin 300 mg/Metformin XR 2000 mg orally once daily.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
eGFR 60 mL/min/1.73m2 or greater: No dose adjustment needed. eGFR 45 to less than 60 mL/min/1.73m2: Max canagliflozin 100 mg/day, max metformin XR 1000 mg/day.
Moderate:
eGFR 30 to less than 45 mL/min/1.73m2: Contraindicated for canagliflozin for glycemic control. Metformin XR dose should not exceed 1000 mg/day, and initiation is not recommended. If already on metformin, assess benefits/risks.
Severe:
eGFR less than 30 mL/min/1.73m2: Contraindicated (due to metformin component).
Dialysis:
Contraindicated (due to metformin component).
Hepatic Impairment:
Mild:
No dose adjustment for canagliflozin. Metformin: Use with caution.
Moderate:
No dose adjustment for canagliflozin. Metformin: Use with caution.
Severe:
Contraindicated (due to metformin component).
Pharmacology
Mechanism of Action
Invokamet XR combines two antihyperglycemic agents with different mechanisms of action: Canagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, and Metformin, a biguanide. Canagliflozin reduces renal glucose reabsorption and lowers the renal threshold for glucose (RTG), leading to increased urinary glucose excretion. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Pharmacokinetics
Absorption:
Bioavailability:
Canagliflozin: ~65%; Metformin: ~50-60% (oral, ER formulation has slower absorption)
Tmax:
Canagliflozin: 1-2 hours; Metformin XR: 4-8 hours
FoodEffect:
Canagliflozin: Food delays Tmax and reduces Cmax. Metformin XR: Food slightly decreases Cmax and increases Tmax, but overall absorption is similar.
Distribution:
Vd:
Canagliflozin: ~119 L; Metformin: ~654 L
ProteinBinding:
Canagliflozin: >99%; Metformin: Negligible
CnssPenetration:
Canagliflozin: Limited; Metformin: Limited
Elimination:
HalfLife:
Canagliflozin: ~10.6-13.1 hours; Metformin: ~6.2 hours (plasma), ~17.6 hours (blood)
Clearance:
Canagliflozin: Renal and fecal; Metformin: Renal
ExcretionRoute:
Canagliflozin: Renal (approx. 33% as unchanged drug and metabolites), Fecal (approx. 60%); Metformin: Renal (primarily as unchanged drug)
Unchanged:
Canagliflozin: ~33% (renal); Metformin: >90% (renal)
Pharmacodynamics
OnsetOfAction:
Canagliflozin: Within hours; Metformin: Within days to weeks for full effect
PeakEffect:
Canagliflozin: Peak glucose lowering within hours; Metformin: Peak glucose lowering within 2-3 weeks
DurationOfAction:
Canagliflozin: 24 hours; Metformin XR: 24 hours
Safety & Warnings
BLACK BOX WARNING
Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate/pyruvate ratio; metformin plasma levels generally >5 mcg/mL. If metformin-associated lactic acidosis is suspected, discontinue Invokamet XR and institute general supportive measures promptly in a hospital setting. Prompt hemodialysis is recommended. Educate patients and clinicians on risk factors and symptoms of lactic acidosis. Instruct patients to discontinue Invokamet XR and seek immediate medical attention if symptoms occur. Risk factors include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors), age 65 years old or greater, radiological studies with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Fluid and Electrolyte Problems: Mood changes, confusion, muscle pain or weakness, fast or abnormal heartbeat, severe dizziness or fainting, increased thirst, seizures, feeling extremely tired or weak, decreased appetite, inability to urinate or changes in urine output, dry mouth, dry eyes, or severe stomach upset or vomiting.
Urinary Tract Infection (UTI): Blood in the urine, burning or pain while urinating, frequent or urgent need to urinate, fever, lower abdominal pain, or pelvic pain.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or significant weight gain.
Vaginal Yeast Infection: Itching, unpleasant odor, or discharge. Report these symptoms to your doctor.
Yeast Infection of the Penis: Pain, swelling, rash, or discharge. Report these symptoms to your doctor.
Bone Pain: Notify your doctor if you experience bone pain.
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, or 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 certain fruit juices.
