Invokamet XR 50mg-500mg 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
Jan 2016
DEA Schedule
Not Controlled
Overview
What is this medicine?
Invokamet XR is a combination medicine used to lower blood sugar in adults with type 2 diabetes. It contains two active ingredients: 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 appears to be the tablet in your stool, but this is a normal occurrence 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 by drinking 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 maintain the effectiveness and safety of your medication, 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 appears to be the tablet in your stool, but this is a normal occurrence 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 by drinking 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 maintain the effectiveness and safety of your medication, 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.
- Monitor your blood sugar levels regularly as instructed.
- Stay well-hydrated to reduce the risk of dehydration and kidney problems.
- Limit or avoid alcohol consumption due to increased risk of lactic acidosis with metformin.
- Practice good hygiene, especially in the genital area, to prevent infections.
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose: Canagliflozin 50 mg/Metformin XR 500 mg orally once daily in the morning with food. Titrate based on efficacy and tolerability. Max dose: Canagliflozin 300 mg/Metformin XR 2000 mg daily.
Dose Range:
50 - 2000 mg
Condition-Specific Dosing:
Type 2 Diabetes Mellitus:
Initial dose: Canagliflozin 50 mg/Metformin XR 500 mg orally once daily. For patients already on metformin, switch to the nearest therapeutically appropriate dose of Invokamet XR. For patients already on canagliflozin, switch to the nearest therapeutically appropriate dose of Invokamet XR. Max daily dose: Canagliflozin 300 mg and Metformin XR 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/1.73m²: No dose adjustment needed. Monitor renal function.
Moderate:
eGFR 45 to <60 mL/min/1.73m²: Initiate with Canagliflozin 50 mg/Metformin XR 500 mg. Max dose Canagliflozin 150 mg/Metformin XR 2000 mg. eGFR 30 to <45 mL/min/1.73m²: Canagliflozin dose should not exceed 100 mg daily. Metformin is not recommended to initiate, and if eGFR falls below 45, assess benefits/risks of continuing metformin. Max dose Canagliflozin 100 mg/Metformin XR 2000 mg (if continued).
Severe:
eGFR <30 mL/min/1.73m²: Contraindicated.
Dialysis:
Contraindicated.
Hepatic Impairment:
Mild:
No dose adjustment for canagliflozin. Metformin: Use with caution.
Moderate:
No dose adjustment for canagliflozin. Metformin: Use with caution.
Severe:
Canagliflozin: No dose adjustment, but clinical experience is limited. Metformin: Contraindicated due to increased risk of lactic acidosis.
Pharmacology
Mechanism of Action
Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor, which reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose (RTG), thereby increasing urinary glucose excretion (UGE). Metformin is a biguanide that 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% (absolute oral bioavailability of a 500 mg metformin tablet given under fasting conditions)
Tmax:
Canagliflozin: 1-2 hours; Metformin XR: 4-8 hours
FoodEffect:
Canagliflozin: No clinically meaningful effect on AUC or Cmax. Metformin XR: Food increases AUC by ~50% and Cmax by ~25% compared to fasting state, but this is not considered clinically significant for efficacy.
Distribution:
Vd:
Canagliflozin: 119 L; Metformin: 654 ± 358 L
ProteinBinding:
Canagliflozin: >99%; Metformin: Negligible
CnssPenetration:
Canagliflozin: Limited; Metformin: Limited
Elimination:
HalfLife:
Canagliflozin: 10.6-13.1 hours; Metformin: Plasma elimination half-life is approximately 6.2 hours, blood half-life is approximately 17.6 hours (due to distribution into red blood cells)
Clearance:
Canagliflozin: Renal clearance is minor; Metformin: Renal clearance is approximately 3.5 times greater than creatinine clearance, indicating tubular secretion.
ExcretionRoute:
Canagliflozin: Fecal (51.5%), Renal (33%); Metformin: Renal (unchanged)
Unchanged:
Canagliflozin: ~33% (renal); Metformin: >90% (renal)
Pharmacodynamics
OnsetOfAction:
Canagliflozin: Within hours (glucose lowering); Metformin: Within days to weeks for full glucose-lowering effect.
PeakEffect:
Canagliflozin: 4-6 hours; Metformin: 2-3 weeks for maximal effect.
DurationOfAction:
Canagliflozin: 24 hours; Metformin: 24 hours (XR formulation).
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 were generally >5 mcg/mL. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years or greater, radiological studies with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. If metformin-associated lactic acidosis is suspected, discontinue Invokamet XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.
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 pass urine 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 pass urine, changes in urine output, blood in the urine, or sudden 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 rare but 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 or between the genitals and rectum, accompanied by fever or feeling unwell.
