Meta Information
ID:canagliflozin
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/antidiabetic-medications
Target name:
Insulin and Insulin Secretagogues (e.g., Sulfonylureas)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining canagliflozin with medications that strongly lower blood sugar, like insulin or sulfonylureas, significantly increases the risk of severe hypoglycemia (dangerously low blood sugar).
Actionable advice:
Your doctor will likely need to reduce the dose of your insulin or other diabetes medication when starting canagliflozin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
ents for signs and symptoms of urinary tract infections and treat promptly, if indicated ( 5.4 ). • Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues : Consider a lower dose of insulin or the insulin secretagogue to reduce the risk of hypoglycemia when used in combination with INVOKANA ( 5.5 ). • Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) : Serious, life-thre
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
adjust_with_prescriber
Target id:
/class/loop-diuretics
Target name:
Loop Diuretics (e.g., Furosemide)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both canagliflozin and loop diuretics cause fluid and salt loss, and using them together can lead to severe dehydration, low blood pressure, and acute kidney injury.
Actionable advice:
Concurrent use should be avoided unless closely monitored by a physician, who may need to adjust diuretic dosage.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
(because of bladder emptying disorders, prostatic hyperplasia, urethral narrowing), the administration of furosemide can cause acute urinary retention related to increased production and retention of urine.
Label source:
FDA label: Furosemide (target-side evidence)
Action type:
avoid
Target id:
/class/broad-spectrum-inducers
Target name:
UGT Enzyme Inducers (e.g., Rifampin, Phenytoin)
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Certain medications (like rifampin, phenytoin, phenobarbital, ritonavir) speed up the metabolism of canagliflozin, significantly reducing its concentration and effectiveness.
Actionable advice:
If you must take these medications, your doctor may need to increase your canagliflozin dose or choose an alternative.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Examples: Rifampin, phenytoin, phenobarbital, ritonavir Insulin or Insulin Secretagogues Clinical Impact: The risk of hypoglycemia is increased when INVOKANA is used concomitantly with insulin secretagogues (e.g., sulfonylurea) or insulin.
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
informational_none
Target id:
/intervention/ketogenic-diet
Target name:
Ketogenic or Very Low-Carbohydrate Diets
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These diets promote ketone production, and when combined with canagliflozin, they dramatically increase the risk of developing a serious condition called euglycemic diabetic ketoacidosis (DKA).
Actionable advice:
Ketogenic and very low-carbohydrate diets should be avoided while taking canagliflozin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse.
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
avoid
Target id:
/procedure/major-surgery
Target name:
Major Surgical or Medical Procedures
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
72
Hours after target:
null
Description:
The physiological stress of surgery, combined with fasting, increases the risk of diabetic ketoacidosis (DKA). Canagliflozin should be stopped beforehand to mitigate this risk.
Actionable advice:
Canagliflozin should be stopped at least 3 days before any scheduled major surgery or procedure.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
is include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse.
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
informational_none
Target id:
/condition/renal-impairment
Target name:
Moderate to Severe Renal Impairment (eGFR < 45)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The glucose-lowering effect of canagliflozin depends on kidney function; its efficacy is reduced in renal impairment, while the risk of side effects like hyperkalemia and volume depletion increases.
Actionable advice:
This medication should be avoided if eGFR is below 30, and used with caution and likely at a lower dose if eGFR is below 45.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Not recommended when breastfeeding ( 8.2 ). • Geriatrics : Higher incidence of adverse reactions related to reduced intravascular volume ( 8.5 ). • Renal Impairment : Higher incidence of adverse reactions related to hypotension and renal function ( 8.6 ). • Hepatic Impairment : Not recommended in patients with severe hepatic impairment ( 8.7 ). 8.1 Pregnancy Risk Summary Based on juvenile animal d
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
avoid
Target id:
/dietary/meal
Target name:
First Meal of the Day
Severity:
major
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0.5
Hours after target:
0
Description:
Taking canagliflozin before the first meal of the day is crucial for its mechanism of action, as it helps to excrete the glucose absorbed from that meal.