Stomach Problems: While stomach upset, vomiting, or diarrhea are common when starting this medication, if you experience these symptoms later during treatment, contact your doctor right away, as they may be a sign of a serious condition called lactic acidosis.
Rare but Serious Infection: A potentially life-threatening infection has been reported with medications like this one. Seek medical help immediately if you experience tenderness, redness, or swelling in the genital area, along with fever or general feeling of illness.
Increased Risk of Lower Limb Amputations: This medication may increase the risk of toe and foot amputations. To minimize this risk, discuss foot care with your doctor, especially if you have a history of amputation, blood vessel disease, nerve disease, or foot ulcers due to diabetes. Contact your doctor right away if you experience new pain or tenderness, sores or ulcers, or infections in your legs or feet.
Other Side Effects
Most people taking this medication do not experience significant side effects, but some may occur. If you are bothered by any of the following side effects or if they persist, contact your doctor:
Frequent urination
Gas
Stomach pain or heartburn
Diarrhea, upset stomach, or vomiting
Headache
* Feeling tired or weak
This is not an exhaustive list of potential side effects. If you have 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 immediately or seek emergency medical attention:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Fluid and Electrolyte Problems: Mood changes, confusion, muscle pain or weakness, fast or abnormal heartbeat, severe dizziness or fainting, increased thirst, seizures, feeling extremely tired or weak, decreased appetite, inability to urinate or changes in urine output, dry mouth, dry eyes, or severe stomach upset or vomiting.
Urinary Tract Infection (UTI): Blood in the urine, burning or pain while urinating, frequent or urgent need to urinate, fever, lower abdominal pain, or pelvic pain.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or significant weight gain.
Vaginal Yeast Infection: Itching, unpleasant odor, or discharge. Report these symptoms to your doctor.
Yeast Infection of the Penis: Pain, swelling, rash, or discharge. Report these symptoms to your doctor.
Bone Pain: Notify your doctor if you experience bone pain.
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, or 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 certain fruit juices.
Stomach Problems: While stomach upset, vomiting, or diarrhea are common when starting this medication, if you experience these symptoms later during treatment, contact your doctor right away, as they may be a sign of a serious condition called lactic acidosis.
Rare but Serious Infection: A potentially life-threatening infection has been reported with medications like this one. Seek medical help immediately if you experience tenderness, redness, or swelling in the genital area, along with fever or general feeling of illness.
Increased Risk of Lower Limb Amputations: This medication may increase the risk of toe and foot amputations. To minimize this risk, discuss foot care with your doctor, especially if you have a history of amputation, blood vessel disease, nerve disease, or foot ulcers due to diabetes. Contact your doctor right away if you experience new pain or tenderness, sores or ulcers, or infections in your legs or feet.
Other Side Effects
Most people taking this medication do not experience significant side effects, but some may occur. If you are bothered by any of the following side effects or if they persist, contact your doctor:
Frequent urination
Gas
Stomach pain or heartburn
Diarrhea, upset stomach, or vomiting
Headache
* Feeling tired or weak
This is not an exhaustive list of potential side effects. If you have concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of lactic acidosis: unusual muscle pain, trouble breathing, stomach discomfort, dizziness, lightheadedness, feeling cold, or a slow/irregular heartbeat. Seek immediate medical attention.
- Signs of dehydration: dizziness, lightheadedness, feeling faint, especially when standing up.
- Signs of urinary tract infection: burning sensation when urinating, frequent urination, urgent need to urinate, pain in the lower abdomen or back, fever.
- Signs of genital yeast infection: itching or irritation in the genital area, discharge, or odor.
- Signs of diabetic ketoacidosis (DKA): nausea, vomiting, stomach pain, excessive thirst, rapid deep breathing, unusual sleepiness, or a fruity smell to your breath. Seek immediate medical attention.
- Signs of hypoglycemia (low blood sugar): sweating, shaking, fast heartbeat, hunger, confusion, dizziness, or blurred vision. Carry a source of sugar (e.g., glucose tablets, fruit juice) to treat mild hypoglycemia.
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. Be sure to describe the allergic reactions you have experienced.
