Meta Information
ID:sglt2-inhibitors
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/diuretics
Target name:
Diuretics (Water Pills)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Empagliflozin acts as an osmotic diuretic; combining it with other diuretics greatly increases the risk of volume depletion, dehydration, low blood pressure, and kidney injury.
Actionable advice:
This should be used with extreme caution, and close monitoring of hydration, blood pressure, and kidney function is important.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Clinical Impact Coadministration of empagliflozin with diuretics resulted in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.
Label source:
FDA label: Empagliflozin (Jardiance)
Action type:
monitor
Target id:
/intervention/insulin
Target name:
Insulin
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Empagliflozin lowers blood glucose independently of insulin. When combined with insulin, the risk of severe hypoglycemia (low blood sugar) is significantly increased.
Actionable advice:
The dose of insulin will likely need to be reduced when starting empagliflozin; monitor blood glucose frequently.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Intervention Coadministration of JARDIANCE with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower dosages of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.
Label source:
FDA label: Empagliflozin (Jardiance)
Action type:
adjust_with_prescriber
Target id:
/class/antidiabetic-medications
Target name:
Insulin and Insulin Secretagogues (e.g., Sulfonylureas) (Canagliflozin)
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:
/dietary/ketogenic-diet
Target name:
Ketogenic Diet
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both empagliflozin and a ketogenic diet promote the production of ketones. Their combined use dramatically increases the risk of developing euglycemic ketoacidosis, a serious medical emergency where the blood becomes too acidic even with normal blood sugar.
Actionable advice:
A strict ketogenic diet should not be followed while taking empagliflozin.
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: Empagliflozin (Jardiance)
Action type:
avoid
Target id:
/procedure/major-surgery
Target name:
Major Surgery or Procedure (Metabolic)
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
72
Hours after target:
null
Description:
The metabolic stress of surgery, combined with required fasting, increases the risk of euglycemic ketoacidosis. Empagliflozin must be temporarily discontinued to mitigate this risk.
Actionable advice:
Empagliflozin 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:
Temporary Interruption for Surgery Withhold JARDIANCE for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting.
Label source:
FDA label: Empagliflozin (Jardiance)
Action type:
informational_none
Target id:
/condition/dehydration
Target name:
Dehydration or Inadequate Fluid Intake (Canagliflozin)
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/renal-impairment
Target name:
Severe Renal Impairment (eGFR < 30) (Empagliflozin)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Empagliflozin is not recommended for patients with severely impaired kidney function (eGFR < 30 mL/min/1.73 m2) as its glucose-lowering effectiveness is reduced and the risk of adverse effects increases.
Actionable advice:
This should not be used in severe kidney disease; regular monitoring of kidney function is required for all users.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Data Empagliflozin dosed directly to juvenile rats from postnatal day (PND) 21 until PND 90 at doses of 1, 10, 30, and 100 mg/kg/day caused increased kidney weights and renal tubular and pelvic dilatation at 100 mg/kg/day, which approximates 13-times the maximum clinical dose of 25 mg, based on AUC.
Label source:
FDA label: Empagliflozin (Jardiance)
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:
Empagliflozin is not recommended during the second and third trimesters of pregnancy due to potential risks of adverse kidney development and function in the fetus.
Actionable advice:
This should be strictly avoided during pregnancy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Risk Summary Based on animal data showing adverse renal effects, JARDIANCE is not recommended during the second and third trimesters of pregnancy.
Label source:
FDA label: Empagliflozin (Jardiance)
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 empagliflozin passes into breast milk, but due to the potential for serious adverse reactions in a nursing infant, it is not recommended.
Actionable advice:
It should be avoided completely 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:
Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney.
Label source:
FDA label: Empagliflozin (Jardiance)
Action type:
avoid
Target id:
/condition/type-1-diabetes
Target name:
Type 1 Diabetes (Patients)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Use in patients with Type 1 Diabetes is associated with a much higher risk of developing diabetic ketoacidosis (DKA), even with normal or only mildly elevated blood sugar levels.
Actionable advice:
Use should be avoided in Type 1 Diabetes unless under the strict supervision of an endocrinologist.
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 co-transporter 2 (SGLT2) inhibitors compared to patients who received placebo and fatal ketoacidosis has occurred with JARDIANCE.
Label source:
FDA label: Empagliflozin (Jardiance)
Action type:
avoid
Target id:
/dietary/water
Target name:
Adequate Fluid Intake
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Empagliflozin causes fluid and glucose loss through urination. Maintaining adequate hydration is essential to prevent dehydration, low blood pressure, and kidney problems.
Actionable advice:
Drink plenty of fluids throughout the day to stay well-hydrated.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Inform patients that dehydration may increase the risk for hypotension, and to maintain adequate fluid intake.
Label source:
FDA label: Empagliflozin (Jardiance)
Action type:
informational_none
Target id:
/class/nephrotoxic-agents
Target name:
Nephrotoxic Agents (NSAIDs, ACEi, ARBs)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining empagliflozin with drugs like NSAIDs, ACE inhibitors, or ARBs can impair kidney function, especially during illness or dehydration, increasing the risk of acute kidney injury.
Actionable advice:
This combination is best used with caution, with adequate hydration and regular monitoring of kidney function.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
( 5.2 ) • Monitor carefully in patients with impaired hepatic ( 5.4 ) or renal function ( 5.5 ) • Avoid concomitant use of an ACE inhibitor and angiotensin receptor blocker ( 5.6) 5.1 Fetal Toxicity Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity an
Label source:
FDA label: Telmisartan (target-side evidence)
Action type:
monitor
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:
Excessive alcohol consumption can increase the risk of both hypoglycemia and ketoacidosis, and can worsen dehydration caused by empagliflozin.