Actionable advice:
The daily dose of canagliflozin should be taken just before the first meal.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
al to reduce postprandial plasma glucose excursions due to delayed intestinal glucose absorption, it is recommended that INVOKANA be taken before the first meal of the day [see Dosage and Administration (2.2) ] .
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
separate
Target id:
/condition/dehydration
Target name:
Dehydration or Inadequate Fluid Intake
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Canagliflozin works by increasing urination, which can lead to dehydration. Being dehydrated significantly increases the risk of low blood pressure, dizziness, and acute kidney injury.
Actionable advice:
Adequate fluid intake should be maintained throughout the day, and caution is warranted during illness or intense exercise.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
verse reactions related to reduced intravascular volume with INVOKANA (such as hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration), particularly with the 300 mg daily dose, compared to younger patients; a more prominent increase in the incidence was seen in patients who were 75 years and older [see Dosage and Administration (2.1) and Adverse Reactions (6.1) ].
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
informational_none
Target id:
/condition/type-1-diabetes
Target name:
Type 1 Diabetes Mellitus
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Canagliflozin is not approved for Type 1 Diabetes due to a significantly increased risk of life-threatening diabetic ketoacidosis (DKA).
Actionable advice:
This medication is contraindicated and should not be used if you have Type 1 Diabetes.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium glucose transporter 2 (SGLT2) inhibitors compared to patients who received placebo; this risk may be greater with higher doses of INVOKANA.
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Canagliflozin is not recommended during the second and third trimesters of pregnancy due to potential risks to fetal kidney development.
Actionable advice:
This medication should be strictly avoided during pregnancy or when planning to become pregnant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
erved in rats when canagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy, at an exposure 0.5-times the 300 mg clinical dose, based on AUC.
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is not known if canagliflozin passes into breast milk, but due to the potential for serious adverse reactions in the nursing infant, it is not recommended.
Actionable advice:
This medication should not be taken while breastfeeding.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Not recommended when breastfeeding ( 8.2 ). • Geriatrics : Higher incidence of adverse reactions related to reduced intravascular volume ( 8.5 ). • Renal Impairment : Higher incidence of adverse reactions related to hypotension and renal function ( 8.6 ). • Hepatic Impairment : Not recommended in patients with severe hepatic impairment ( 8.7 ).
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
avoid
Target id:
/condition/peripheral-vascular-disease
Target name:
Peripheral Vascular Disease or History of Amputation
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Clinical trials showed an increased risk of lower limb amputations, primarily of the toe or foot, in patients with established cardiovascular disease or risk factors.
Actionable advice:
It is important to talk to a doctor about this risk; regular foot exams are critical while taking this medication.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
toms of ketoacidosis and instruct patients to discontinue INVOKANA and seek medical attention immediately if signs and symptoms occur. 5.2 Lower Limb Amputation An increased risk of lower limb amputations associated with INVOKANA use versus placebo was observed in CANVAS (5.9 vs 2.8 events per 1,000 patient-years) and CANVAS-R (7.5 vs 4.2 events per 1,000 patient-years), two randomized, placebo-co
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
informational_none
Target id:
/class/potassium-elevators
Target name:
Potassium-Elevating Agents (ACEi, ARBs, K-Sparing Diuretics)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Canagliflozin can cause a small increase in serum potassium. When combined with other drugs that also raise potassium (like ACE inhibitors or ARBs), the risk of hyperkalemia (high potassium) becomes significant.
Actionable advice:
If taking these medications together, regular monitoring of blood potassium levels is necessary.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
or discontinuing therapy in patients who develop a clinically significant decrease in renal function on valsartan [see Drug Interactions ( 7 )]. 5.4 Hyperkalemia Some patients with heart failure have developed increases in potassium.
Label source:
FDA label: Valsartan (target-side evidence)
Action type:
monitor
Target id:
/class/nsaids
Target name:
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
NSAIDs can reduce kidney blood flow. Combining them with canagliflozin, especially during periods of dehydration, can increase the risk of acute kidney injury.