Certain health conditions, such as:
+ Acidic blood problems
+ Kidney disease
+ Liver disease
+ Type 1 diabetes
Recent heart attack or stroke
Inability to eat or drink normally, including situations before procedures or surgery
Upcoming or recent exams or tests using contrast media (within the past 48 hours)
Additionally, inform your doctor if you are:
Pregnant or think you might be pregnant. Do not take this medication during the second or third trimester of pregnancy.
* Breastfeeding. You should not breastfeed 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 change the dose 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. Be sure to describe the allergic reactions you have experienced.
Certain health conditions, such as:
+ Acidic blood problems
+ Kidney disease
+ Liver disease
+ Type 1 diabetes
Recent heart attack or stroke
Inability to eat or drink normally, including situations before procedures or surgery
Upcoming or recent exams or tests using contrast media (within the past 48 hours)
Additionally, inform your doctor if you are:
Pregnant or think you might be pregnant. Do not take this medication during the second or third trimester of pregnancy.
* Breastfeeding. You should not breastfeed 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 change the dose of any medication without consulting your doctor first.
Precautions & 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 advise you to stop taking this drug before certain surgical procedures, and if so, they will instruct you on when to resume taking it after the surgery or procedure.
To ensure your safety, avoid driving if you have experienced low blood sugar, as it increases the risk of accidents. To minimize the risk of dizziness or fainting, get up slowly from a sitting or lying down position, and be cautious when climbing stairs. Adhere to the diet and exercise plan recommended by your doctor.
If you are on a low-salt or salt-free diet, consult with your doctor to discuss any necessary adjustments. Regularly check your blood work and other lab tests as directed by your doctor, and monitor your blood sugar levels as instructed. Your doctor can recommend the most suitable glucose tests for you to use.
Be aware that this medication may affect certain lab tests, so inform all your healthcare providers and lab personnel that you are taking this drug. Before consuming alcohol, discuss the potential risks with your doctor.
There is a risk of developing high cholesterol while taking this medication. If you have concerns, consult with your doctor. In hot weather or during physical activity, drink plenty of fluids to prevent dehydration. If you are unable to consume liquids orally 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.
During periods of stress, such as fever, infection, injury, or surgery, it may be more challenging to control your blood sugar levels. Changes in physical activity, exercise, or diet can also impact your blood sugar levels.
Long-term treatment with metformin may cause a decrease in vitamin B-12 levels. If you have a history of low vitamin B-12 levels, discuss this with your doctor.
A rare but serious condition called ketoacidosis (too much acid in the blood or urine) can occur while taking this medication. This condition may require hospitalization and can be life-threatening, even if your blood sugar levels are below 250. People with diabetes, pancreas problems, or those who are sick, dehydrated, or have skipped 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 directed by your doctor, and consult with them if you have any questions.
This medication may increase the risk of bone fractures. Discuss this potential risk with your doctor. Kidney problems and severe urinary tract infections (UTIs) have been reported, and in some cases, hospitalization may be necessary. Kidney problems may require dialysis.
If you are 65 years 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 experience a return of fertility while taking this medication. To avoid pregnancy, use birth control while taking this drug.
If you are pregnant or become pregnant while taking this medication, contact your doctor immediately, as it may harm the unborn baby.
To ensure your safety, avoid driving if you have experienced low blood sugar, as it increases the risk of accidents. To minimize the risk of dizziness or fainting, get up slowly from a sitting or lying down position, and be cautious when climbing stairs. Adhere to the diet and exercise plan recommended by your doctor.
If you are on a low-salt or salt-free diet, consult with your doctor to discuss any necessary adjustments. Regularly check your blood work and other lab tests as directed by your doctor, and monitor your blood sugar levels as instructed. Your doctor can recommend the most suitable glucose tests for you to use.
Be aware that this medication may affect certain lab tests, so inform all your healthcare providers and lab personnel that you are taking this drug. Before consuming alcohol, discuss the potential risks with your doctor.
There is a risk of developing high cholesterol while taking this medication. If you have concerns, consult with your doctor. In hot weather or during physical activity, drink plenty of fluids to prevent dehydration. If you are unable to consume liquids orally 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.
During periods of stress, such as fever, infection, injury, or surgery, it may be more challenging to control your blood sugar levels. Changes in physical activity, exercise, or diet can also impact your blood sugar levels.
