Canagliflozin

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Canagliflozin Brand Name– Invokana

What is Canagliflozin

Canagliflozin is an oral sodium-glucose co-transporter 2 (SGLT2) inhibitor. Canagliflozin works by blocking the reabsorption of glucose by the kidney, which results in increased glucose excretion and reduced blood glucose concentrations.

Canagliflozin is used to improve glycemic control in adults with type 2 diabetes mellitus (DM) and to reduce the risk of cardiovascular (CV) death in type 2 DM patients who also have CV disease.

Canagliflozin is also used to reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, CV death, and hospitalization for heart failure (HF) in adults with type 2 DM and diabetic nephropathy with albuminuria.

Mean A1C reductions of 0.77% to 1.03% are achieved with use. Canagliflozin has been shown to reduce CV risk and HF risk in clinical trials.

Canagliflozin significantly reduced the risk of major adverse CV events (MACE: CV death, the first occurrence of non-fatal myocardial infarction, or non-fatal stroke) by 14% relative to placebo (HR 0.86, 95% CI 0.75 to 0.97) in patients with type 2 DM and established, stable, atherosclerotic CV disease.

In the CREDENCE trial, the risk of the primary composite outcome of ESKD, doubling of serum creatinine, or death from renal or CV causes was 30% lower with canagliflozin treatment when compared with placebo.

Canagliflozin is contraindicated for use in patients with severe renal impairment who are being treated for glycemic control and in patients on dialysis.

There is a boxed warning regarding risk for amputation in the product label; in adult patients with type 2 DM who have established CV disease or who are at risk for CV disease, canagliflozin has been associated with lower-limb amputations, most frequently of the toe and midfoot; some also involved the leg.

Metformin is first-line in the treatment of type 2 DM. Additional therapy with an SGLT2 inhibitor with evidence of reducing HF and/or chronic kidney disease (CKD) progression should be considered in patients with indicators of high-risk or established CKD or HF, independent of baseline A1C or individualized A1C target.

SGLT2 inhibitors with proven CV-risk reduction, like canagliflozin, are also an alternative treatment option in DM patients with indicators of high-risk or established CV disease who cannot tolerate a glucagon-like peptide-1 receptor agonist (GLP-1 RA).

Indications

  1. diabetic nephropathy
  2. reduction of cardiovascular mortality
  3. reduction of heart failure hospitalizations
  4. type 2 diabetes mellitus

For the treatment of type 2 diabetes mellitus (T2DM) in combination with diet and exercise

Side Effects

  1. abdominal pain
  2. anaphylactoid reactions
  3. angioedema
  4. asthenia
  5. balanitis
  6. bone fractures
  7. candidiasis
  8. constipation
  9. cystitis
  10. dehydration
  11. diabetic ketoacidosis
  12. diuresis
  13. dizziness
  14. erythema multiforme
  15. fatigue
  16. hypercholesterolemia
  17. hyperkalemia
  18. hyperlipidemia
  19. hypermagnesemia
  20. hyperphosphatemia
  21. hypoglycemia
  22. hypotension
  23. increased urinary frequency
  24. infection
  25. lower limb amputation
  26. nausea
  27. necrotizing fasciitis
  28. new primary malignancy
  29. nocturia
  30. osteopenia
  31. pancreatitis
  32. phimosis
  33. photosensitivity
  34. polydipsia
  35. polyuria
  36. pruritus
  37. rash
  38. renal failure (unspecified)
  39. syncope
  40. tissue necrosis
  41. urinary urgency
  42. urticaria
  43. vaginitis
  44. xerostomia

Monitoring Parameters

  • blood glucose
  • glycosylated hemoglobin A1c (HbA1c)
  • serum cholesterol profile
  • serum creatinine/BUN
  • serum electrolytes