Actionable advice:
NSAIDs are best used cautiously, with good hydration; long-term concurrent use is best avoided if possible.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal
Label source:
FDA label: Celecoxib (Celebrex) — Section 5.6 Renal Toxicity and Hyperkalemia (target-side evidence for NSAID class)
Action type:
avoid
Target id:
/dietary/alcohol-acute
Target name:
Alcohol (Acute Consumption)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Alcohol can increase the risk of hypoglycemia, contribute to dehydration, and may increase the risk of ketoacidosis when consumed in large amounts.
Actionable advice:
Alcohol consumption is best limited, and binge drinking is best avoided while taking this medication.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
(such as insulin dose reduction or missed doses, infection, reduced caloric intake, ketogenic diet, surgery, dehydration, and alcohol abuse) and symptoms of ketoacidosis (including nausea, vomiting, abdominal pain, tiredness, and labored breathing).
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
avoid
Target id:
/intervention/digoxin
Target name:
Digoxin
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Canagliflozin can slightly increase the concentration of digoxin in the blood, potentially increasing the risk of digoxin toxicity.
Actionable advice:
If you take digoxin, your doctor should monitor your digoxin levels after starting canagliflozin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Canagliflozin increases digoxin exposure [see Clinical Pharmacology (12.3) ] .
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
separate
Target id:
/class/sglt2-inhibitors
Target name:
Other SGLT2 Inhibitors (e.g., Dapagliflozin, Empagliflozin)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Using more than one SGLT2 inhibitor at the same time is redundant therapy, provides no additional benefit, and significantly increases the risk of all associated side effects.
Actionable advice:
More than one medication from the SGLT2 inhibitor class should never be taken at the same time.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Discontinue dapagliflozin tablets, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control. 5.6 Genital Mycotic Infections Dapagliflozin tablets increases the risk of genital mycotic infections.
Label source:
FDA label: Dapagliflozin (target-side evidence)
Action type:
avoid
Target id:
/condition/osteoporosis
Target name:
Osteoporosis or High Fracture Risk
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
An increased risk of bone fractures has been observed in some clinical trials with canagliflozin, with fractures occurring as early as 12 weeks after starting.
Actionable advice:
If you have osteoporosis or are at high risk for fractures, discuss this potential risk with your doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Fracture An increased risk of bone fracture, occurring as early as 12 weeks after treatment initiation, was observed in adult patients using INVOKANA in the CANVAS trial [see Clinical Studies (14.3) ] .
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
informational_none
Target id:
/condition/history-of-yeast-infections
Target name:
History of Genital Mycotic (Yeast) Infections
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
By increasing glucose in the urine, canagliflozin creates a favorable environment for yeast growth, significantly increasing the incidence of genital yeast infections in both men and women.
Actionable advice:
The increased risk is worth keeping in mind; maintaining good hygiene helps, and seeking treatment if symptoms occur is a good idea.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Monitor and treat if indicated ( 5.7 ). • Hypersensitivity Reactions : Discontinue INVOKANA and monitor until signs and symptoms resolve ( 5.8 ). • Bone Fracture : Consider factors that contribute to fracture risk before initiating INVOKANA ( 5.9 ).
Label source:
FDA label: Canagliflozin (Invokana)
Action type:
informational_none
Target id:
/biomarker/lipid-panel
Target name:
LDL Cholesterol Levels
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Canagliflozin can cause a dose-dependent increase in LDL cholesterol ('bad' cholesterol) levels.
Actionable advice:
Regularly monitor your lipid panel as your LDL cholesterol may increase while on this medication.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Dose-related increases in LDL-C occur with INVOKANA
Label source:
FDA label: Canagliflozin (Invokana) — Section 5.11 Increases in Low-Density Lipoprotein (LDL-C)
Action type:
monitor
Target id:
/biomarker/complete-blood-count
Target name:
Hematocrit
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Due to its diuretic effect, canagliflozin can cause volume contraction, leading to a small increase in hematocrit (the proportion of red blood cells in your blood).
Actionable advice:
A small rise in hematocrit is an expected finding and generally not a cause for concern.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
INVOKANA results in an osmotic diuresis
Label source:
FDA label: Canagliflozin (Invokana) — Volume Depletion-Related Adverse Reactions; "Increases in Hemoglobin" section confirms RBC/plasma-volume mechanism behind hematocrit rise
Action type:
monitor