Increased Risk of Lower Limb Amputations: This medication may increase the risk of amputations, particularly of the toes and feet. Discuss foot care with your doctor, and notify them 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 Possible Side Effects
Most people taking this medication do not experience significant side effects or only have mild ones. However, 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 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 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 pass urine 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 pass urine, changes in urine output, blood in the urine, or sudden 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 rare but 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 or between the genitals and rectum, accompanied by fever or feeling unwell.
Increased Risk of Lower Limb Amputations: This medication may increase the risk of amputations, particularly of the toes and feet. Discuss foot care with your doctor, and notify them 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 Possible Side Effects
Most people taking this medication do not experience significant side effects or only have mild ones. However, 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 possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of lactic acidosis: unusual muscle pain, trouble breathing, stomach discomfort, dizziness, lightheadedness, feeling cold, slow or irregular heartbeat. Seek immediate medical attention.
- Signs of diabetic ketoacidosis (DKA): nausea, vomiting, stomach pain, excessive thirst, frequent urination, unusual sleepiness, fruity breath odor. Seek immediate medical attention.
- Signs of severe dehydration: dizziness, lightheadedness, fainting, especially when standing up.
- Signs of urinary tract infection (UTI): burning sensation when urinating, frequent urination, urgency, pain in the lower abdomen.
- Signs of genital yeast infection (for women): vaginal itching, discharge, odor. (for men): rash or redness on the penis, itching, swelling.
- Signs of Fournier's gangrene: severe pain, tenderness, redness, or swelling in the genital or perineal area, fever, feeling unwell. Seek immediate medical attention.
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:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Acidic blood problems
+ Kidney disease
+ Liver disease
+ Type 1 diabetes
Recent medical events, such as a heart attack or stroke
Any difficulties with eating or drinking, including situations where you may need to fast before a procedure or surgery
Upcoming or recent exams or tests that involve contrast agents (within the past 48 hours)
Additionally, if you are:
Pregnant or think you may be pregnant, note that this medication should not be taken during the second or third trimester
* 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 issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other drugs and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Acidic blood problems
+ Kidney disease
+ Liver disease
+ Type 1 diabetes
Recent medical events, such as a heart attack or stroke
Any difficulties with eating or drinking, including situations where you may need to fast before a procedure or surgery
Upcoming or recent exams or tests that involve contrast agents (within the past 48 hours)
Additionally, if you are:
Pregnant or think you may be pregnant, note that this medication should not be taken during the second or third trimester
* 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 issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other drugs and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
Precautions & Cautions
Important Warnings and Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may advise you to stop taking this drug before certain surgical procedures, and will instruct you on when to resume taking it after the surgery or procedure.
Driving and Blood Sugar Levels
Do not operate a vehicle if your blood sugar levels are low, as this can increase the risk of accidents. To minimize the risk of dizziness or fainting, rise slowly from a sitting or lying position, and exercise caution when climbing stairs.
Diet, Exercise, and Lifestyle
Follow 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 ensure safe management of your condition. Regularly check your blood sugar levels and have your blood work and other lab tests done as directed by your doctor. Discuss with your doctor the most suitable glucose tests for your needs.
Interactions and Lab Tests
This medication may affect certain lab tests, so inform all your healthcare providers and lab personnel that you are taking this drug. Additionally, consult with your doctor before consuming alcohol.
Potential Side Effects
High cholesterol has been reported in some individuals taking this medication. If you have concerns, discuss them with your doctor. Be cautious in hot weather or during physical activity, and drink plenty of fluids to prevent dehydration. If you experience vomiting, diarrhea, or are unable to drink fluids, contact your doctor to avoid dehydration, which can lead to low blood pressure or worsen kidney problems.
Blood Sugar Control
Stressful events, such as fever, infection, injury, or surgery, can make it more challenging to control blood sugar levels. Changes in physical activity, exercise, or diet can also impact blood sugar management.
Vitamin B-12 Levels
Long-term treatment with metformin may lead to low vitamin B-12 levels. If you have a history of low vitamin B-12 levels, inform your doctor.
Ketoacidosis
This medication can increase the risk of ketoacidosis, a potentially life-threatening condition. This risk is higher in individuals with diabetes, pancreas problems, or those who are sick, dehydrated, or have skipped meals. Check your ketone levels as directed by your doctor, and seek medical attention if you have questions or concerns.
Bone Health and Kidney Problems
This medication may increase the risk of broken bones and kidney problems, including severe urinary tract infections. In some cases, these conditions may require hospitalization or dialysis.
Special Considerations
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 experience a return of fertility while taking this medication. If you wish to avoid pregnancy, use birth control while taking this drug. If you become pregnant or suspect you are pregnant, inform your doctor immediately, as this medication can harm the unborn baby.
