Invokamet 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
Pharmacologic Class
Sodium-glucose co-transporter 2 (SGLT2) inhibitor and Biguanide combination
Pregnancy Category
Not available
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 drugs: canagliflozin and metformin. Canagliflozin helps your kidneys remove more sugar from your body through your urine. Metformin helps your body use insulin better, reduces the amount of sugar your liver makes, and decreases the amount of sugar your intestines absorb from food. Together, they help lower your blood sugar levels.
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 meals to help your body absorb it properly. Unless your doctor advises you to limit your fluid intake, drink plenty of non-caffeinated liquids to stay hydrated.
It's essential to continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling better. This will help ensure that your condition is properly managed and prevent any potential complications.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it in its original container at room temperature (between 68°F and 77°F). Keep the container in a dry place, away from direct sunlight and moisture. Avoid storing your medication in a bathroom, as the humidity and temperature fluctuations can affect its potency.
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 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 meals to help your body absorb it properly. Unless your doctor advises you to limit your fluid intake, drink plenty of non-caffeinated liquids to stay hydrated.
It's essential to continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling better. This will help ensure that your condition is properly managed and prevent any potential complications.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it in its original container at room temperature (between 68°F and 77°F). Keep the container in a dry place, away from direct sunlight and moisture. Avoid storing your medication in a bathroom, as the humidity and temperature fluctuations can affect its potency.
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
- Follow a healthy diet 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 alcohol intake, as it can increase the risk of lactic acidosis with metformin.
- Practice good foot care, especially if you have a history of foot problems, due to the potential risk of amputation with canagliflozin.
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: Canagliflozin 50 mg/Metformin 500 mg orally twice daily. Titrate based on efficacy and tolerability.
Dose Range:
500 - 2000 mg
Condition-Specific Dosing:
initialTherapy:
Canagliflozin 50 mg/Metformin 500 mg twice daily. For patients already on metformin, switch to Invokamet with a total daily dose of metformin similar to the current dose and canagliflozin 100 mg or 300 mg.
maximumDose:
Canagliflozin 300 mg/Metformin 2000 mg daily (divided doses).
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
eGFR 60 to <90 mL/min/1.73 m2: No dose adjustment needed for canagliflozin. Metformin dose should be reviewed.
Moderate:
eGFR 45 to <60 mL/min/1.73 m2: Canagliflozin dose limited to 100 mg daily. Metformin maximum dose 1000 mg daily. Monitor renal function every 3-6 months.
Severe:
eGFR <45 mL/min/1.73 m2: Contraindicated (due to metformin).
Dialysis:
Contraindicated (due to metformin).
Hepatic Impairment:
Mild:
No dose adjustment for canagliflozin. Metformin: Use with caution, monitor liver function.
Moderate:
No dose adjustment for canagliflozin. Metformin: Not recommended due to increased risk of lactic acidosis.
Severe:
No dose adjustment for canagliflozin. Metformin: Contraindicated due to increased risk of lactic acidosis.
Pharmacology
Mechanism of Action
Invokamet 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 (UGE) and reduced 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: 65%; Metformin: 50-60% (absolute oral bioavailability)
Tmax:
Canagliflozin: 1-2 hours; Metformin: 2-3 hours
FoodEffect:
Canagliflozin: High-fat meal delays Tmax by 1-2 hours and decreases Cmax by 26%, but does not affect AUC. Can be taken with or without food. Metformin: Food decreases Cmax by 40% and AUC by 25%, and prolongs Tmax. Should be taken with meals to reduce GI side effects.
Distribution:
Vd:
Canagliflozin: 119 L; Metformin: 654 Âą 358 L
ProteinBinding:
Canagliflozin: 99% (primarily to albumin); Metformin: Negligible
CnssPenetration:
Canagliflozin: Limited; Metformin: Limited
Elimination:
HalfLife:
Canagliflozin: 10.6 hours; Metformin: 6.2 hours (plasma), ~17.6 hours (blood)
Clearance:
Canagliflozin: 1.30 L/hr; Metformin: Renal clearance is ~3.5 times greater than creatinine clearance
ExcretionRoute:
Canagliflozin: Feces (approx. 41.5% as unchanged drug, 7.5% as metabolites), Urine (approx. 33% as unchanged drug, 1.5% as metabolites); Metformin: Urine (primarily unchanged drug)
Unchanged:
Canagliflozin: ~33% (urine), ~41.5% (feces); Metformin: >90% (urine)
Pharmacodynamics
OnsetOfAction:
Canagliflozin: Within hours; Metformin: Within days
PeakEffect:
Canagliflozin: 4-6 hours; Metformin: 2-3 weeks for full glycemic effect
DurationOfAction:
Canagliflozin: 24 hours; Metformin: 12-24 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. 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 old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. If lactic acidosis is suspected, discontinue Invokamet and institute general supportive measures promptly 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:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of fluid and electrolyte problems: mood changes, confusion, muscle pain or weakness, 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 nausea and vomiting.
