糖尿病 (SGLT2I)、糖尿病腎病變<20210405>
1. Diabetes mellitus, type 2: Treatment of type 2 diabetes mellitus (noninsulin dependent, NIDDM) as an adjunct to diet and exercise to improve glycemic control
2. Diabetic nephropathy: With urinary albumin excretion >300 mg/day.<20210405>
#仿單變更2021

By inhibiting sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules, canagliflozin reduces reabsorption of filtered glucose from the tubular lumen and lowers the renal threshold for glucose (RTG). SGLT2 is the main site of filtered glucose reabsorption; reduction of filtered glucose reabsorption and lowering of RTG result in increased urinary excretion of glucose, thereby reducing plasma glucose concentrations.

Absorption:
1. Not affected by food; however, administration prior to the first meal of the day may delay intestinal glucose absorption, thereby reducing postprandial hyperglycemia
2. Bioavailability: ~65%
Distribution:
Protein binding: 99% mainly to albumin
Metabolism:
Major metabolism through O-glucuronidation by UGT1A9 and UGT2B4 to two inactive metabolites; minor oxidative metabolism (~7%) through CYP3A4
Excretion: Feces (41.5% as unchanged drug, 7% as hydroxylated metabolite, 3.2% as O-glucuronide metabolite); urine ~33% (30.5% as O-glucuronide metabolites, <1% as unchanged drug)
Phsrmacodynamics:
1. Half-life elimination: 100 mg dose: 10.6 hours; 300 mg dose: 13.1 hours
2. Time to peak, plasma: 1 to 2 hours
3. Onset of action: Within 24 hours (dose-dependent)
4. Duration of action: Suppression of the renal threshold for glucose (RTG) occurs throughout the 24-hour dosing interval; maximal RTG suppression occurred with the 300 mg dose (RTG decreased from baseline of ~240 mg/dL to a mean of 70 to 90 mg/dL over 24 hours)

1. History of serious hypersensitivity to canagliflozin or any component of the formulation
2. Severe renal impairment (eGFR <30 mL/minute/1.73 m2); end-stage renal disease or patients on dialysis

Based on animal data, adverse fetal effects on renal development may occur in humans following in utero exposure during the second and third trimesters.

It is not known if canagliflozin is present in breast milk. Breastfeeding is not recommended by the manufacturer.

>10%:
Increased serum potassium (more risk in patients with moderate renal impairment), genitourinary infection (females: 11% to 12%; including vulvovaginal candidiasis, vulvovaginal mycotic infection, vulvovaginitis, vaginal infection, vulvitis; males: 4%; including balanitis/balanoposthitis, balanitis candida, fungal genital infection)

1% to 10%:
Falling, fatigue,hypoglycemia, increased thirst, abdominal pain, constipation, nausea, urinary tract infection, increased urine output, vulvovaginal pruritus, hypersensitivity reaction, amputation, weakness, renal insufficiency

Initial 100 mg once daily prior to first meal of the day; may increase to 300 mg once daily (only in patients with eGFR ≥60 mL/minute/1.73 m²)

eGFR >30 mL/minute/1.73 m2: (Adult) 100 mg once daily.<20210405>
eGFR <30 mL/minute/1.73 m2: Use is contraindicated.
End-stage renal disease (ESRD): Use is contraindicated.
Hemodialysis: Use is contraindicated.

Mild-to-moderate impairment (Child-Pugh class A, B): No dosage adjustment necessary. Severe impairment (Child-Pugh class C): Use not recommended (has not been studied).