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may advise you to stop taking this drug before certain surgical procedures, and will instruct you on when to resume taking it after the surgery or procedure.
Driving and Blood Sugar Levels
Do not operate a vehicle if your blood sugar levels are low, as this can increase the risk of accidents. To minimize the risk of dizziness or fainting, rise slowly from a sitting or lying position, and exercise caution when climbing stairs.
Diet, Exercise, and Lifestyle
Follow 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 ensure safe management of your condition. Regularly check your blood sugar levels and have your blood work and other lab tests done as directed by your doctor. Discuss with your doctor the most suitable glucose tests for your needs.
Interactions and Lab Tests
This medication may affect certain lab tests, so inform all your healthcare providers and lab personnel that you are taking this drug. Additionally, consult with your doctor before consuming alcohol.
Potential Side Effects
High cholesterol has been reported in some individuals taking this medication. If you have concerns, discuss them with your doctor. Be cautious in hot weather or during physical activity, and drink plenty of fluids to prevent dehydration. If you experience vomiting, diarrhea, or are unable to drink fluids, contact your doctor to avoid dehydration, which can lead to low blood pressure or worsen kidney problems.
Blood Sugar Control
Stressful events, such as fever, infection, injury, or surgery, can make it more challenging to control blood sugar levels. Changes in physical activity, exercise, or diet can also impact blood sugar management.
Vitamin B-12 Levels
Long-term treatment with metformin may lead to low vitamin B-12 levels. If you have a history of low vitamin B-12 levels, inform your doctor.
Ketoacidosis
This medication can increase the risk of ketoacidosis, a potentially life-threatening condition. This risk is higher in individuals with diabetes, pancreas problems, or those who are sick, dehydrated, or have skipped meals. Check your ketone levels as directed by your doctor, and seek medical attention if you have questions or concerns.
Bone Health and Kidney Problems
This medication may increase the risk of broken bones and kidney problems, including severe urinary tract infections. In some cases, these conditions may require hospitalization or dialysis.
Special Considerations
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 experience a return of fertility while taking this medication. If you wish to avoid pregnancy, use birth control while taking this drug. If you become pregnant or suspect you are pregnant, inform your doctor immediately, as this medication can harm the unborn baby.
Overdose Information
Overdose Symptoms:
- Hypoglycemia (if taken with insulin or sulfonylureas)
- Lactic acidosis (severe and potentially fatal)
- Volume depletion/dehydration
- Electrolyte imbalances
What to Do:
Call 1-800-222-1222 (Poison Control). Seek immediate medical attention. Treatment is supportive and symptomatic. Hemodialysis may be useful for metformin overdose.
Drug Interactions
Contraindicated Interactions
Major Interactions
- Rifampin (decreases canagliflozin exposure, consider increasing canagliflozin dose)
- 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 canagliflozin or metformin)
- Carbonic Anhydrase Inhibitors (e.g., topiramate, acetazolamide, increased risk of lactic acidosis with metformin)
- Drugs that reduce metformin clearance (e.g., cimetidine, ranolazine, dolutegravir, isavuconazonium, trimethoprim, verapamil, increased risk of lactic acidosis)
Moderate Interactions
- Digoxin (canagliflozin may increase digoxin exposure, monitor digoxin levels)
- Phenytoin (canagliflozin may decrease phenytoin exposure, monitor phenytoin levels)
- Lithium (SGLT2 inhibitors may decrease lithium levels, monitor lithium levels)
- Corticosteroids (may increase blood glucose, requiring metformin dose adjustment)
Minor Interactions
- Not specifically listed as minor for this combination, but general caution with drugs affecting glucose levels.
Monitoring
Baseline Monitoring
Renal Function (eGFR)
Rationale: To assess eligibility for treatment and establish baseline for dose adjustments and contraindications.
Timing: Prior to initiation
Glycated Hemoglobin (HbA1c)
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation
Blood Glucose (Fasting and Postprandial)
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation
Electrolytes (especially bicarbonate)
Rationale: To assess for baseline metabolic acidosis risk, particularly for metformin.
Timing: Prior to initiation
Liver Function Tests (LFTs)
Rationale: To assess for baseline hepatic impairment, particularly for metformin contraindication.
Timing: Prior to initiation
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: >60 mL/min/1.73m² for full dose; adjust or discontinue based on guidelines.
Action Threshold: eGFR <60 mL/min/1.73m² requires dose adjustment; eGFR <30 mL/min/1.73m² requires discontinuation.
Glycated Hemoglobin (HbA1c)
Frequency: Every 3-6 months.
Target: Individualized, typically <7%.