Long-term treatment with metformin may cause a decrease in vitamin B-12 levels. If you have a history of low vitamin B-12 levels, discuss this with your doctor.
A rare but serious condition called ketoacidosis (too much acid in the blood or urine) can occur while taking this medication. This condition may require hospitalization and can be life-threatening, even if your blood sugar levels are below 250. People with diabetes, pancreas problems, or those who are sick, dehydrated, or have skipped 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 directed by your doctor, and consult with them if you have any questions.
This medication may increase the risk of bone fractures. Discuss this potential risk with your doctor. Kidney problems and severe urinary tract infections (UTIs) have been reported, and in some cases, hospitalization may be necessary. Kidney problems may require dialysis.
If you are 65 years 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 experience a return of fertility while taking this medication. To avoid pregnancy, use birth control while taking this drug.
If you are pregnant or become pregnant while taking this medication, contact your doctor immediately, as it may harm the unborn baby.
Overdose Information
Overdose Symptoms:
- Lactic acidosis (severe)
- Hypoglycemia (if co-administered with insulin/sulfonylureas)
- Severe dehydration
- Renal failure
What to Do:
Seek immediate medical attention or call a poison control center. In the US, call 1-800-222-1222. Treatment is supportive and may include hemodialysis for metformin overdose.
Drug Interactions
Contraindicated Interactions
- Iodinated contrast media (for metformin, temporarily discontinue)
- Severe renal impairment (eGFR <30 mL/min/1.73m2)
Major Interactions
- Alcohol (increased risk of lactic acidosis with metformin)
- Carbonic anhydrase inhibitors (e.g., topiramate, acetazolamide, zonisamide, dichlorphenamide - increased risk of lactic acidosis with metformin)
- UGT enzyme inducers (e.g., rifampin, phenytoin, phenobarbital, ritonavir - may decrease canagliflozin exposure)
- Diuretics (loop or thiazide - increased risk of volume depletion and hypotension with canagliflozin)
- Insulin and insulin secretagogues (e.g., sulfonylureas - increased risk of hypoglycemia when co-administered with Invokamet XR)
Moderate Interactions
- Digoxin (canagliflozin may increase digoxin exposure)
- Cimetidine (may increase metformin exposure)
- ACE inhibitors/ARBs (increased risk of hypotension and renal impairment with SGLT2 inhibitors)
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Renal function (eGFR)
Rationale: To determine appropriate dosing and identify contraindications for both canagliflozin and metformin.
Timing: Prior to initiation
HbA1c
Rationale: To assess baseline glycemic control.
Timing: Prior to initiation
Blood glucose (fasting and postprandial)
Rationale: To assess baseline glycemic control.
Timing: Prior to initiation
Vitamin B12 levels
Rationale: Metformin can decrease Vitamin B12 levels.
Timing: Prior to initiation (consider, especially in at-risk patients)
Routine Monitoring
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: Daily or as directed by healthcare provider
Target: Individualized, e.g., fasting 80-130 mg/dL, postprandial <180 mg/dL
Action Threshold: Persistent high or low readings require medical evaluation.
Renal function (eGFR)
Frequency: At least annually, more frequently in elderly or those with risk factors for renal impairment
Target: Maintain eGFR >30 mL/min/1.73m2 for continued use of metformin; >45 mL/min/1.73m2 for canagliflozin for glycemic control.
Action Threshold: Dose adjustment or discontinuation if eGFR falls below recommended thresholds.
Signs/symptoms of volume depletion (e.g., dizziness, orthostatic hypotension)
Frequency: Regularly, especially during initiation or with diuretic use
Target: Not applicable
Action Threshold: If symptoms occur, assess hydration status and consider dose adjustment or temporary interruption.
Signs/symptoms of urinary tract infections (UTIs) or genital mycotic infections
Frequency: Regularly
Target: Not applicable
Action Threshold: Prompt evaluation and treatment if symptoms occur.
Vitamin B12 levels
Frequency: Every 2-3 years or if megaloblastic anemia is suspected
Target: Normal range
Action Threshold: Supplementation if levels are low.
