Invokamet 50mg/1000mg 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, combination
Pharmacologic Class
Sodium-glucose co-transporter 2 (SGLT2) inhibitor; Biguanide
Pregnancy Category
Category D (Canagliflozin in 2nd/3rd trimester)
FDA Approved
Aug 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Invokamet is a combination medicine used to treat type 2 diabetes. It contains two active ingredients: canagliflozin and metformin. Canagliflozin works by helping your kidneys remove more sugar from your body through your urine. Metformin works by reducing the amount of sugar your liver makes, decreasing sugar absorption from your gut, and improving how your body uses insulin. Together, they help lower your blood sugar levels.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication with meals as directed. It's also important to drink plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better. This will help ensure that you receive the full benefits of the treatment.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it in its original container at room temperature. Keep it in a dry place, away from the 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 the missed one.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication with meals as directed. It's also important to drink plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better. This will help ensure that you receive the full benefits of the treatment.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it in its original container at room temperature. Keep it in a dry place, away from the 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 the missed one.
Lifestyle & Tips
- Take Invokamet exactly as prescribed by your doctor, usually twice a day with meals to reduce stomach upset from metformin.
- Maintain a healthy diet as recommended by your doctor or dietitian.
- Engage in regular physical activity as advised by your healthcare provider.
- Stay well-hydrated by drinking plenty of fluids, especially when exercising or in hot weather, to reduce the risk of dehydration and kidney problems.
- Monitor your blood sugar levels regularly as instructed by your doctor.
- Carry a source of sugar (e.g., glucose tablets, hard candy) to treat mild hypoglycemia if you are also taking insulin or a sulfonylurea.
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: Canagliflozin 50 mg/Metformin 500 mg twice daily or Canagliflozin 50 mg/Metformin 1000 mg once daily. Max: Canagliflozin 300 mg/day, Metformin 2000 mg/day.
Dose Range:
50 - 300 mg
Condition-Specific Dosing:
prior_canagliflozin_therapy:
Patients already on canagliflozin 100 mg may start with Invokamet 100 mg/Metformin 500 mg or 1000 mg twice daily. Patients on canagliflozin 300 mg may start with Invokamet 150 mg/Metformin 500 mg or 1000 mg twice daily.
prior_metformin_therapy:
Patients already on metformin may switch to Invokamet with a total daily dose of metformin similar to their previous dose, and canagliflozin 50 mg or 100 mg once daily.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
eGFR 45 to <60 mL/min/1.73 m2: Canagliflozin dose limited to 100 mg once daily. Metformin dose should be reviewed and potentially reduced.
Moderate:
eGFR 30 to <45 mL/min/1.73 m2: Contraindicated for canagliflozin. Metformin is also contraindicated.
Severe:
eGFR <30 mL/min/1.73 m2: Contraindicated for Invokamet.
Dialysis:
Contraindicated for Invokamet.
Hepatic Impairment:
Mild:
No dose adjustment for canagliflozin. Metformin use should be with caution.
Moderate:
No dose adjustment for canagliflozin. Metformin use should be with caution.
Severe:
Contraindicated due to metformin component (increased risk of lactic acidosis).
Pharmacology
Mechanism of Action
Invokamet combines two antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes mellitus: Canagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, and Metformin, a biguanide.
Canagliflozin: Inhibits SGLT2 in the renal proximal tubules, reducing glucose reabsorption and increasing urinary glucose excretion, thereby lowering plasma glucose concentrations.
Metformin: Decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Canagliflozin: Inhibits SGLT2 in the renal proximal tubules, reducing glucose reabsorption and increasing urinary glucose excretion, thereby lowering plasma glucose concentrations.
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: Approximately 65%; Metformin: 50-60% (absolute oral bioavailability of a 500 mg metformin tablet given under fasting conditions).
Tmax:
Canagliflozin: 1-2 hours; Metformin: 2-3 hours (immediate release).
