Diacana

• Type 2 Diabetes Mellitus (T2DM):
  Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.
• Cardiovascular Risk Reduction:
  To reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes and established cardiovascular disease.
• Diabetic Kidney Disease:
  Indicated to reduce the risk of end-stage renal disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes and diabetic nephropathy.
• Off-label Uses:
  Investigational use for heart failure with reduced ejection fraction and weight management adjunct.

• Adults:
  Start with 100 mg orally once daily before the first meal of the day.
  Dose may be increased to 300 mg once daily based on glycemic response and tolerability.
• Elderly:
  No dose adjustment necessary; renal function monitoring recommended.
• Renal Impairment:
  Not recommended in patients with estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m².
  Use caution if eGFR is between 30 and 45 mL/min/1.73 m².
• Pediatrics:
  Safety and efficacy have not been established.
• Administration Route:
  Oral administration with or without food, preferably prior to the first meal.

Canagliflozin hemihydrate selectively inhibits the sodium-glucose co-transporter 2 (SGLT2) located in the proximal renal tubules. This inhibition decreases renal glucose reabsorption and increases urinary glucose excretion, leading to reduced plasma glucose levels. The resulting glycosuria also produces osmotic diuresis and natriuresis, which help reduce blood pressure and body weight, contributing to cardiovascular and renal protective effects.

• Absorption: Rapidly absorbed with peak plasma concentration reached within 1 to 2 hours after dosing.
• Bioavailability: Approximately 65%.
• Distribution: Highly protein-bound (~99%).
• Metabolism: Mainly metabolized by O-glucuronidation via UDP-glucuronosyltransferase enzymes UGT1A9 and UGT2B4; minor metabolism by CYP3A4.
• Elimination Half-life: Approximately 10 to 13 hours.
• Excretion: Eliminated primarily via feces (~41%) and urine (~33%) as metabolites and unchanged drug.

• Pregnancy: No adequate human data. Animal studies have shown potential fetal harm at high doses. Use during pregnancy only if the potential benefit justifies the potential risk.
• Lactation: It is unknown whether canagliflozin is excreted in human milk. Breastfeeding is generally not recommended during treatment.
• Caution advised when prescribing to pregnant or breastfeeding women.

• Primary: Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor
• Subclass: Antidiabetic Agent

• Known hypersensitivity to canagliflozin or any excipients.
• Type 1 diabetes mellitus or diabetic ketoacidosis.
• Severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease.
• Pregnancy and lactation unless benefits clearly outweigh risks.

• Risk of ketoacidosis, including euglycemic diabetic ketoacidosis. Discontinue if suspected.
• Monitor for volume depletion and hypotension, especially in elderly and patients on diuretics.
• Increased incidence of genital mycotic infections and urinary tract infections.
• Monitor renal function before and during therapy.
• Increased risk of lower limb amputations observed; assess risk factors such as peripheral vascular disease and neuropathy.
• Caution in patients with osteoporosis or risk factors for bone fractures.

Common:

• Genital fungal infections (vaginal candidiasis, balanitis)
• Urinary tract infections
• Increased urination
• Thirst
• Constipation or diarrhea

Less common:

• Hypoglycemia (when used with insulin or sulfonylureas)
• Hypotension
• Nausea

Rare but serious:

• Diabetic ketoacidosis
• Acute kidney injury
• Hypersensitivity reactions (rash, angioedema)
• Lower limb amputations
• Fournier’s gangrene (necrotizing fasciitis of the perineum)

• Increased hypoglycemia risk when combined with insulin or insulin secretagogues.
• Concomitant use with diuretics may increase risk of volume depletion and hypotension.
• Minor interactions via CYP3A4; monitor for changes in drug efficacy with strong CYP3A4 inducers or inhibitors.
• Use caution with other nephrotoxic or blood pressure–lowering agents.

• ADA and EASD recommend SGLT2 inhibitors like canagliflozin for patients with T2DM and cardiovascular or renal disease.
• FDA added warnings about ketoacidosis and amputations; recommend patient monitoring.
• EMA highlights rare cases of severe genital infections and advises prompt treatment.

• Store at controlled room temperature, 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in tightly closed containers.
• Keep out of reach of children.
• Do not freeze or refrigerate.