8 Invokana Interactions and How to Manage Them

Invokana (canagliflozin) works in a unique way. It’s an oral sodium-glucose co-transporter 2 (SGLT2) inhibitor.

SGLT2 inhibitors such as Invokana help your kidneys remove extra glucose (sugar) through your urine. They also remove excess sodium (salt) by preventing it from being absorbed back into your body. Together, these effects make SGLT2 inhibitors helpful at reducing blood glucose levels and alleviating strain on the heart and kidneys. That’s why Invokana can manage Type 2 diabetes and certain complications from heart disease or kidney disease.

Although Invokana is good at its job, it does have some drug interactions to discuss. Many of them stem from how it works. Here are eight Invokana interactions to keep in mind before starting the medication.

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1. Insulin and sulfonylureas

Other medications that treat diabetes, such as insulin and sulfonylureas (think glipizide and glimepiride), can have an additive effect with Invokana. This means they’re all working to do the same thing — lower blood glucose.

This effect can be too strong if they’re taken together. Combining them can raise the risk of hypoglycemia, which is when your blood glucose falls below 70 mg/dL. Your healthcare provider might suggest lowering the dose of insulin or your sulfonylurea if you’re starting Invokana.

Hypoglycemia is important to recognize and treat. You may experience any of the following symptoms:

• A fast heartbeat

• Shakiness or tremors

• Lightheadedness or weakness

• Irritability

• Sweating

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Having food or drink that contains 15 grams of fast-acting carbohydrates can help treat episodes of low blood sugar. This includes 4 glucose tablets or a half cup of fruit juice.

2. Beta blockers

Metoprolol succinate (Toprol XL), metoprolol tartrate (Lopressor), and atenolol (Tenormin) are all common beta blockers. These are medications that lower heart rate and treat certain heart conditions. They can also treat conditions such as migraines and tremors.

Beta blockers can interact with many diabetes medications, including Invokana. Since they lower heart rate and lessen your “fight or flight” response, they can hide or “mask” certain symptoms of hypoglycemia. This includes fast heart beat, tremors, and irritability. This can be a dangerous interaction because you may not recognize if your glucose is too low. However, beta blockers don’t mask sweating related to hypoglycemia. So this might be a key symptom to look out for.

It’s important to check your blood glucose regularly if you’re taking both Invokana and a beta blocker.

3. Diuretics

Invokana has diuretic effects, similar to other diuretics or “water pills.” It helps your kidneys make more urine. That’s why it could interact with thiazide diuretics, loop diuretics, or potassium-sparing diuretics.

If you take Invokana with a diuretic, there is a higher risk of experiencing dehydration or hypotension (low blood pressure). The highest risk is with loop diuretics, like furosemide (Lasix) or bumetanide (Bumex), which are strong diuretics. Dehydration and hypotension can feel like dizziness, lightheadedness, or weakness.

Check your blood pressure if you develop symptoms like these. If it’s below your target range, it’s a good idea to reach out to your healthcare provider. Your provider may also check your kidney health and hydration levels through a blood test.

4. Anti-seizure medications like phenytoin and phenobarbital

Phenytoin (Dilantin, Phenytek) and phenobarbital treat seizures. They can interact with Invokana by affecting an enzyme (protein) in your body called UDP-glycosyltransferase (shortened to “UGT”).

Normally, UGT helps break down Invokana so your body can clear it from your system. But phenytoin and phenobarbital speed up (induce) UGT’s actions. This can result in your body breaking down Invokana faster than it should, and essentially lowering its effectiveness. In turn, this might make it harder to manage your diabetes or provide enough protection for your kidneys and heart.

If you’re taking either of these seizure medications with Invokana, your healthcare provider may recommend raising your dose of Invokana. The right dose of Invokana will also be based on your kidney lab results, as well as how well you manage to tolerate the medication.

5. Other medications that affect UGT

Phenobarbital and phenytoin aren’t the only medications that affect the UGT enzyme. Rifampin (Rifadin), ritonavir (Norvir), and other medications that contain ritonavir (like Paxlovid), also do the same. Like phenytoin and phenobarbital, these medications induce the UGT enzyme, which would break down Invokana too quickly.

If you’re taking these medications together, your healthcare provider may need to raise your dose of Invokana for better blood glucose-lowering effects. In some instances, you may need to switch to another diabetes medication to see the effects that you need.

6. Lithium

Lithium (Lithobid) treats bipolar disorder, and it has many interactions. Taking lithium and Invokana together is no exception.

Invokana can remove lithium from your body the same way it removes glucose and sodium. So starting Invokana while you’re taking lithium can lead to lower-than-normal lithium levels. This makes it harder to treat bipolar disorder.

It’s important to always have the right amount of lithium in the body. But lithium levels are very sensitive to changes. When you’re taking lithium, your healthcare provider will routinely check how much lithium is in your blood to make sure you’re taking the right dose. They’ll likely pay even closer attention if you’re taking Invokana.

Good to know: If you’re taking lithium with Invokana, it’s important to stick to a strict dosing schedule. Skipping a dose of Invokana or taking extra doses can affect your lithium levels.

7. Digoxin

Digoxin (Lanoxin) is a heart medication with many interactions. Like lithium, blood levels are closely tracked since it’s dangerous to take too little or too much digoxin.

Taking Invokana with digoxin is generally not recommended. Combining them can raise digoxin levels. High digoxin levels can be toxic. Symptoms of digoxin toxicity include nausea, vomiting, or persistent diarrhea. You can also have a fluttering heartbeat, difficulty breathing, and vision issues.

If you need to take this combination, your healthcare provider will closely track your blood levels of digoxin.

8. Urine glucose lab test

Invokana and other SGLT2 inhibitors can affect a lab test called the urine glucose test. You will likely get a positive result on this test when you take Invokana.

Normally, a positive test would show your blood glucose is too high and your kidneys are trying to get rid of extra glucose through the urine. But if you’re taking an SGLT2 inhibitor, your test is likely to be positive because of the medication.

If you’re taking Invokana, this lab test is not a recommended method of monitoring your blood glucose levels.

When should I contact a healthcare provider about an Invokana interaction?

Talk to a pharmacist or other healthcare provider if you take any of these medications and are thinking about starting Invokana. If you’ve already been taking Invokana with one or more of these medications, talk with your provider as soon as possible. They can help you decide if any adjustments need to be made to your medication regimen.

Keep in mind that this list doesn’t include every medication that interacts with Invokana. Provide your complete medication list — including prescriptions, supplements, and vitamins — to your provider and pharmacist so they can check for other possible interactions.

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Written by:

Hindu Rao, PharmD, APh, BCACP

Hindu Rao, PharmD, APh, BCACP is a clinical assistant professor of pharmacy practice at Chapman University School of Pharmacy and a clinical pharmacist at Providence Medical Foundation. She specializes in chronic disease management and has her board certification in ambulatory care.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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