Description

Simple

A medication used to lower blood glucose levels in patients with type 2 diabetes.

Clinical

A sodium-glucose co-transporter 2 (SGLT2) inhibitor used to manage hyperglycemia in type 2 diabetes mellitus (DM). Also used to reduce the risk of major cardiovascular events in patients with established cardiovascular disease and type 2 DM.

Overview

Canagliflozin, also known as _Invokana_, is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used in the management of type 2 diabetes mellitus along with lifestyle changes including diet and exercise [FDA label].

It was initially approved by the FDA in 2013 for the management of diabetes and later approved in 2018 for a second indication of reducing the risk of cardiovascular events in patients diagnosed with type 2 diabetes mellitus [8], [FDA label].

Canagliflozin is the first oral antidiabetic drug approved for the prevention of cardiovascular events in patients with type 2 diabetes [8]. Cardiovascular disease is the most common cause of death in these patients [4].

Pharmacology

Indication

This drug is used in conjunction with diet and exercise to increase glycemic control in adults diagnosed with type 2 diabetes mellitus [FDA label].

Another indication for canagliflozin is the prevention of major cardiovascular events (myocardial infarction, stroke, or death due to a cardiovascula... Read more

Pharmacodynamic

This drug increases urinary glucose excretion and decreases the renal threshold for glucose (RTG) in a dose-dependent manner [FDA label]. The renal threshold is defined as the lowest level of blood glucose associated with the appearance of detectable glucose in the urine [ Read more

Mechanism of action

The sodium-glucose co-transporter2 (SGLT2), is found in the proximal tubules of the kidney, and reabsorbs filtered glucose from the renal tubular lumen. Canagliflozin inhibits the SGLT2 co-transporter. This inhibition leads to lower reabsorption of filtered glucose into the body and decreases the re... Read more

Absorption

**Bioavailability and steady-state**

The absolute oral bioavailability of canagliflozin, on average, is approximately 65% [FDA label]. Steady-state concentrations are achieved after 4 to 5 days of daily dose administration between the range of 100mg to 300mg [FDA label].

**Effect of food on a... Read more

Protein binding

Canagliflozin is mainly bound to albumin. The plasma protein binding of this drug is 99% [FDA label].

Volume of distribution

This drug is extensively distributed throughout the body. On average, the volume of distribution of canagliflozin at steady state following a single intravenous dose in healthy patients was measured to be 83.5 L [FDA label].

Clearance

In healthy subjects, canagliflozin clearance was approximately 192 mL/min after intravenous (IV) administration [FDA Label].The renal clearance of 100 mg and 300 mg doses of canagliflozin was measured to be in the range of 1.30 - 1.55 mL/min [FDA label].

Half life

In a clinical study, the terminal half-life of canagliflozin was 10.6 hours for the 100mg dose and 13.1 hours for the 300 mg dose [FDA label].

Route of elimination

After a single oral radiolabeled dose canagliflozin dose to healthy subjects, the following ratios of canagliflozin or metabolites were measured in the feces and urine [FDA label]:

**Feces**

41.5% as the unchanged radiolabeled drug

7.0% as a hydroxylated metabolite

3.2% as an O-glucuroni... Read more

Toxicity

**Overdose information**

If an overdose occurs, contact the Poison Control Center. Normal supportive measures should be taken, including the removal unabsorbed drug from the gastrointestinal tract, initiating clinical monitoring of the patient, and providing supportive treatment as deemed necessa... Read more

Adverse Effects

Contraindications

  • Regions: US
  • Patient Conditions:
      • Name: Diabetes, Type 1
      • Drugbank Id: DBCOND0034482
      • Combination Of:
        • Additional Characteristics:
          • Insulin-Dependent
        • Included Conditions:
            • Name: Diabetes Mellitus
            • Drugbank Id: DBCOND0027886
  • Regions: Canada
  • Patient Conditions:
      • Name: History of diabetic ketoacidosis (DKA)
      • Drugbank Id: DBCOND0118946
  • Regions: Canada
  • Patient Conditions:
      • Name: Diabetic Ketoacidosis
      • Drugbank Id: DBCOND0000979
  • Regions: US
  • Patient Conditions:
      • Name: Severe drug hypersensitivity reaction
      • Drugbank Id: DBCOND0099526
      • Modification Of:
        • Base:
          • Name: Drug hypersensitivity reaction
          • Drugbank Id: DBCOND0022247
        • Severity:
          • Includes:
            • severe
  • Regions: US
  • Patient Conditions:
      • Name: Patients on Dialysis
      • Drugbank Id: DBCOND0085975
      • Name: Severe Renal Impairment
      • Drugbank Id: DBCOND0045819
      • Modification Of:
        • Base:
          • Name: Renal Impairment
          • Drugbank Id: DBCOND0031781
        • Severity:
          • Includes:
            • severe
      • Name: End Stage Renal Disease
      • Drugbank Id: DBCOND0028894
  • Regions: US
  • Patient Conditions:
      • Name: Patients with an eGFR less than 30 mL/min/1.73 m2 caused by End Stage Renal Disease, Severe Renal Impairment, Moderate Renal Impairment
      • Drugbank Id: DBCOND0118944
      • Combination Of:
        • Caused By:
            • Name: Moderate Renal Impairment
            • Drugbank Id: DBCOND0069838
            • Name: End Stage Renal Disease
            • Drugbank Id: DBCOND0028894
            • Name: Severe Renal Impairment
            • Drugbank Id: DBCOND0045819
        • Included Conditions:
            • Name: Patients with an eGFR less than 30 mL/min/1.73 m2
            • Drugbank Id: DBCOND0118945

Food Interactions

  • Avoid alcohol. Excess alcohol intake may promote ketoacidosis.
  • Drink plenty of fluids.
  • Take before a meal. It is recommended to take this drug before the first meal of the day.