FoodEffect:
Canagliflozin: Food reduces Cmax but has no significant effect on AUC. Metformin: Food delays absorption and slightly decreases Cmax.
Distribution:
Vd:
Canagliflozin: 83.4 L; Metformin: 654 L.
ProteinBinding:
Canagliflozin: Approximately 99%; Metformin: Negligible.
CnssPenetration:
Canagliflozin: Limited; Metformin: Limited.
Elimination:
HalfLife:
Canagliflozin: 10.6 hours (50 mg) to 13.1 hours (300 mg); Metformin: 6.2 hours (plasma), 17.6 hours (blood).
Clearance:
Canagliflozin: Renal clearance is minor; Metformin: Renal clearance is approximately 3.5 times greater than creatinine clearance, indicating tubular secretion.
ExcretionRoute:
Canagliflozin: Fecal (51.4%) and renal (41.5%); Metformin: Primarily renal (unchanged drug).
Unchanged:
Canagliflozin: Approximately 30-40% in urine; Metformin: >90% in urine.
Pharmacodynamics
OnsetOfAction:
Canagliflozin: Within hours (glucose lowering); Metformin: Within days (full effect over weeks).
PeakEffect:
Canagliflozin: 4-6 hours; Metformin: 2-3 weeks for maximal effect.
DurationOfAction:
Canagliflozin: 24 hours; Metformin: 12-24 hours (immediate release).
Safety & Warnings
BLACK BOX WARNING
Postmarketing cases of lactic acidosis, a serious metabolic complication, have been reported with metformin use and can result in death. The risk of lactic acidosis is increased with renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors), 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 lactic acidosis is suspected, discontinue Invokamet 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 signs or 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 passing out, increased thirst, seizures, feeling very tired or weak, decreased appetite, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or severe upset stomach or vomiting.
Urinary Tract Infection (UTI): Blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
Kidney Problems: Unable to pass urine, change in how much urine is passed, blood in the urine, or a significant weight gain.
Vaginal Yeast Infection: Itching, bad 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 some fruit juices.
Stomach Problems: While stomach problems like upset stomach, 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 your genitals or the area between your genitals and rectum becomes tender, red, or swollen, and you have a fever or do not feel well.
Increased Risk of Lower Limb Amputations: This medication may increase the risk of lower limb amputations, particularly toe and foot amputations. Discuss foot care with your doctor, and notify them if you have a history of amputation, blood vessel disease, nerve disease, or a foot ulcer caused by 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
While not everyone experiences side effects, some people may have mild or moderate side effects. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:
Passing urine more often
Gas
Stomach pain or heartburn
Diarrhea, upset stomach, or vomiting
Headache
* Feeling tired or weak
This is not a comprehensive list of all 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 signs or 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 passing out, increased thirst, seizures, feeling very tired or weak, decreased appetite, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or severe upset stomach or vomiting.
Urinary Tract Infection (UTI): Blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
Kidney Problems: Unable to pass urine, change in how much urine is passed, blood in the urine, or a significant weight gain.
Vaginal Yeast Infection: Itching, bad 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 some fruit juices.
Stomach Problems: While stomach problems like upset stomach, 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 your genitals or the area between your genitals and rectum becomes tender, red, or swollen, and you have a fever or do not feel well.
Increased Risk of Lower Limb Amputations: This medication may increase the risk of lower limb amputations, particularly toe and foot amputations. Discuss foot care with your doctor, and notify them if you have a history of amputation, blood vessel disease, nerve disease, or a foot ulcer caused by 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
While not everyone experiences side effects, some people may have mild or moderate side effects. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:
Passing urine more often
Gas
Stomach pain or heartburn
Diarrhea, upset stomach, or vomiting
Headache
* Feeling tired or weak
This is not a comprehensive list of all 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 (Medical Emergency):** Unusual muscle pain, trouble breathing, stomach pain, dizziness, lightheadedness, feeling cold, very tired or weak. Seek immediate medical attention.
