Canagliflozin; Uses, Dosage, Side Effects, Drug Interactions

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Canagliflozin anhydrous is a Sodium-Glucose Cotransporter 2 Inhibitor. The mechanism of action of canagliflozin anhydrous is as a Sodium-Glucose Transporter 2 Inhibitor and P-Glycoprotein Inhibitor. Canagliflozin Anhydrous is the anhydrous form of canagliflozin, a C-glucoside with a thiophene ring that is an orally available inhibitor of sodium-glucose transporter 2 (SGLT2) with antihyperglycemic activity. Canagliflozin is also able to reduce body weight and has a low risk for hypoglycemia.

Canagliflozin is a medication used for the treatment of type 2 diabetes. It is of the gliflozin class or subtype 2 sodium-glucose transport (SGLT-2) inhibitors class. Canagliflozin belongs to a new class of anti-diabetic drugs that works by inhibiting the sodium-glucose transport protein (SGLT2). This transport protein is found in the kidney and is responsible for reabsorbing glucose that has been filtered. This mechanism is associated with a low risk of hypoglycemia (too low blood glucose) compared to sulfonylurea derivatives and insulin. In 2017, the FDA concluded that canagliflozin causes an increased risk of leg and foot amputations. The FDA began requiring a Boxed Warning to be added to the canagliflozin drug labels to describe this risk.

Mechanism of Action of Canagliflozin

Canagliflozin is an inhibitor of subtype 2 sodium-glucose transport proteins (SGLT2), which is responsible for at least 90% of renal glucose reabsorption (SGLT1being responsible for the remaining 10%). Blocking this transporter causes up to 119 grams of blood glucose per day to be eliminated through the urine, corresponding to 476 kilocalories. Additional water is eliminated by osmotic diuresis, resulting in a lowering of blood pressure. This mechanism is associated with a low risk of hypoglycemia (too low blood glucose) compared to other types of anti-diabetic drugs such as sulfonylurea derivatives and insulin.

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Sodium-glucose co-transporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Canagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose (RTG), and thereby increases urinary glucose excretion (UGE).

Indications of Canagliflozin

  • Type 2 Diabetes Mellitus
  • Canagliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Use in type 1 diabetes mellitus patients or in the treatment of diabetic ketoacidosis is not recommended.
  • Canagliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Use in type 1 diabetes mellitus patients or in the treatment of diabetic ketoacidosis is not recommended.
  • monotherapy when diet and exercise alone do not provide adequate glycaemic control in patients for whom the use of metformin is considered inappropriate due to intolerance or contraindications.
  • Add on therapy and on therapy with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic cont

Contra-Indications of Canagliflozin

  • Infection
  • Low blood sugar
  • Pituitary hormone deficiency
  • Decreased function of the adrenal gland
  • Inadequate vitamin B12
  • Excess body acid
  • Extreme loss of body water
  • The habit of drinking too much alcohol
  • Alcohol intoxication
  • Heart attack
  • Suddenly serious symptoms of heart failure
  • Liver problems
  • Recent operation
  • Fever
  • Shock
  • Severe vomiting
  • Severe diarrhea
  • Serious lack of oxygen in the blood
  • Weakened patient
  • Injury
  • Sepsis syndrome
  • X-Ray Study with intravenous iodine contrast agent
  • Kidney disease with a likely reduction in kidney function
  • Acute inflammation of the pancreas
  • Chronic inflammation of the pancreas
  • Moderate to Severe kidney impairment
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Dosage of Canagliflozin

Strengths: 100 mg; 300 mg

Diabetes Type 2

  • Initial dose: 100 mg orally once a day
  • May increase to 300 mg orally once a day for additional glycemic control but only in patients who have tolerated lower dose and who have an eGFR of 60 mL/min/1.73 m2 or greater
  • Maximum dose: 300 mg/day

Side Effects of Canagliflozin

Most common

More common

Less common

  • Abnormal stools
  • bad, unusual, or unpleasant (after) taste
  • change in taste
  • difficulty with moving
  • discoloration of the fingernails or toenails
  • flu-like symptoms
  • joint pain
  • rash
  • a runny nose
  • sneezing
  • stuffy nose
  • swollen joints

Drug Interactions of Canagliflozin

Canagliflozin may interact with following drugs, supplements & may decrease the efficacy of the drug

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Pregnancy & Lactation of Canagliflozin

FDA Pregnancy Category B

Pregnancy

This medication should not be used during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding

It is not known if canagliflozin passes into breast milk. Metformin passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Breast-feeding is not recommended when you are taking this medication.

References

 

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