Pharm
Canagliflozin
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Canagliflozin
, Invokana
See Also
SGLT2 Inhibitor
Type II Diabetes Medications
Dapagliflozin
Empagliflozin
Ertugliflozin
Sotagliflozin
Bexagliflozin
Indications
Type 2 Diabetes Mellitus
Management
Comorbid
Chronic Kidney Disease
or
Microalbuminuria
Comorbid
Congestive Heart Failure
Like
GLP-1 Agonist
s,
SGLT2 Inhibitor
s have moved to first-line agents for their effects on conditions comorbid to Diabetes
SGLT2 Inhibitor
s (as with
GLP-1 Agonist
s) may assist with weight loss in
Obesity
SGLT2 Inhibitor
s (as with
GLP-1 Agonist
s) decrease
Cardiovascular Risk
Best evidence for
Empagliflozin
(
Jardiance
)
SGLT2 Inhibitor
s (as with
GLP-1 Agonist
s) decrease
Chronic Kidney Disease
progression
Best evidence for
Empagliflozin
(
Jardiance
), Canagliflozin (Invokana),
Dapagliflozin
(
Farxiga
)
Contraindications
Type 1 Diabetes Mellitus
Renal dysfunction: GFR <30 ml/min
Originally not recommended if GFR <45 ml/min
Other relative contraindications (use with caution)
Diabetic Ketoacidosis
(relative contraindication)
Osteoporosis
or
Osteopenia
(low
Bone Mineral Density
)
Diabetic Foot Wound
(
Neuropathic Foot Ulcer
)
Perioperative status (or prolonged
Fastin
g,
Dehydration
)
Hold for at least 3 to 4 days before major surgery
Mechanism
Sodium-Glucose Transporter 2
(SGLT2)
SGLT2 acts in the
Kidney
s to resorb
Glucose
at the proximal tubules
SGLT2 mediates 90% of renal
Glucose
reabsorption from the tubules
SGLT2 Inhibitor
s
Blocks SGLT2, Allowing more
Glucose
to remain in the urine without reabsorption
Results in osmotic diuresis
Efficacy is lower when GFR is decreased
Medications
Canagliflozin (Invokana)
Dosing
AM dosing is recommended due to
Diuretic
effect
Taken 30 minutes before first meal of day
Avoid in
Dehydration
Start: 100 mg orally daily
Maximum: 300 mg orally daily
Avoid 300 mg dose if GFR <60 ml/min
Pharmacokinetics
See
SGLT2 Inhibitor
SGLT2 Inhibitor
s share similar
Pharmacokinetics
Rapid absorption and peak activity within 1-2 hours
Half-Life
10 hours (100 mg dose) to 13 hours (300 mg dose)
Efficacy
Class Effects
Lower efficacy in moderate to severe renal
Impairment
May lower
Blood Pressure
by 3-5 mmHg (via similar mechanism to weight)
May lower weight up to 4 to 7 pounds (via diuresis)
Decrease
Cardiovascular Risk
Decrease
Chronic Kidney Disease
progression
Lowers
Hemoglobin A1C
0.5 to 1%
Glucose
lowering effect decreases with lower GFR
Low risk of
Hypoglycemia
Invokana (Canagliflozin) specific effects
Delays
Chronic Kidney Disease
progression (likely a class effect)
When taken for 2.5 years, delays
Serum Creatinine
doubling in those with GFR <60 ml/min (NNT 31)
Balance with the risk of
Acute Kidney Injury
in those dehydrated while taking
SGLT2 Inhibitor
s
Perkovic (2019) N Engl J Med +PMID: 30990260 [PubMed]
Adverse Effects
Perioperative Recommendations
See
Preoperative Guidelines for Medications Prior to Surgery
Stop
SGLT2 Inhibitor
s 3 days before surgery (due to
Euglycemic Ketoacidosis
risk)
Restart
SGLT2 Inhibitor
s post-operatively when oral intake returns to normal
Urinary Tract Infection
Genital yeast infection
Number needed to harm (NNH) 17 in women, 40 in men
Fournier's Gangrene
https://www.fda.gov/Drugs/DrugSafety/ucm617360.htm
Euglycemic Ketoacidosis
See
Euglycemic Ketoacidosis
Presents with
Anion Gap Metabolic Acidosis
(
Ketoacidosis
despite normal
Serum Glucose
)
Diuretic
effect
Risk of
Dehydration
,
Orthostatic Hypotension
Risk of
Acute Kidney Injury
(see below)
Acute Kidney Injury
Seen with Canagliflozin (Invokana) and
Dapagliflozin
(
Farxiga
), but likely a class effect due to diuresis
Higher risk when combined with
ACE Inhibitor
s (and ARBs),
NSAID
s and
Diuretic
s and esp. in elderly
Avoid
Hypovolemia
, and consider lowering
Diuretic
dose when on
SGLT2 Inhibitor
Check
Serum Creatinine
before initiating agent, 10-14 days later and again with dose increase
Stop and hold the SGLT2 Inhibitor
Serum Creatinine
rises >30%
http://www.fda.gov/Drugs/DrugSafety/ucm505860.htm
Hyperkalemia
When used in combination with
ACE Inhibitor
s,
Angiotensin Receptor Blocker
s or
Potassium
Sparing
Diuretic
s
May also decrease
Serum Potassium
LDL Cholesterol
increase (4-8 mg/dl)
Bladder Cancer
increased risk
Associated only with
Farxiga
Fracture
s
Upper extremity
Fracture
s most common (and not caused by major
Trauma
)
Number needed to harm 125 for one additional
Fracture
with Invokana over 18 months of use
Invokana and for those with
Renal Insufficiency
,
Farxiga
, have been associated with increased risk
Unknown mechanism (possibly decreased
Bone Mineral Density
, increased
Fall Risk
)
http://www.fda.gov/Drugs/DrugSafety/ucm461449.htm
Acute Pancreatitis
Amputation Risk
Canagliflozin associated with increased risk of amputations
Relative Risk
: 2.0 (risk of 6 amputations per 1000 on Canagliflozin)
May be a
SGLT2 Inhibitor
class effect (unclear mechanism)
See
Amputation Prevention in Diabetes Mellitus
FDA Drug Safety Communication
https://www.fda.gov/Drugs/DrugSafety/ucm557507.htm
Safety
Avoid in
Lactation
Pregnancy
Unknown safety in first trimester
Avoid in second and third trimester
Monitoring
Renal Function
Resources
Canagliflozin (DailyMed)
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b9057d3b-b104-4f09-8a61-c61ef9d4a3f3
Efficacy and safety of Canagliflozin
http://onlinelibrary.wiley.com/doi/10.1111/dom.12054/pdf
Stenlöf (2013 )Diabetes Obes Metab 15(4):372-82 +PMID: 23279307 [PubMed]
References
(2020) Presc Lett 27(12): 68
(2020) Presc Lett 27(5): 26
(2018) Presc Lett 25(2)
(2016) Presc Lett 23(2): 8-9
(2014) Presc Lett 21(10): 57
(2013) Presc Lett 20(5): 28
Tomaszewski (2022) Crit Dec Emerg Med 36(11): 32
Nisly (2013)Am J Health-Syst Pharm 70 (4):311-9 [PubMed]
Stenlof (2013) Diabetes Obes Metab 15(4): 372-82 [PubMed]
Vaughan (2024) Am Fam Physician 109(4): 333-42 [PubMed]
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