Interactions

Type in a drug name to check for interaction with Canagliflozin
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
2,4-thiazolidinedione
Canagliflozin may increase the hypoglycemic activities of 2,4-thiazolidinedione.
5-(2-methylpiperazine-1-sulfonyl)isoquinoline
The therapeutic efficacy of Canagliflozin can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the orthostatic hypotensive activities of Canagliflozin.
Abacavir
Canagliflozin may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
Acarbose
Canagliflozin may increase the hypoglycemic activities of Acarbose.
Acebutolol
The therapeutic efficacy of Acebutolol can be increased when used in combination with Canagliflozin.
Aceclofenac
Aceclofenac may decrease the excretion rate of Canagliflozin which could result in a higher serum level.
Acemetacin
The therapeutic efficacy of Canagliflozin can be decreased when used in combination with Acemetacin.
Acetaminophen
Canagliflozin may increase the excretion rate of Acetaminophen which could result in a lower serum level and potentially a reduction in efficacy.
Acetazolamide
The therapeutic efficacy of Canagliflozin can be increased when used in combination with Acetazolamide.
Acetohexamide
Canagliflozin may increase the hypoglycemic activities of Acetohexamide.
Acetyl sulfisoxazole
The therapeutic efficacy of Canagliflozin can be increased when used in combination with Acetyl sulfisoxazole.
Acetyldigoxin
Canagliflozin may decrease the excretion rate of Acetyldigoxin which could result in a higher serum level.
Acetylsalicylic acid
The risk or severity of hypoglycemia can be increased when Acetylsalicylic acid is combined with Canagliflozin.
Aclidinium
Canagliflozin may increase the excretion rate of Aclidinium which could result in a lower serum level and potentially a reduction in efficacy.
Acrivastine
Canagliflozin may increase the excretion rate of Acrivastine which could result in a lower serum level and potentially a reduction in efficacy.
Acyclovir
Acyclovir may decrease the excretion rate of Canagliflozin which could result in a higher serum level.
Adefovir
Adefovir may decrease the excretion rate of Canagliflozin which could result in a higher serum level.
Adefovir dipivoxil
Adefovir dipivoxil may decrease the excretion rate of Canagliflozin which could result in a higher serum level.
Afatinib
The serum concentration of Afatinib can be increased when it is combined with Canagliflozin.
11 References
  1. 1 . Lamos EM, Younk LM, Davis SN: Canagliflozin , an inhibitor of sodium-glucose cotransporter 2, for the treatment of type 2 diabetes mellitus. Expert Opin Drug Metab Toxicol. 2013 Jun;9(6):763-75. doi: 10.1517/17425255.2013.791282. Epub 2013 Apr 17.PubMed: 23590413
  2. 2 . Osaki A, Okada S, Saito T, Yamada E, Ono K, Niijima Y, Hoshi H, Yamada M: Renal threshold for glucose reabsorption predicts diabetes improvement by sodium-glucose cotransporter 2 inhibitor therapy. J Diabetes Investig. 2016 Sep;7(5):751-4. doi: 10.1111/jdi.12473. Epub 2016 Feb 16.PubMed: 27181936
  3. 3 . Deeks ED, Scheen AJ: Canagliflozin: A Review in Type 2 Diabetes. Drugs. 2017 Sep;77(14):1577-1592. doi: 10.1007/s40265-017-0801-6.PubMed: 28836175
  4. 4 . Joseph JJ, Golden SH: Type 2 diabetes and cardiovascular disease: what next? Curr Opin Endocrinol Diabetes Obes. 2014 Apr;21(2):109-20. doi: 10.1097/MED.0000000000000044.PubMed: 24569552
  5. 5 . Gleissner CA, Galkina E, Nadler JL, Ley K: Mechanisms by which diabetes increases cardiovascular disease. Drug Discov Today Dis Mech. 2007;4(3):131-140. doi: 10.1016/j.ddmec.2007.12.005.PubMed: 18695749
  6. 6 . Mannucci E, Dicembrini I, Lauria A, Pozzilli P: Is glucose control important for prevention of cardiovascular disease in diabetes? Diabetes Care. 2013 Aug;36 Suppl 2:S259-63. doi: 10.2337/dcS13-2018.PubMed: 23882055
  7. 7 . Steven L. Cowart and Max E. Stachura (1990). Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. (3rd ed.). Butterworths.
  8. 8 . U.S. FDA Approves INVOKANA® (canagliflozin) to Reduce the Risk of Heart Attack, Stroke or Cardiovascular Death in Adults with Type 2 Diabetes and Established Cardiovascular Disease Link
  9. 9 . Diabetes, Heart Disease, and Stroke: NIDDK Link
  10. 10 . FDA Approved Drug Products: Invokana (canagliflozin) oral tablets Link
  11. 11 . Invokana, Canadian monograph File