Contraindications

  • adrenal insufficiency
  • balanitis
  • bone fractures
  • breast-feeding
  • children
  • dehydration
  • diabetic ketoacidosis
  • dialysis
  • fever
  • geriatric
  • hepatic disease
  • hypercholesterolemia
  • hypercortisolism
  • hyperglycemia
  • hyperthyroidism
  • hypoglycemia
  • hypotension
  • hypothyroidism
  • hypovolemia
  • infants
  • infection
  • laboratory test interference
  • lower limb amputation
  • malnutrition
  • osteopenia
  • osteoporosis
  • peripheral neuropathy
  • peripheral vascular disease
  • pituitary insufficiency
  • pregnancy
  • pyelonephritis
  • renal disease
  • renal failure
  • renal impairment
  • surgery
  • tissue necrosis
  • type 1 diabetes mellitus
  • urinary tract infection (UTI)
  • vaginitis

Interactions

  • Acebutolol
  • Acetaminophen; Aspirin, ASA; Caffeine
  • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
  • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
  • Acetazolamide
  • Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
  • Aliskiren; Hydrochlorothiazide, HCTZ
  • Aliskiren; Valsartan
  • Amiloride
  • Amiloride; Hydrochlorothiazide, HCTZ
  • Aminosalicylate sodium, Aminosalicylic acid
  • Amlodipine; Benazepril
  • Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan
  • Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
  • Amlodipine; Olmesartan
  • Amlodipine; Telmisartan
  • Amlodipine; Valsartan
  • Amoxicillin; Clarithromycin; Lansoprazole
  • Amoxicillin; Clarithromycin; Omeprazole
  • Amprenavir
  • Androgens
  • Angiotensin II receptor antagonists
  • Angiotensin-converting enzyme inhibitors
  • Apalutamide
  • Aspirin, ASA
  • Aspirin, ASA; Butalbital; Caffeine
  • Aspirin, ASA; Butalbital; Caffeine; Codeine
  • Aspirin, ASA; Caffeine; Dihydrocodeine
  • Aspirin, ASA; Caffeine; Orphenadrine
  • Aspirin, ASA; Carisoprodol
  • Aspirin, ASA; Carisoprodol; Codeine
  • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
  • Aspirin, ASA; Dipyridamole
  • Aspirin, ASA; Omeprazole
  • Aspirin, ASA; Oxycodone
  • Aspirin, ASA; Pravastatin
  • Atazanavir
  • Atazanavir; Cobicistat
  • Atenolol
  • Atenolol; Chlorthalidone
  • Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
  • Atropine; Hyoscyamine; Phenobarbital; Scopolamine
  • atypical antipsychotic
  • Azilsartan
  • Azilsartan; Chlorthalidone
  • Belladonna Alkaloids; Ergotamine; Phenobarbital
  • Benazepril
  • Benazepril; Hydrochlorothiazide, HCTZ
  • Bendroflumethiazide; Nadolol
  • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
  • Beta-blockers
  • Betaxolol
  • Bismuth Subsalicylate
  • Bismuth Subsalicylate; Metronidazole; Tetracycline
  • Bisoprolol
  • Bisoprolol; Hydrochlorothiazide, HCTZ
  • Bortezomib
  • Brimonidine; Timolol
  • Bumetanide
  • Candesartan
  • Candesartan; Hydrochlorothiazide, HCTZ
  • Captopril
  • Captopril; Hydrochlorothiazide, HCTZ
  • Carbonic anhydrase inhibitors
  • Carteolol
  • Carvedilol
  • Chloroquine
  • Chlorothiazide
  • Chlorthalidone
  • Chlorthalidone; Clonidine
  • Choline Salicylate; Magnesium Salicylate
  • Chromium
  • Clarithromycin
  • Clonidine
  • Corticosteroids
  • Daclatasvir
  • Darunavir
  • Darunavir; Cobicistat
  • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
  • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
  • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
  • Diazoxide
  • Digoxin
  • Dorzolamide; Timolol
  • Elbasvir; Grazoprevir
  • Enalapril, Enalaprilat
  • Enalapril; Felodipine
  • Enalapril; Hydrochlorothiazide, HCTZ
  • Eprosartan
  • Eprosartan; Hydrochlorothiazide, HCTZ
  • Esmolol
  • Estrogens
  • Ethacrynic Acid
  • Ethanol
  • Ethotoin
  • Fibric acid derivatives
  • Fluoxetine
  • Fluoxetine; Olanzapine
  • Fosamprenavir
  • Fosinopril
  • Fosinopril; Hydrochlorothiazide, HCTZ
  • Fosphenytoin
  • Furosemide
  • Garlic, Allium sativum
  • Glecaprevir; Pibrentasvir
  • Green Tea
  • Hydralazine; Hydrochlorothiazide, HCTZ
  • Hydrochlorothiazide, HCTZ
  • Hydrochlorothiazide, HCTZ; Irbesartan
  • Hydrochlorothiazide, HCTZ; Lisinopril
  • Hydrochlorothiazide, HCTZ; Losartan
  • Hydrochlorothiazide, HCTZ; Methyldopa
  • Hydrochlorothiazide, HCTZ; Metoprolol
  • Hydrochlorothiazide, HCTZ; Moexipril
  • Hydrochlorothiazide, HCTZ; Olmesartan
  • Hydrochlorothiazide, HCTZ; Propranolol
  • Hydrochlorothiazide, HCTZ; Quinapril
  • Hydrochlorothiazide, HCTZ; Spironolactone
  • Hydrochlorothiazide, HCTZ; Telmisartan
  • Hydrochlorothiazide, HCTZ; Triamterene
  • Hydrochlorothiazide, HCTZ; Valsartan
  • Hydroxychloroquine
  • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
  • Indinavir
  • Irbesartan
  • Isocarboxazid
  • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
  • Isoniazid, INH; Rifampin
  • Labetalol
  • Lanreotide
  • Ledipasvir; Sofosbuvir
  • Levobetaxolol
  • Levobunolol
  • Levothyroxine
  • Levothyroxine; Liothyronine (Porcine)
  • Levothyroxine; Liothyronine (Synthetic)
  • Liothyronine
  • Lisinopril
  • Lithium
  • Lomefloxacin
  • Loop diuretics
  • Lopinavir; Ritonavir
  • Losartan
  • Lovastatin; Niacin
  • Magnesium Salicylate
  • Mecasermin rinfabate
  • Mecasermin, Recombinant, rh-IGF-1
  • Methazolamide
  • Methyclothiazide
  • Metolazone
  • Metoprolol
  • Moexipril
  • Monoamine oxidase inhibitors
  • Nadolol
  • Nebivolol
  • Nebivolol; Valsartan
  • Nelfinavir
  • Niacin, Niacinamide
  • Niacin; Simvastatin
  • Nicotine
  • Octreotide
  • Olmesartan
  • Ombitasvir; Paritaprevir; Ritonavir
  • Orlistat
  • Pasireotide
  • Pegvisomant
  • Penbutolol
  • Pentamidine
  • Perindopril
  • Perindopril; Amlodipine
  • Phenelzine
  • Phenobarbital
  • Phenothiazines
  • Phenytoin
  • Pindolol
  • Potassium-sparing diuretics
  • Propranolol
  • Quinapril
  • Quinolones
  • Ramipril
  • Reserpine
  • Rifampin
  • Ritonavir
  • Sacubitril; Valsartan
  • Salicylates
  • Salsalate
  • Saquinavir
  • Selegiline
  • Sofosbuvir
  • Sofosbuvir; Velpatasvir
  • Sofosbuvir; Velpatasvir; Voxilaprevir
  • Somatropin, rh-GH
  • Sotalol
  • Sparfloxacin
  • Spironolactone
  • Sulfonamides
  • Sympathomimetics
  • Tacrolimus
  • Tegaserod
  • Telmisartan
  • Thiazide diuretics
  • Thyroid hormones
  • Timolol
  • Tipranavir
  • tobacco
  • Torsemide
  • Trandolapril
  • Trandolapril; Verapamil
  • Tranylcypromine
  • Triamterene
  • Trovafloxacin, Alatrofloxacin
  • Valsartan

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