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Invokana
canagliflozin
Adult Dosing .
Dosage forms: TAB: 100 mg, 300 mg
diabetes mellitus, type 2
- [100-300 mg PO qd]
- Start: 100 mg PO qd; Max: 300 mg/day; Info: give before 1st meal; hold tx at least 3 days before surgery/procedure if prolonged fasting
cardiovascular event risk reduction - DM type 2 patients w/ estab. cardiovascular dz
- [100 mg PO qd]
- Max: 300 mg/day; Info: give before 1st meal; may incr. dose to 300 mg PO qd if additional glycemic control needed; hold tx at least 3 days before surgery/procedure if prolonged fasting
kidney dz progression and cardiovascular-associated risk reduction - DM type 2 patients w/ nephropathy and albuminuria >300 mg/day
- [100 mg PO qd]
- Max: 300 mg/day; Info: give before 1st meal; may incr. dose to 300 mg PO qd if additional glycemic control needed; hold tx at least 3 days before surgery/procedure if prolonged fasting
renal dosing
- [diabetes mellitus, type 2]
- eGFR 30-59: max 100 mg/day; eGFR <30: avoid use for glycemic control
- HD/PD: not defined
- [all other indications]
- eGFR 30-59: max 100 mg/day; eGFR <30: avoid tx initiation; Info: if eGFR <30 during tx, may cont. 100 mg qd in patients w/ albuminuria >300 mg/day
- HD/PD: not defined
hepatic dosing
- [see below]
- Child-Pugh Class A or B: no adjustment; Child-Pugh Class C: not defined
Peds Dosing .
- Dosage forms: TAB: 100 mg, 300 mg
diabetes mellitus, type 2
- [10 yo and older]
- Dose: 100-300 mg PO qd; Start: 100 mg PO qd; Max: 300 mg/day; Info: give before 1st meal; hold tx at least 3 days before surgery/procedure if prolonged fasting
renal dosing
- [see below]
- eGFR 30-59: max 100 mg/day; eGFR <30: avoid use for glycemic control
- HD/PD: not defined
hepatic dosing
- [see below]
- Child-Pugh Class A or B: no adjustment; Child-Pugh Class C: not defined
Contraindications / Cautions .
- hypersensitivity to drug or ingredient
- pregnancy 2nd trimester
- pregnancy 3rd trimester
- breastfeeding
- eGFR <30
- caution: elderly patients
- diabetic ketoacidosis
- volume depletion
- caution: pregnancy 1st trimester
- caution: eGFR <60
- caution: hypotension
- caution: ketoacidosis risk
- caution: pancreatic disorder
- caution: fasting
- caution: febrile illness, acute
- caution: surgery
- caution: ketogenic diet
- caution: alcohol abuse
- caution: genital mycotic infection history
- caution: uncircumcised penis
- caution: fracture risk
- caution: amputation history
- caution: PVD
- caution: neuropathy
- caution: diabetic foot ulcer
- caution: osteomyelitis
- caution: gangrene
Drug Interactions .
Overview
canagliflozin
SGLT2 inhibitor
- UGT1A9 substrate
- UGT2B4 substrate
- P-gp inhibitor, weak
- antidiabetic agent
- fluid/electrolyte loss
- hypotensive effects
Avoid/Use Alternative
- apixaban
- bexagliflozin
- canagliflozin
- dabigatran
- empagliflozin
- ensartinib
- ertugliflozin
- futibatinib
- lofexidine
- neratinib
- pralsetinib
- relugolix
- repotrectinib
- sirolimus albumin-bound
- sotagliflozin
- topotecan
- venetoclax
Monitor/Modify Tx
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- vosoritide
- yohimbe
- ziprasidone
Caution Advised
- darolutamide
- glecaprevir
- naldemedine
- pibrentasvir
Adverse Reactions .
Serious Reactions
- hypersensitivity rxn
- anaphylaxis
- acute kidney injury
- ketoacidosis
- UTI, serious
- hypotension, orthostatic
- pancreatitis
- bone density loss
- fractures
- lower limb amputation risk
- Fournier gangrene
- renal cell CA risk
Common Reactions
- hyperkalemia
- genital mycotic infection
- cholesterol incr.
- magnesium incr.
- hypoglycemia
- UTI
- urination incr.
- phosphate incr.
- Hgb incr.
- vulvovaginal pruritus
- thirst
- hypotension, orthostatic
- constipation
- nausea
- fatigue
- Cr incr.
- lower limb amputation risk
Safety/Monitoring .
Monitoring Parameters
Cr at baseline, then as clinically indicated; BP; consider urine ketones if ketoacidosis risk
Pregnancy/Lactation .
Pregnancy
Clinical Summary
avoid use in 2nd and 3rd trimester, weigh risk/benefit in 1st trimester; inadequate human data available; risk of irreversible adverse effects on renal development and maturation in 2nd and 3rd trimesters based on animal data at 0.5x systemic exposure and drug's mechanism of action; no known risk of teratogenicity in 1st trimester based on animal data at up to 19x recommended human dose
Lactation
Clinical Summary
avoid use while breastfeeding; no human data available, though possible risk of adverse effects on infant renal development and maturation based on drug's mechanism of action; no human data available to assess effects on milk production
Pharmacology .
Metabolism: liver; CYP450: minimal (7%); 3A4 substrate; UGT: 1A9, 2B4 substrate
Excretion: feces 51.7% (41.5% unchanged), urine 33% (<1% unchanged); Half-life: 10.6-13.1h
Subclass: Diabetes: SGLT2 Inhibitors ; SGLT2 Inhibitors, Cardiovascular ; SGLT2 Inhibitors, Nephrological
Mechanism of Action
inhibits sodium-glucose cotransporter 2 (SGLT2), reducing glucose and sodium reabsorption, incr. urinary glucose excretion and sodium delivery to distal tubule; may incr. tubuloglomerular feedback and decr. intraglomerular pressure
Formulary .
No Formulary Selected
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