Signs of a 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.
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Vaginal yeast infection: report itching, unpleasant odor, or discharge.
Yeast infection of the penis: report pain, swelling, rash, or discharge.
Bone pain.
Low blood sugar (hypoglycemia) can occur, especially when taking this medication with other diabetes medications. Symptoms may include dizziness, headache, feeling sleepy or weak, shaking, rapid 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.
Common Side Effects
When starting this medication, it's common to experience stomach problems like nausea, vomiting, or diarrhea. However, if you develop stomach problems later during treatment, contact your doctor right away, as this could be a sign of a condition called lactic acidosis.
Rare but Serious Side Effects
A rare but potentially life-threatening infection can occur with medications like this one. Seek medical help immediately if you experience tenderness, redness, or swelling in the genital area or the area between your genitals and rectum, accompanied by fever or feeling unwell.
This medication may increase the risk of lower limb amputations, particularly toe and foot amputations. To minimize this risk, talk to your doctor about proper foot care. If you have a history of amputation, blood vessel disease, nerve disease, or foot ulcers due to diabetes, inform your doctor. Contact your doctor immediately if you experience new pain or tenderness, sores or ulcers, or infections in your legs or feet.
Other Side Effects
Like all medications, this drug can cause side effects, although many people may not experience any or may only have mild side effects. If you're bothered by any of the following side effects or if they persist, contact your doctor:
Frequent urination
Gas
Stomach pain or heartburn
Diarrhea, nausea, 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:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of fluid and electrolyte problems: mood changes, confusion, muscle pain or weakness, 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 nausea and vomiting.
Signs of a 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.
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Vaginal yeast infection: report itching, unpleasant odor, or discharge.
Yeast infection of the penis: report pain, swelling, rash, or discharge.
Bone pain.
Low blood sugar (hypoglycemia) can occur, especially when taking this medication with other diabetes medications. Symptoms may include dizziness, headache, feeling sleepy or weak, shaking, rapid 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.
Common Side Effects
When starting this medication, it's common to experience stomach problems like nausea, vomiting, or diarrhea. However, if you develop stomach problems later during treatment, contact your doctor right away, as this could be a sign of a condition called lactic acidosis.
Rare but Serious Side Effects
A rare but potentially life-threatening infection can occur with medications like this one. Seek medical help immediately if you experience tenderness, redness, or swelling in the genital area or the area between your genitals and rectum, accompanied by fever or feeling unwell.
This medication may increase the risk of lower limb amputations, particularly toe and foot amputations. To minimize this risk, talk to your doctor about proper foot care. If you have a history of amputation, blood vessel disease, nerve disease, or foot ulcers due to diabetes, inform your doctor. Contact your doctor immediately if you experience new pain or tenderness, sores or ulcers, or infections in your legs or feet.
Other Side Effects
Like all medications, this drug can cause side effects, although many people may not experience any or may only have mild side effects. If you're bothered by any of the following side effects or if they persist, contact your doctor:
Frequent urination
Gas
Stomach pain or heartburn
Diarrhea, nausea, 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 low blood sugar (hypoglycemia): sweating, shaking, fast heartbeat, dizziness, hunger, confusion. Carry a source of sugar (e.g., glucose tablets, juice) for emergencies.
- Signs of dehydration/volume depletion: dizziness, lightheadedness, feeling faint, especially when standing up.
- Signs of urinary tract infection (UTI): burning or pain when urinating, frequent urination, cloudy or bloody urine, fever, back pain.
- Signs of genital yeast infection: itching, redness, swelling, rash, or unusual discharge in the genital area.