- **Diabetic Ketoacidosis (DKA):** Nausea, vomiting, stomach pain, excessive thirst, rapid deep breathing, unusual sleepiness, fruity breath odor. Seek immediate medical attention.
- **Dehydration/Volume Depletion:** Dizziness, lightheadedness, fainting, especially when standing up.
- **Kidney Problems:** Decreased urination, swelling in your legs or feet.
- **Urinary Tract Infections (UTIs):** Burning sensation when urinating, frequent urination, urgent need to urinate, pain in the lower stomach or pelvis, fever, back pain.
- **Genital Yeast Infections:** Itching, redness, swelling, or discharge in the genital area.
- **Fournier's Gangrene (Rare but Serious):** Pain, tenderness, redness, or swelling in the genital or perineal area, accompanied by fever or malaise. Seek immediate medical attention.
- **Lower Limb Amputation (Rare):** New pain, tenderness, sores, ulcers, or infections in the legs or feet. Report these symptoms to your doctor immediately.
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. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, such as:
+ Acidic blood problems
+ Kidney disease
+ Liver disease
+ Type 1 diabetes
Recent heart attack or stroke
Any difficulties with eating or drinking, including situations where you may be required 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. Do not take this medication during the second or third trimester of pregnancy.
* Breast-feeding. 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 medications and health conditions. Never start, stop, or change the dose 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. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, such as:
+ Acidic blood problems
+ Kidney disease
+ Liver disease
+ Type 1 diabetes
Recent heart attack or stroke
Any difficulties with eating or drinking, including situations where you may be required 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. Do not take this medication during the second or third trimester of pregnancy.
* Breast-feeding. 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 medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
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, rise slowly from a sitting or lying down position, and exercise caution when climbing stairs. Adhere to the diet and exercise plan recommended by your doctor.
If you are following a low-salt or salt-free diet, consult with your doctor to discuss any necessary adjustments. Regularly undergo blood work and other laboratory tests as directed by your doctor, and monitor your blood sugar levels according to their instructions. Your doctor can recommend the most suitable glucose tests for you to use.
Be aware that this medication may affect the results of certain laboratory tests. Inform all your healthcare providers and laboratory personnel that you are taking this drug. Before consuming alcohol, consult with your doctor to discuss any potential risks.
High cholesterol has been associated with this medication. If you have concerns, discuss them 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 on preventing 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 lead to low vitamin B-12 levels. If you have a history of low vitamin B-12 levels, consult with your doctor. A rare but serious condition called ketoacidosis (too much acid in the blood or urine) has been associated with this medication. This condition can be life-threatening and may require hospitalization. People with diabetes or pancreas problems, as well as those who are sick, dehydrated, or have undergone surgery, are at a higher risk of developing ketoacidosis. Additionally, individuals who follow a ketogenic diet, skip meals, or take less than their prescribed insulin dose 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 become pregnant or suspect you may be 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, rise slowly from a sitting or lying down position, and exercise caution when climbing stairs. Adhere to the diet and exercise plan recommended by your doctor.
If you are following a low-salt or salt-free diet, consult with your doctor to discuss any necessary adjustments. Regularly undergo blood work and other laboratory tests as directed by your doctor, and monitor your blood sugar levels according to their instructions. Your doctor can recommend the most suitable glucose tests for you to use.
Be aware that this medication may affect the results of certain laboratory tests. Inform all your healthcare providers and laboratory personnel that you are taking this drug. Before consuming alcohol, consult with your doctor to discuss any potential risks.
High cholesterol has been associated with this medication. If you have concerns, discuss them 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 on preventing 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 lead to low vitamin B-12 levels. If you have a history of low vitamin B-12 levels, consult with your doctor. A rare but serious condition called ketoacidosis (too much acid in the blood or urine) has been associated with this medication. This condition can be life-threatening and may require hospitalization. People with diabetes or pancreas problems, as well as those who are sick, dehydrated, or have undergone surgery, are at a higher risk of developing ketoacidosis. Additionally, individuals who follow a ketogenic diet, skip meals, or take less than their prescribed insulin dose 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 become pregnant or suspect you may be pregnant while taking this medication, contact your doctor immediately, as it may harm the unborn baby.