Actionable advice:
Alcohol intake 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 insulin 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: Empagliflozin (Jardiance)
Action type:
avoid
Target id:
/class/broad-spectrum-inducers
Target name:
UGT Enzyme Inducers (e.g., Rifampin, Phenytoin)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Certain medications (like rifampin) can accelerate the breakdown of empagliflozin via UGT enzymes, reducing its concentration in the blood and potentially making it less effective.
Actionable advice:
If co-administration is necessary, monitor blood glucose closely as a higher dose of empagliflozin may be needed.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Pfizer, adjustments—the clinically effective serum total concentration is 10 to Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or 20 mcg/mL (unbound phenytoin concentration is 1 to 2 mcg/mL).
Label source:
FDA label: Phenytoin (target-side evidence)
Action type:
monitor
Target id:
/intervention/lithium
Target name:
Lithium
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Empagliflozin's diuretic effect can increase the kidney's excretion of lithium, potentially lowering its blood levels and reducing its therapeutic effect for mood stabilization.
Actionable advice:
Lithium levels should be monitored closely if starting or stopping empagliflozin, and dose adjustments may be required.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Clinical Impact Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations.
Label source:
FDA label: Empagliflozin (Jardiance)
Action type:
adjust_with_prescriber
Target id:
/condition/geriatric
Target name:
Geriatric (Older Adults)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Older adults may be more susceptible to the diuretic effects of empagliflozin, leading to a higher risk of dehydration, low blood pressure, dizziness, and falls.
Actionable advice:
This is best used with caution in older adults, with adequate hydration and monitoring for dizziness.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The risk of volume depletion-related adverse reactions increased in patients who were 75 years of age and older to 2.1%, 2.3%, and 4.4% for placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg.
Label source:
FDA label: Empagliflozin (Jardiance)
Action type:
monitor
Target id:
/circadian/wake
Target name:
Waking Up / Morning Routine
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
null
Hours after target:
1
Description:
Taking empagliflozin in the morning allows its diuretic effect to occur primarily during waking hours, reducing the likelihood of sleep disruption from nighttime urination (nocturia).
Actionable advice:
A dose is generally best taken once daily in the morning, with or without food.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Recommended dosage is 10 mg orally once daily in the morning
Label source:
FDA label: Empagliflozin (Jardiance) — DOSAGE AND ADMINISTRATION (2.2)
Action type:
informational_none
Target id:
/class/glucose-lowering-supplements
Target name:
Glucose-Lowering Supplements (e.g., Berberine)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Supplements that lower blood sugar can have an additive effect with empagliflozin, slightly increasing the risk of hypoglycemia.
Actionable advice:
It is a good idea to check blood glucose levels when adding new glucose-lowering supplements to a regimen.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Our results showed that berberine combined with canagliflozin (BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone.
Label source:
PubMed: Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice. (PMID 27507202)
Action type:
monitor
Target id:
/biomarker/urine-glucose-test
Target name:
Urine Glucose Test
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Empagliflozin works by causing glucose to be excreted in the urine. Therefore, urine glucose tests will always be positive and cannot be used to monitor blood sugar control.
Actionable advice:
Urine glucose tests should not be used to monitor blood sugar; blood tests like HbA1c or a blood glucose meter are appropriate instead.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Intervention Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors.
Label source:
FDA label: Empagliflozin (Jardiance)
Action type:
avoid
Target id:
/biomarker/1-5-ag-assay
Target name:
1,5-anhydroglucitol (1,5-AG) Assay
Severity:
major
Interaction type:
assay_interference
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
SGLT2 inhibitors like empagliflozin interfere with the 1,5-AG assay, a test for short-term glycemic control, making its results unreliable.
Actionable advice:
The 1,5-AG assay should not be used for monitoring blood sugar control 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:
Clinical Impact Measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. 11 Reference ID: 5683490 Intervention Monitoring glycemic control with 1,5-AG assay is not recommended.
Label source:
FDA label: Empagliflozin (Jardiance)
Action type:
monitor
Target id:
/biomarker/hematocrit
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 causing plasma volume contraction, empagliflozin can cause a small, expected increase in hematocrit (the proportion of red blood cells).
Actionable advice:
A slight increase in hematocrit is a normal and expected finding on lab tests.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The range of mean baseline LDL-C levels was 90.3 to 90.6 mg/dL across treatment groups. 10 Reference ID: 5683490 Increase in Hematocrit In a pool of four placebo-controlled trials in adults, median hematocrit decreased by 1.3% in placebo and increased by 2.8% in JARDIANCE 10 mg and 2.8% in JARDIANCE 25 mg treated patients.
Label source:
FDA label: Empagliflozin (Jardiance)
Action type:
monitor
Target id:
/biomarker/ldl-c
Target name:
LDL Cholesterol
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Empagliflozin can cause a small, dose-dependent increase in LDL cholesterol levels, which should be monitored as part of routine care.
Actionable advice:
It is a good idea to check lipid panels periodically; this small increase is generally outweighed by the drug's cardiovascular benefits.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
LDL-C increased by 2.3%, 4.6%, and 6.5% in patients treated with placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively.
Label source:
FDA label: Empagliflozin (Jardiance)
Action type:
monitor
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:
/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:
/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/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:
/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:
/class/cns-depressants
Target name:
CNS Depressants
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
General caution when combined with other active therapeutic agents.
Actionable advice:
It is important to talk to a physician before combining this with other medications.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Generic placeholder row: the text is non-specific ('general caution') and there is no established CNS-depressant interaction for this agent. No validatable interaction claim - marked unvalidatable (candidate for removal).
Action type:
informational_none