- Signs of lactic acidosis (a serious side effect of metformin): unusual muscle pain, trouble breathing, unusual stomach discomfort, dizziness, lightheadedness, feeling cold, irregular heartbeat, unusual tiredness or weakness. Seek immediate medical attention.
- Signs of diabetic ketoacidosis (DKA): nausea, vomiting, stomach pain, excessive thirst, frequent urination, rapid breathing, fruity breath odor, confusion, unusual sleepiness. Seek immediate medical attention.
- Signs of Fournier's gangrene (a rare but serious infection): pain, tenderness, redness, or swelling in the genital or perineal area, with fever or 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 conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reactions you have 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, inform your doctor about your pregnancy status or if you are breastfeeding. It is crucial to note that:
This medication should not be taken during the second or third trimester of pregnancy
You should not breastfeed while taking this medication
To ensure your safety, provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter medications you are taking
Natural products and vitamins you are using
Any health problems you have
This information will help your doctor determine if it is safe for you to take this medication with your other medications 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, such as foods or drugs. Describe the allergic reactions you have 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, inform your doctor about your pregnancy status or if you are breastfeeding. It is crucial to note that:
This medication should not be taken during the second or third trimester of pregnancy
You should not breastfeed while taking this medication
To ensure your safety, provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter medications you are taking
Natural products and vitamins you are using
Any health problems you have
This information will help your doctor determine if it is safe for you to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without consulting your doctor first.
Precautions & Cautions
Important Warnings and Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may advise you to stop taking this drug before certain surgical procedures, and will provide guidance 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 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.
Diet, Exercise, and Lab Tests
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 ensure safe management. Regularly check your blood sugar levels and undergo lab tests as directed by your doctor. Be aware that this medication may affect certain lab test results, so inform all healthcare providers and lab personnel that you are taking this drug.
Alcohol Consumption and Cholesterol Levels
Discuss alcohol consumption with your doctor before drinking. High cholesterol has been reported in patients taking this medication; if you have concerns, consult with your doctor.
Hydration and Dehydration
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 consume liquids, contact your doctor to avoid dehydration, which can lead to low blood pressure or worsen kidney problems.
Blood Sugar Control and Stress
Blood sugar control may be more challenging during periods of stress, such as fever, infection, injury, or surgery. Changes in physical activity, exercise, or diet can also impact blood sugar levels.
Vitamin B-12 Levels and Ketoacidosis
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. Ketoacidosis, a condition characterized by excessive acid in the blood or urine, can occur with this medication, even with blood sugar levels below 250. This condition can be life-threatening and may require hospitalization. People with diabetes, pancreas problems, or those who are sick, dehydrated, or skipping meals are at higher risk. Check your ketone levels as directed by your doctor, and consult with your doctor if you have questions.
Bone Health and Kidney Problems
This medication may increase the risk of bone fractures; discuss this with your doctor. Kidney problems and severe urinary tract infections (UTIs) have been reported, and in some cases, may require hospitalization or dialysis.
Age-Related Precautions and Pregnancy
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; use birth control to avoid pregnancy. If you become pregnant or are planning to become pregnant, inform your doctor immediately, as this medication may 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 provide guidance 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 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.
Diet, Exercise, and Lab Tests
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 ensure safe management. Regularly check your blood sugar levels and undergo lab tests as directed by your doctor. Be aware that this medication may affect certain lab test results, so inform all healthcare providers and lab personnel that you are taking this drug.
Alcohol Consumption and Cholesterol Levels
Discuss alcohol consumption with your doctor before drinking. High cholesterol has been reported in patients taking this medication; if you have concerns, consult with your doctor.
Hydration and Dehydration
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 consume liquids, contact your doctor to avoid dehydration, which can lead to low blood pressure or worsen kidney problems.
Blood Sugar Control and Stress
Blood sugar control may be more challenging during periods of stress, such as fever, infection, injury, or surgery. Changes in physical activity, exercise, or diet can also impact blood sugar levels.
Vitamin B-12 Levels and Ketoacidosis
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. Ketoacidosis, a condition characterized by excessive acid in the blood or urine, can occur with this medication, even with blood sugar levels below 250. This condition can be life-threatening and may require hospitalization. People with diabetes, pancreas problems, or those who are sick, dehydrated, or skipping meals are at higher risk. Check your ketone levels as directed by your doctor, and consult with your doctor if you have questions.