Action Threshold: Above target range may indicate need for dose titration 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.
Signs and Symptoms of Lactic Acidosis
Frequency: Continuously, patient education is key.
Target: N/A
Action Threshold: Any suspicion (e.g., malaise, myalgia, respiratory distress, abdominal pain) requires immediate medical attention and drug discontinuation.
Signs and Symptoms of Urinary Tract Infections (UTIs) and Genital Mycotic Infections
Frequency: Continuously, patient education is key.
Target: N/A
Action Threshold: Any suspicion requires medical evaluation and treatment.
Volume Status/Blood Pressure
Frequency: Regularly, especially in patients prone to hypotension.
Target: Normotensive.
Action Threshold: Symptomatic hypotension or signs of dehydration.
Symptom Monitoring
- Symptoms of lactic acidosis (unusual muscle pain, trouble breathing, stomach discomfort, dizziness, lightheadedness, feeling cold)
- Symptoms of hypoglycemia (shakiness, sweating, confusion, hunger, irritability)
- Symptoms of urinary tract infection (burning urination, frequent urination, urgency, pain in lower abdomen)
- Symptoms of genital mycotic infection (itching, redness, discharge, rash in genital area)
- Symptoms of dehydration/volume depletion (dizziness, lightheadedness, fainting, dry mouth, excessive thirst)
- Symptoms of diabetic ketoacidosis (nausea, vomiting, abdominal pain, excessive thirst, rapid deep breathing, unusual sleepiness, fruity breath odor)
- Symptoms of Fournier's gangrene (pain, tenderness, redness, or swelling in the genital or perineal area, fever, malaise)
Special Patient Groups
Pregnancy
Generally not recommended during the second and third trimesters due to potential adverse renal effects on the developing fetus (canagliflozin). Metformin is often continued during pregnancy if benefits outweigh risks, but Invokamet XR is a combination product. Discuss with healthcare provider.
Trimester-Specific Risks:
First Trimester:
Limited data for canagliflozin. Metformin generally considered low risk.
Second Trimester:
Canagliflozin: Potential for adverse renal effects on the developing fetus (due to SGLT2 inhibition).
Third Trimester:
Canagliflozin: Potential for adverse renal effects on the developing fetus (due to SGLT2 inhibition).
Lactation
Not recommended. Metformin is excreted into human milk. It is unknown if canagliflozin is excreted into human milk. Due to the potential for serious adverse reactions in a breastfed infant, advise women not to breastfeed while taking Invokamet XR.
Infant Risk:
Risk of lactic acidosis (metformin), unknown risk for canagliflozin.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients under 18 years of age.
Geriatric Use
Increased risk of volume depletion, hypotension, and renal impairment. More frequent monitoring of renal function is recommended. Metformin dose should be carefully titrated based on renal function.
Clinical Information
Clinical Pearls
- Invokamet XR should be taken once daily in the morning with food to reduce gastrointestinal side effects of metformin.
- Ensure adequate hydration, especially during periods of illness, hot weather, or strenuous exercise, to minimize the risk of volume depletion and acute kidney injury.
- Educate patients on the signs and symptoms of lactic acidosis, DKA, UTIs, genital mycotic infections, and Fournier's gangrene, and advise them to seek immediate medical attention if these occur.
- Temporarily discontinue Invokamet XR before radiological procedures involving iodinated contrast media, surgery, or other procedures requiring restricted food and fluid intake.
- Regularly monitor renal function (eGFR) due to dose adjustments and contraindications for both components based on kidney function.
- Consider the risk of lower limb amputation with canagliflozin, especially in patients with pre-existing cardiovascular disease or risk factors for amputation.
Alternative Therapies
- Other SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin, ertugliflozin)
- Other biguanides (metformin monotherapy)
- DPP-4 inhibitors (e.g., sitagliptin, saxagliptin, linagliptin)
- GLP-1 receptor agonists (e.g., liraglutide, semaglutide, dulaglutide)
- Sulfonylureas (e.g., glipizide, glyburide, glimepiride)
- Thiazolidinediones (e.g., pioglitazone, rosiglitazone)
- Insulin
Cost & Coverage
Average Cost:
Varies widely, typically $500-$700+ 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's essential to contact your doctor for further guidance. 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 provides crucial information about its use. Please read this guide carefully and review it again whenever you receive a refill of your medication. If you have any questions or concerns about this medication, don't 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 details about the medication taken, the amount consumed, and the time it occurred.
This medication is accompanied by a Medication Guide, which provides crucial information about its use. Please read this guide carefully and review it again whenever you receive a refill of your medication. If you have any questions or concerns about this medication, don't 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 details about the medication taken, the amount consumed, and the time it occurred.