SGLT2 INHIBITOR DOSING

• ACRONYMS AND DEFINITIONS

• CHF - Congestive heart failure
• CV - Cardiovascular
• CVD - Cardiovascular disease
• GFR - Glomerular filtration rate
• HFrEF - Heart failure with reduced ejection fraction
• Met - metformin
• SGLT2 - Sodium-glucose co-transporter
• T2DM - Type 2 diabetes

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• Kidney disease dosing
• Canagliflozin (Invokana®)
• GFR 45 - 59 ml/min: Dose should not exceed 100 mg a day
• GFR < 45 ml/min: DO NOT USE


• Dapagliflozin (Farxiga®)
• See dapagliflozin dosing above


• Empagliflozin (Jardiance®)
• Type 2 diabetes
• GFR ≥ 30 ml/min: no dose adjustment necessary
• GFR < 30 ml/min: not recommended. Likely to be ineffective for glucose control.
• Heart failure with reduced EF
• GFR ≥ 20 ml/min: no dose adjustment necessary
• GFR < 20 ml/min: has not been studied. Not recommended.


• Ertugliflozin (Steglatro™)
• GFR ≥ 45 ml/min: no dose adjustment necessary
• GFR < 45 ml/min: not recommended. Do not use in patients on dialysis.

• Liver disease dosing
• Canagliflozin (Invokana®)
• Mild-to-moderate liver disease (Child-Pugh class A and B): No dosage adjustment is necessary
• Severe liver disease (Child-Pugh class C): Has not been studied. Do not use.


• Dapagliflozin (Farxiga®)
• No dose adjustment is necessary in mild, moderate, or severe liver disease
• Has not been studied extensively in patients with severe liver disease


• Empagliflozin (Jardiance®)
• No dose adjustment necessary [7]


• Ertugliflozin (Steglatro™)
• Mild-to-moderate liver disease (Child-Pugh class A and B): No dosage adjustment is necessary
• Severe liver disease (Child-Pugh class C): Has not been studied. Not recommended.

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• DRUG INTERACTIONS

• NOTE: The drug interactions presented here are NOT all-inclusive. Other interactions may exist. Drug interaction checkers provide the most efficient and practical way to check for interactions among multiple medications. A free interaction checker is available from Drugs.com (see Drugs.com interactions checker).


• All SGLT2 inhibitors
• Diuretics - SGLT2 inhibitors may potentiate the diuresis that occurs with diuretics. This may result in increased urination and volume depletion. Monitor patients for signs of dehydration when prescribing together. Diuretics include thiazide diuretics, loop diuretics, and aldosterone antagonists.
• Insulin and insulin secretagogues - the risk of hypoglycemia is increased when SGLT2 inhibitors are prescribed with insulin and insulin secretagogues (e.g. sulfonylureas, meglitinides). Monitor blood sugars closely when combining, particularly during initiation and dose changes.
• Lithium - SGLT2 inhibitors may reduce serum lithium concentrations. Monitor lithium levels closely during SGLT2 inhibitor initiation and dosage changes.


• Canagliflozin (Invokana™)
• Drugs that raise potassium levels
• Canagliflozin has the potential to raise potassium levels. This effect appears to be more pronounced with the 300 mg dose.
• It may interact with other drugs that raise potassium causing hyperkalemia (high blood potassium levels)
• Drugs that may raise potassium levels include:
• Aldosterone antagonists (spironolactone, eplerenone)
• Aliskiren (Tekturna®)
• ARBs (losartan, valsartan, etc.)
• Cyclosporine (Neoral®)
• ENaC inhibitors (triamterene, amiloride)
• Penicillin G potassium injection (1 million units contains 1.68mEq of potassium)
• Potassium supplements (K-Dur®, etc.)
• Tacrolimus
• Trimethoprim (part of Bactrim® and Septra®)
• UGT enzyme inducers
• Canagliflozin is primarily metabolized through O-glucuronidation by UGT1A9 and UGT2B4. UGT inducers may decrease canagliflozin exposure and reduce its effectiveness. When prescribing UGT inducers (e.g. rifampin, phenytoin, phenobarbital, ritonavir) with canagliflozin, the following is recommended:
• CrCl ≥ 60 ml/min: for patients taking 100 mg/day, increase to 200 mg/day. For patients taking 200 mg/day, increase to 300 mg/day.
• CrCl < 60 ml/min: for patients taking 100 mg/day, increase to 200 mg/day
• Digoxin - Canagliflozin has the potential to raise digoxin levels. Monitor levels appropriately.

• Metabolism and clearance
• Canagliflozin (Invokana®)
• UGT1A9 - substrate
• UGT2B4 - substrate
• CYP3A4 - minor substrate
• Dapagliflozin (Farxiga®)
• UGT1A9 - major substrate
• OAT3 - substrate
• P-glycoprotein - weak substrate
• Cytochrome P450 metabolism - undefined, minor pathway
• Empagliflozin (Jardiance®)
• UGT2B7, UGT1A3, UGT1A8, and UGT1A9 - substrate
• OAT3 - substrate
• OATP1B1 and OATP1B3 - substrate
• P-glycoprotein - substrate
• BCRP - substrate
• Ertugliflozin (Steglatro™)
• UGT2B7 and UGT1A9 - substrate
• UGT1A1 and UGT1A4 - weak inhibitor
• P-glycoprotein - substrate
• BCRP - substrate

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• PRICE ($) INFO

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• BIBLIOGRAPHY

• 1 - Canagliflozin PI
• 2 - Dapagliflozin PI
• 3 - Empagliflozin PI
• 4 - Ertugliflozin PI