Canagliflozin/​Metformin

DEA Class; Rx

Common Brand Names; Invokamet, Invokamet-XR

Indicated for the treatment of type 2 diabetes mellitus in combination with diet and exercise when treatment with both canagliflozin and metformin is appropriate.

Alcohol is known to potentiate the effect of metformin on lactate metabolism

Shock from various causes (eg, acute CHF, acute MI, and other conditions characterized by hypoxemia) has been associated with lactic acidosis and may also cause prerenal azotemia

Withholding of food and fluids during surgical or other procedures may increase risk for volume depletion, hypotension and renal impairment

Before initiating therapy, obtain an estimated glomerular filtration rate and obtain an eGFR at least annually; assess more frequently in patients at increased risk for development of renal impairment

Consider temporarily discontinuing in settings of reduced oral intake or fluid losses; if acute kidney injury occurs, discontinue and promptly treat; monitor renal function during therapy

Hyperkalemia reported with canagliflozin; monitor potassium levels in patients with impaired renal function and in patients predisposed to hyperkalemia

Canagliflozin increases risk for genital mycotic infections; treat if indicated

Increases risk of urinary tract infections (UTIs), including life-threatening urosepsis and pyelonephritis that started as UTIs; evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated

Metformin may lower vitamin B12 levels without manifestations; monitor hematologic parameters annually

Increased risk of bone fracture, occurring as early as 12 weeks after treatment initiation, reported; consider factors that contribute to fracture risk prior to initiating therapy

Hypersensitivity reactions, including angioedema and anaphylaxis reported with canagliflozin; these reactions generally occurred within hours to days after initiating canagliflozin; if hypersensitivity reactions occur, discontinue therapy; treat and monitor until signs and symptoms resolve

>10%

canagliflozin

• Female genital mycotic infections (10.4-11.4%)

metformin

• Diarrhea (53.2%)
• Nausea/vomiting (25.5%)
• Flatulence (12.1%)

1-10%

canagliflozin

• Increased urination (4.6-5.3%)
• Male genital mycotic infections (3.7-4.2%)
• Vulvovaginal pruritus (1.6-3%)
• Thirst (2.3-2.8%)
• Falls (1.3-2.1%)
• Constipation (1.8-2.3%)
• Bone fractures (1.1-1.5%)
• Nausea (2.2-2.3%)
• Abdominal pain (1.7-1.8%)

• volume depletion

  • Overall population (2.3-3.4%)
  • Age >75 yr (4.9-8.7%)
  • eGFR <60/mL/min/1.73 mL² (4.7-8.1%)
  • Use of loop diuretic (3.2-8.8%)

metformin

• Asthenia (9.2%)
• Indigestion (7.1%)
• Abdominal discomfort (6.4%)
• Headache (5.7%)

Alcohol is known to potentiate the effect of metformin on lactate metabolism

Shock from various causes (eg, acute CHF, acute MI, and other conditions characterized by hypoxemia) has been associated with lactic acidosis and may also cause prerenal azotemia

Withholding of food and fluids during surgical or other procedures may increase risk for volume depletion, hypotension and renal impairment

Before initiating therapy, obtain an estimated glomerular filtration rate and obtain an eGFR at least annually; assess more frequently in patients at increased risk for development of renal impairment

Consider temporarily discontinuing in settings of reduced oral intake or fluid losses; if acute kidney injury occurs, discontinue and promptly treat; monitor renal function during therapy

Hyperkalemia reported with canagliflozin; monitor potassium levels in patients with impaired renal function and in patients predisposed to hyperkalemia

Canagliflozin increases risk for genital mycotic infections; treat if indicated

Increases risk of urinary tract infections (UTIs), including life-threatening urosepsis and pyelonephritis that started as UTIs; evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated

Metformin may lower vitamin B12 levels without manifestations; monitor hematologic parameters annually

Increased risk of bone fracture, occurring as early as 12 weeks after treatment initiation, reported; consider factors that contribute to fracture risk prior to initiating therapy

Hypersensitivity reactions, including angioedema and anaphylaxis reported with canagliflozin; these reactions generally occurred within hours to days after initiating canagliflozin; if hypersensitivity reactions occur, discontinue therapy; treat and monitor until signs and symptoms resolve

Canagliflozin

• Based on animal data showing adverse renal effects, not recommended during the second and third trimesters of pregnancy

• Data are limited in pregnant women and are not sufficient to determine a drug associated risk for major birth defects or miscarriage

Metformin

• Metformin was not teratogenic in rats and rabbits at doses up to 600 mg/kg/day; determination of fetal concentrations demonstrated a partial placental barrier to metformin

Breastfeeding not recommended

Canagliflozin/metformin

tablet

• 50mg/500mg
• 50mg/1000mg
• 150mg/500mg
• 150mg/1000mg

tablet, extended-release

• 50mg/500mg
• 50mg/1000mg
• 150mg/500mg
• 150mg/1000mg