Generic Name

Canagliflozin and Metformin Hydrochloride

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Classification

FDA Approved Indications

• Type 2 Diabetes Mellitus

Mechanism of Action

Canagliflozin inhibits the sodium-glucose co-transporter 2 (SGLT2) in the proximal renal tubules, reducing glucose reabsorption and increasing urinary glucose excretion. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity.

Dosage and Administration

Adult: Initial dose of canagliflozin 100-300 mg once daily; metformin dose adjusted according to renal function and tolerability, usually starting at 500 mg twice daily

Pediatric: Not approved for pediatric use

Geriatric: Start at lower doses due to renal function considerations, monitor renal function regularly

Renal Impairment: Adjust dose based on renal function; contraindicated if eGFR <30 mL/min/1.73 m²

Hepatic Impairment: Use with caution; contraindicated in severe hepatic impairment

Pharmacokinetics

Absorption: Canagliflozin is well absorbed; food does not affect absorption

Distribution: High plasma protein binding for canagliflozin; extensive distribution for metformin

Metabolism: Canagliflozin is metabolized minimally; metformin undergoes negligible metabolism

Excretion: Renally excreted; canagliflozin 50-60% unchanged in urine, metformin 90% in urine

Half Life: Canagliflozin approximately 10.6 hours; metformin approximately 17.6 hours

Contraindications

• Renal impairment (eGFR <30 mL/min/1.73 m²)
• Metabolic acidosis
• Hypersensitivity to components

Precautions

• Risk of ketoacidosis, urinary tract infections, hypotension, dehydration, and lactic acidosis (metformin)

Adverse Reactions - Common

• Genital mycotic infections (Common)
• Urinary tract infections (Common)
• Hypoglycemia when combined with insulin or insulin secretagogues (Less common)

Adverse Reactions - Serious

• Lactic acidosis (metformin) (Rare)
• Ketoacidosis (Rare)
• Severe urinary tract infections or Fournier's gangrene (Rare)

Drug-Drug Interactions

• Diuretics, ACE inhibitors, ARBs (risk of hypotension or renal function decline)
• Other hypoglycemic agents (risk of hypoglycemia)

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Take medication with food to reduce gastrointestinal side effects.
• Maintain hydration; report symptoms of dehydration, urinary infections, or ketoacidosis.
• Monitor blood glucose regularly.
• Avoid excessive alcohol intake.
• Be aware of symptoms of lactic acidosis: unusual weakness, fatigue, muscle pain, difficulty breathing.

Special Considerations

Black Box Warnings:

• Lactic acidosis (metformin)

Genetic Factors: N/A

Lab Test Interference: May interfere with serum creatinine and blood glucose assessments

Overdose Management

Signs/Symptoms: Severe hypoglycemia, lactic acidosis, dehydration signs

Treatment: Discontinue medication, supportive care, manage hydration, and correct acidosis if present

Storage and Handling

Storage: Store at room temperature, 20-25°C, away from moisture and light

Stability: Stable under recommended storage conditions