Symptom Monitoring
- Symptoms of hypoglycemia (sweating, tremor, confusion, hunger)
- Symptoms of lactic acidosis (unusual muscle pain, difficulty breathing, stomach discomfort, dizziness, lightheadedness, irregular heartbeat, feeling cold)
- Symptoms of dehydration/volume depletion (dizziness, lightheadedness, orthostatic hypotension)
- Symptoms of urinary tract infection (painful urination, frequent urination, urgency, fever)
- Symptoms of genital mycotic infection (itching, discharge, irritation)
- Symptoms of diabetic ketoacidosis (nausea, vomiting, abdominal pain, rapid deep breathing, unusual thirst, fruity breath odor)
Special Patient Groups
Pregnancy
Invokamet XR is not recommended during pregnancy. Poorly controlled diabetes in pregnancy increases the risk of birth defects, perinatal mortality, and other complications. Canagliflozin may cause adverse renal effects in the developing human fetus during the second and third trimesters. Metformin has not been shown to be associated with an increased risk of major birth defects or miscarriage in human studies.
Trimester-Specific Risks:
First Trimester:
Metformin: Limited data suggest no increased risk of major birth defects. Canagliflozin: Limited human data, but animal data suggest potential for renal effects.
Second Trimester:
Canagliflozin: Potential for adverse renal effects (e.g., renal tubular immaturity, hydronephrosis) due to SGLT2 inhibition. Metformin: No known specific risks.
Third Trimester:
Canagliflozin: Potential for adverse renal effects. Metformin: No known specific risks.
Lactation
Invokamet XR is not recommended during breastfeeding. Canagliflozin is present in rat milk, and it is unknown if it is present in human milk. Metformin is excreted into human milk in small amounts. Due to the potential for serious adverse reactions in a breastfed infant (e.g., hypoglycemia, lactic acidosis), a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Canagliflozin: Unknown, but potential for renal effects. Metformin: Low risk, but monitor infant for signs of hypoglycemia or gastrointestinal upset.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients. Not recommended 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 higher risk for volume depletion, hypotension, and lactic acidosis. Renal function should be assessed more frequently. Dose adjustments may be necessary based on eGFR.
Clinical Information
Clinical Pearls
- Always take Invokamet XR in the morning with food to reduce gastrointestinal side effects of metformin and optimize canagliflozin absorption.
- Ensure adequate hydration, especially during illness, hot weather, or strenuous exercise, to minimize the risk of volume depletion and acute kidney injury.
- Discontinue Invokamet XR temporarily before any radiological procedure involving iodinated contrast media or any surgical procedure requiring restricted food/fluid intake.
- Educate patients on the symptoms of lactic acidosis and diabetic ketoacidosis, emphasizing the need for immediate medical attention if these occur.
- Monitor for signs and symptoms of urinary tract infections and genital mycotic infections, which are more common with SGLT2 inhibitors.
- While the initial concern regarding lower limb amputation risk with canagliflozin has been mitigated by newer data, clinicians should still consider patient risk factors for amputation (e.g., history of amputation, peripheral vascular disease, neuropathy, diabetic foot ulcers) and monitor patients carefully.
- Consider periodic Vitamin B12 monitoring due to metformin's potential to lower levels.
Alternative Therapies
- Other SGLT2 inhibitors (e.g., Invokana, Farxiga, Jardiance)
- Other biguanides (e.g., Metformin IR)
- GLP-1 receptor agonists (e.g., Ozempic, Trulicity)
- DPP-4 inhibitors (e.g., Januvia, Tradjenta)
- Sulfonylureas (e.g., Glipizide, Glyburide)
- Thiazolidinediones (e.g., Pioglitazone)
- Insulin
Cost & Coverage
Average Cost:
Varies widely, typically $500-$700+ per 30 tablets
Insurance Coverage:
Tier 2 or 3 (Brand-name drug, often requires prior authorization or step therapy)
General Drug Facts
If your symptoms or health 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, which is a valuable resource that provides important information about its use. It is crucial to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about this medication, do not hesitate to consult 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 reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount consumed, and the time it occurred.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about its use. It is crucial to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about this medication, do not hesitate to consult 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 reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount consumed, and the time it occurred.