Overdose Information
Overdose Symptoms:
- Lactic acidosis (severe)
- Severe hypoglycemia (if co-administered with insulin/sulfonylurea)
- Severe dehydration
- Hypotension
- Renal failure
What to Do:
Contact a poison control center or emergency room immediately. Call 1-800-222-1222. Treatment is supportive and symptomatic. Hemodialysis can remove metformin and canagliflozin.
Drug Interactions
Contraindicated Interactions
- Iodinated contrast media (for metformin component - temporarily discontinue Invokamet at the time of or prior to the procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m2, in patients with a history of liver disease, alcoholism, or heart failure, or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the procedure; restart Invokamet if renal function is stable.)
Major Interactions
- Alcohol (increased risk of lactic acidosis with metformin)
- Diuretics (loop or thiazide - increased risk of volume depletion and hypotension with canagliflozin)
- Digoxin (canagliflozin may increase digoxin exposure)
- UGT enzyme inducers (e.g., rifampin, phenytoin, phenobarbital, ritonavir - may decrease canagliflozin exposure)
- Carbonic anhydrase inhibitors (e.g., topiramate, zonisamide, acetazolamide, dichlorphenamide - increased risk of lactic acidosis with metformin)
Moderate Interactions
- Insulin and insulin secretagogues (e.g., sulfonylureas - increased risk of hypoglycemia when co-administered with canagliflozin or metformin)
- Drugs that reduce metformin clearance (e.g., cimetidine, ranolazine, dolutegravir, isavuconazole, trimethoprim, vandetanib - may increase metformin levels)
- Lithium (SGLT2 inhibitors may decrease lithium levels)
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Renal function (eGFR)
Rationale: To assess baseline kidney function and determine appropriate dosing, as both components are renally cleared and contraindicated in severe renal impairment.
Timing: Prior to initiation of therapy.
HbA1c and Fasting Plasma Glucose (FPG)
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation of therapy.
Electrolytes (especially bicarbonate)
Rationale: To assess for baseline acid-base status, relevant for lactic acidosis risk with metformin.
Timing: Prior to initiation of therapy.
Routine Monitoring
Renal function (eGFR)
Frequency: At least annually; more frequently (e.g., 2-4 times per year) in patients with eGFR <60 mL/min/1.73 m2, elderly, or those at risk for renal impairment.
Target: >60 mL/min/1.73 m2 for full dose; >45 mL/min/1.73 m2 for reduced canagliflozin dose; >30 mL/min/1.73 m2 for any use.
Action Threshold: Discontinue if eGFR falls persistently below 45 mL/min/1.73 m2 (canagliflozin) or 30 mL/min/1.73 m2 (metformin).
HbA1c
Frequency: Every 3-6 months.
Target: Individualized, typically <7% for most adults.
Action Threshold: Re-evaluate therapy if target not met.
Blood Glucose (FPG, postprandial)
Frequency: Daily (self-monitoring) or as clinically indicated.
Target: Individualized, e.g., FPG 80-130 mg/dL, postprandial <180 mg/dL.
Action Threshold: Adjust therapy based on trends and patient symptoms.
Signs and symptoms of lactic acidosis
Frequency: Ongoing clinical assessment.
Target: N/A
Action Threshold: Promptly evaluate and discontinue if suspected.
Vitamin B12 levels
Frequency: Periodically (e.g., every 1-2 years) for patients on long-term metformin therapy, especially those with risk factors for deficiency.
Target: Normal range.
Action Threshold: Supplement if deficient.