Bone Health and Kidney Problems
This medication may increase the risk of bone fractures; discuss this with your doctor. Kidney problems and severe urinary tract infections (UTIs) have been reported, and in some cases, may require hospitalization or dialysis.
Age-Related Precautions and Pregnancy
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; use birth control to avoid pregnancy. If you become pregnant or are planning to become pregnant, inform your doctor immediately, as this medication may harm the unborn baby.
Overdose Information
Overdose Symptoms:
- Hypoglycemia (if taken with insulin or sulfonylureas)
- Lactic acidosis (severe abdominal pain, muscle pain, rapid breathing, coldness, dizziness, irregular heartbeat)
- Volume depletion
- Electrolyte imbalances
What to Do:
Call 911 or Poison Control (1-800-222-1222) immediately. Treatment is supportive and symptomatic. Hemodialysis may be useful for metformin removal.
Drug Interactions
Contraindicated Interactions
- Iodinated contrast agents (for metformin, temporarily discontinue)
- Severe renal impairment (eGFR <45 mL/min/1.73 m2)
- Metabolic acidosis (including diabetic ketoacidosis)
Major Interactions
- Loop diuretics (e.g., furosemide) - increased risk of volume depletion and hypotension
- Insulin and insulin secretagogues (e.g., sulfonylureas) - increased risk of hypoglycemia
- UGT enzyme inducers (e.g., rifampin, phenytoin, phenobarbital) - may decrease canagliflozin exposure
- Drugs that affect renal function or metformin disposition (e.g., NSAIDs, ACE inhibitors, ARBs, cimetidine, ranolazine, dolutegravir, trimethoprim, topiramate, zonisamide) - increased risk of lactic acidosis with metformin
Moderate Interactions
- Digoxin (canagliflozin may increase digoxin exposure)
- Oral contraceptives (canagliflozin may decrease exposure of ethinyl estradiol and levonorgestrel)
- Alcohol (potentiates metformin's effect on lactate metabolism, increasing lactic acidosis risk)
- Corticosteroids, thiazides, other diuretics, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, isoniazid (may produce hyperglycemia, requiring dose adjustment of Invokamet)
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Renal function (eGFR)
Rationale: To determine appropriate dosing and assess contraindications for metformin and canagliflozin.
Timing: Prior to initiation.
Glycated Hemoglobin (HbA1c)
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation.
Blood pressure
Rationale: Canagliflozin can cause orthostatic hypotension.
Timing: Prior to initiation.
Volume status
Rationale: Canagliflozin can cause volume depletion.
Timing: Prior to initiation.
Vitamin B12 levels
Rationale: Metformin can decrease Vitamin B12 levels.
Timing: Consider prior to initiation, especially in patients at risk for deficiency.
Routine Monitoring
Renal function (eGFR)
Frequency: At least annually; more frequently (e.g., every 3-6 months) in patients with eGFR <60 mL/min/1.73 m2 or at risk for renal impairment.
Target: >45 mL/min/1.73 m2 for continued use
Action Threshold: Discontinue if eGFR persistently falls below 45 mL/min/1.73 m2 (for canagliflozin) or 30 mL/min/1.73 m2 (for metformin).
Glycated Hemoglobin (HbA1c)
Frequency: Every 3-6 months.
Target: Individualized, typically <7%
Action Threshold: Adjust dose or add/change therapy if target not met.
Blood glucose (fasting and postprandial)
Frequency: Regularly, as directed by healthcare provider.
Target: Individualized
Action Threshold: Adjust dose or therapy based on readings.
Signs/symptoms of volume depletion (e.g., dizziness, orthostatic hypotension)
Frequency: Regularly, especially during initiation or dose increases.
Target: N/A
Action Threshold: Consider dose reduction, temporary interruption, or fluid intake increase.
Signs/symptoms of lactic acidosis (e.g., malaise, myalgia, respiratory distress, somnolence, abdominal distress)
Frequency: Ongoing vigilance.
Target: N/A
Action Threshold: Discontinue immediately and seek emergency medical attention if suspected.
Vitamin B12 levels
Frequency: Annually or every 2-3 years, especially in patients with peripheral neuropathy or anemia.
