INVOKANA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for INVOKANA (INVOKANA).

How it works

Sodium-glucose cotransporter 2 (SGLT2) inhibitor; reduces renal glucose reabsorption, increasing urinary glucose excretion.

What the body does with it

Metabolism	Primarily via O-glucuronidation by UGT2B4, UGT1A9, and UGT1A1; minor CYP3A4 metabolism; ~33% excreted unchanged in urine, ~51% in feces.
Excretion	Primarily excreted unchanged in urine (33%) and feces (52%) as parent drug and glucuronide metabolites; renal clearance accounts for 70% of total clearance, with 51% renally excreted as unchanged drug.
Half-life	Terminal elimination half-life is 10.6 hours (range 9.5–12.5 h) in healthy subjects; allows once-daily dosing. Half-life increases to 16 hours in moderate renal impairment and 22 hours in severe renal impairment.
Protein binding	94% bound to plasma proteins, primarily to albumin.
Volume of Distribution	Volume of distribution is 118 L (1.69 L/kg for a 70 kg individual), indicating extensive extravascular distribution into tissues beyond plasma volume.
Bioavailability	Oral bioavailability cannot be determined due to lack of an intravenous formulation, but is considered high (65–80%) based on urinary recovery of drug and metabolites; maximum plasma concentration is reached 1–2 hours post-dose.
Onset of Action	Onset of urinary glucose excretion occurs within 24 hours of first oral dose; maximal effect on HbA1c reduction is observed after 4–6 weeks of chronic dosing.
Duration of Action	Duration of action is approximately 24 hours, supporting once-daily dosing. Duration of urinary glucose excretion persists for the dosing interval; clinically, efficacy in glycemic control requires consistent daily administration.

Classification & Brands

Action Class	SGLT2 inhibitors
Brand Substitutes	Prominad Tablet, Sulisent 100mg Tablet

Dosing & administration

100 mg orally once daily, before the first meal of the day; may increase to 300 mg once daily if tolerated and eGFR is adequate.

Dosage form	TABLET
Renal impairment	Initiate only if eGFR >= 30 mL/min/1.73 m2. If eGFR is 30 to <60, continue current dose; if eGFR <30, discontinue. Not recommended for use when eGFR persistently <30.
Liver impairment	No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not recommended for severe hepatic impairment (Child-Pugh C).
Pediatric use	Safety and efficacy in pediatric patients (<18 years) have not been established.
Geriatric use	No initial dose adjustment required; monitor renal function more frequently due to age-related decline in GFR. Use caution in patients >=75 years due to limited therapeutic benefit.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for INVOKANA (INVOKANA).

Breastfeeding	Canagliflozin is excreted into rat milk; human data are absent. The M/P ratio is unknown. Due to potential adverse effects on neonatal renal development, breastfeeding is not recommended during therapy.
Teratogenic Risk	Invokana (canagliflozin) is contraindicated in the second and third trimesters due to associated fetal renal toxicity. First trimester exposure data are limited; animal studies show renal development effects. Use not recommended in pregnancy.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reaction to canagliflozin","Severe renal impairment (eGFR <30 mL/min/1.73 m²) or ESRD on dialysis","Type 1 diabetes mellitus (not approved and may increase DKA risk)"]

Clinical Precautions

Precautions

["Diabetic ketoacidosis (including euglycemic DKA)","Acute kidney injury and impairment in renal function","Urosepsis and pyelonephritis","Lower limb amputation (especially toe amputations)","Hypotension","Hyperkalemia","Genital mycotic infections","Increased LDL-C","Urinary tract infections"]

Clinical Tips & Counseling

Drug interactions

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INVOKANA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for INVOKANA (INVOKANA).

How it works

Sodium-glucose cotransporter 2 (SGLT2) inhibitor; reduces renal glucose reabsorption, increasing urinary glucose excretion.

What the body does with it

Metabolism	Primarily via O-glucuronidation by UGT2B4, UGT1A9, and UGT1A1; minor CYP3A4 metabolism; ~33% excreted unchanged in urine, ~51% in feces.
Excretion	Primarily excreted unchanged in urine (33%) and feces (52%) as parent drug and glucuronide metabolites; renal clearance accounts for 70% of total clearance, with 51% renally excreted as unchanged drug.
Half-life	Terminal elimination half-life is 10.6 hours (range 9.5–12.5 h) in healthy subjects; allows once-daily dosing. Half-life increases to 16 hours in moderate renal impairment and 22 hours in severe renal impairment.
Protein binding	94% bound to plasma proteins, primarily to albumin.
Volume of Distribution	Volume of distribution is 118 L (1.69 L/kg for a 70 kg individual), indicating extensive extravascular distribution into tissues beyond plasma volume.
Bioavailability	Oral bioavailability cannot be determined due to lack of an intravenous formulation, but is considered high (65–80%) based on urinary recovery of drug and metabolites; maximum plasma concentration is reached 1–2 hours post-dose.
Onset of Action	Onset of urinary glucose excretion occurs within 24 hours of first oral dose; maximal effect on HbA1c reduction is observed after 4–6 weeks of chronic dosing.
Duration of Action	Duration of action is approximately 24 hours, supporting once-daily dosing. Duration of urinary glucose excretion persists for the dosing interval; clinically, efficacy in glycemic control requires consistent daily administration.

Classification & Brands

Action Class	SGLT2 inhibitors
Brand Substitutes	Prominad Tablet, Sulisent 100mg Tablet

Dosing & administration

100 mg orally once daily, before the first meal of the day; may increase to 300 mg once daily if tolerated and eGFR is adequate.

Dosage form	TABLET
Renal impairment	Initiate only if eGFR >= 30 mL/min/1.73 m2. If eGFR is 30 to <60, continue current dose; if eGFR <30, discontinue. Not recommended for use when eGFR persistently <30.
Liver impairment	No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not recommended for severe hepatic impairment (Child-Pugh C).
Pediatric use	Safety and efficacy in pediatric patients (<18 years) have not been established.
Geriatric use	No initial dose adjustment required; monitor renal function more frequently due to age-related decline in GFR. Use caution in patients >=75 years due to limited therapeutic benefit.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for INVOKANA (INVOKANA).

Breastfeeding	Canagliflozin is excreted into rat milk; human data are absent. The M/P ratio is unknown. Due to potential adverse effects on neonatal renal development, breastfeeding is not recommended during therapy.
Teratogenic Risk	Invokana (canagliflozin) is contraindicated in the second and third trimesters due to associated fetal renal toxicity. First trimester exposure data are limited; animal studies show renal development effects. Use not recommended in pregnancy.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

Clinical Precautions

Precautions

Clinical Tips & Counseling

Drug interactions

Loading safety data…