Symptom Monitoring
- Signs of lactic acidosis (malaise, myalgia, respiratory distress, somnolence, abdominal distress, hypothermia, hypotension)
- Signs of dehydration/volume depletion (dizziness, lightheadedness, orthostatic hypotension)
- Symptoms of urinary tract infection (dysuria, frequent urination, urgency, fever, flank pain)
- Symptoms of genital mycotic infection (itching, discharge, irritation, rash in genital area)
- Symptoms of diabetic ketoacidosis (nausea, vomiting, abdominal pain, excessive thirst, rapid deep breathing, unusual sleepiness)
- Symptoms of hypoglycemia (sweating, tremor, confusion, hunger, irritability, dizziness, rapid heartbeat)
- Symptoms of Fournier's gangrene (tenderness, redness, or swelling in the genital or perineal area, accompanied by fever or malaise)
- New pain, tenderness, sores, ulcers, or infections in the legs or feet (for lower limb amputation risk with canagliflozin)
Special Patient Groups
Pregnancy
Not recommended during the second and third trimesters of pregnancy due to potential adverse renal effects on the developing fetus (canagliflozin). Metformin is generally considered safer in pregnancy for type 2 diabetes or gestational diabetes, but the combination product carries the risk of canagliflozin.
Trimester-Specific Risks:
First Trimester:
Limited human data for canagliflozin. Metformin is often continued for gestational diabetes or PCOS.
Second Trimester:
Canagliflozin: Potential for adverse renal effects (e.g., renal tubular immaturity, hydronephrosis) in the fetus. Not recommended.
Third Trimester:
Canagliflozin: Potential for adverse renal effects (e.g., renal tubular immaturity, hydronephrosis) in the fetus. Not recommended.
Lactation
Not recommended. Both canagliflozin and metformin are excreted into breast milk. Due to the potential for serious adverse reactions in a breastfed infant, 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:
Risk of hypoglycemia, lactic acidosis (metformin), and potential for renal effects (canagliflozin) in the infant.
Pediatric Use
Safety and effectiveness of Invokamet have not been established in pediatric patients. Not recommended for use in patients younger than 18 years of age.
Geriatric Use
Increased risk of renal impairment, volume depletion, and lactic acidosis. Renal function should be assessed more frequently in elderly patients. Exercise caution when prescribing to patients 65 years or older, especially those with eGFR <60 mL/min/1.73 m2.
Clinical Information
Clinical Pearls
- Invokamet should be taken with meals to minimize the gastrointestinal side effects associated with metformin.
- Patients should be educated on the signs and symptoms of lactic acidosis, DKA, UTIs, and genital mycotic infections, and instructed to seek immediate medical attention if these occur.
- Prior to initiation, assess renal function (eGFR) and monitor periodically, as dose adjustments or discontinuation are required based on eGFR.
- Temporarily discontinue Invokamet for procedures requiring iodinated contrast media, surgery, or other conditions that may predispose to hypovolemia, hypotension, or renal impairment.
- Be aware of the increased risk of lower limb amputation with canagliflozin; monitor patients for new pain, tenderness, sores, ulcers, or infections in the legs or feet.
- Consider periodic vitamin B12 level monitoring in patients on long-term metformin therapy, especially those with risk factors for deficiency.
Alternative Therapies
- Other SGLT2 inhibitors (e.g., Invokana, Farxiga, Jardiance)
- Other biguanides (Metformin monotherapy)
- DPP-4 inhibitors (e.g., Januvia, Tradjenta)
- GLP-1 receptor agonists (e.g., Ozempic, Trulicity)
- Sulfonylureas (e.g., Glipizide, Glyburide)
- Thiazolidinediones (e.g., Pioglitazone)
- Insulin
Cost & Coverage
Average Cost:
Varies widely, typically $400-$600+ per 60 tablets (30-day supply)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (preferred or non-preferred brand)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which is a patient fact sheet that provides crucial information. It is vital to read this guide carefully and review it again each time you receive a refill of this medication. If you have any questions or concerns about this medication, 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 seeking help, be prepared to provide details about the overdose, including the substance taken, the amount, and the time it occurred.