Target: Normal range
Action Threshold: Supplement if deficient.
Symptom Monitoring
- Signs of hypoglycemia (sweating, tremor, confusion, hunger)
- Signs of volume depletion (dizziness, lightheadedness, orthostatic hypotension)
- Signs of urinary tract infection (painful urination, frequent urination, urgency, fever)
- Signs of genital mycotic infection (itching, redness, discharge)
- Signs of lactic acidosis (unusual muscle pain, trouble breathing, unusual stomach discomfort, dizziness, lightheadedness, feeling cold, irregular heartbeat)
- Signs of Fournier's gangrene (pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise)
- Signs of diabetic ketoacidosis (nausea, vomiting, abdominal pain, excessive thirst, rapid deep breathing, unusual sleepiness, fruity breath odor)
Special Patient Groups
Pregnancy
Not recommended during pregnancy, especially during the second and third trimesters. Data on canagliflozin use in pregnant women are limited. Metformin crosses the placenta. Poorly controlled diabetes in pregnancy increases maternal and fetal risks. Consider insulin therapy.
Trimester-Specific Risks:
First Trimester:
Limited human data, animal studies show adverse effects at high doses for canagliflozin. Metformin generally considered low risk, but insulin is preferred for glycemic control.
Second Trimester:
Canagliflozin: Not recommended due to potential for adverse renal effects in the developing fetus (due to SGLT2 inhibition affecting fluid and electrolyte homeostasis). Metformin: Continued use may be considered if benefits outweigh risks, but insulin is generally preferred.
Third Trimester:
Canagliflozin: Not recommended due to potential for adverse renal effects in the developing fetus. Metformin: Continued use may be considered if benefits outweigh risks, but insulin is generally preferred.
Lactation
Not recommended during breastfeeding. Canagliflozin is present in rat milk; it is unknown if it is present in human milk. Metformin is excreted into human milk. Due to the potential for serious adverse reactions in a breastfed infant, including lactic acidosis with metformin, and the lack of data for canagliflozin, advise women not to breastfeed while on Invokamet.
Infant Risk:
L3 (Moderate risk) - Potential for lactic acidosis (metformin), unknown for canagliflozin. Monitor for hypoglycemia, GI upset, and growth.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients under 18 years of age.
Geriatric Use
Use with caution, especially in patients âĨ65 years of age, due to increased risk of volume depletion, hypotension, and renal impairment. Metformin's risk of lactic acidosis increases with age and declining renal function. Start with lower doses and titrate slowly. Monitor renal function more frequently.
Clinical Information
Clinical Pearls
- Always assess renal function (eGFR) before initiating and periodically during treatment, as dosing is highly dependent on kidney function, especially for metformin.
- Advise patients to maintain adequate hydration to reduce the risk of volume depletion and acute kidney injury, particularly during illness or hot weather.
- Educate patients on the signs and symptoms of lactic acidosis and diabetic ketoacidosis, emphasizing the need for immediate medical attention if suspected.
- Temporarily discontinue Invokamet before any radiological procedure involving iodinated contrast agents or any surgical procedure requiring restricted food/fluid intake.
- Monitor for signs of urinary tract infections and genital mycotic infections, which are common side effects of SGLT2 inhibitors.
- Counsel patients on good foot care practices due to the historical association of canagliflozin with lower limb amputations, even though the boxed warning has been removed.
- Consider Vitamin B12 supplementation for patients on long-term metformin therapy, especially if they develop symptoms of neuropathy or anemia.
Alternative Therapies
- Other SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin, ertugliflozin)
- Other biguanides (Metformin monotherapy)
- DPP-4 inhibitors (e.g., sitagliptin, saxagliptin)
- GLP-1 receptor agonists (e.g., liraglutide, semaglutide)
- Sulfonylureas (e.g., glipizide, glyburide)
- Thiazolidinediones (e.g., pioglitazone, rosiglitazone)
- Insulin
Cost & Coverage
Average Cost:
$500 - $700 per 30 tablets (approximate for 50/500mg)
Insurance Coverage:
Tier 2 or 3 (Brand name)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure your safety, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which provides crucial information. Please read this guide carefully and review it again whenever you receive a refill. If you have any questions or concerns about this medication, we encourage you to discuss them with your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.