Appendix 6

*2015 UPDATE* This appendix has been updated. Please click here to view the most current version of Appendix 6.

Therapeutic Considerations for Renal Impairment

Part A:

Therapeutic considerations when using common therapies in patients with diabetes with varying degrees of renal impairment
Antihyperglycemic Therapies
  CKD 1 & 2 eGFR ≥60 mL/min CKD 3 eGFR 30-59 mL/min CKD 4 eGFR 15-29 mL/min CKD 5 eGFR <15 mL/min or dialysis Comments
Metformin No dose adjustment Reduce dose Use alternative agent See “Sick Day Medication List” (Appendix 7).Risk of drug accumulation with declining renal function, especially if acute.
Alpha-glucosidase Inhibitor
Acarbose No dose adjustment No dose adjustment Use alternative agent  
DPP4-Inhibitors
Linagliptin No dose adjustment required Experience in patients with ESRD or on dialysis is limited. Use with caution in these patients.
Saxagliptin   Lower Dose 2.5 mg once daily (<50 mL/min) Use alternative agent Should not be used in patients on dialysis.
Sitagliptin   Lower dose (50 mg daily) (30-49 mL/min) Use lowest dose (25 mg daily) Risk of accumulation.
GLP-1 Receptor Agonists
Exenatide No dose adjustment Lower dose (5 mcg BID) Use alternative agent  
Liraglutide No dose adjustment Use alternative agent (<50 mL/min)  
Insulin Secretagogues
Gliclazide     Risk of hypoglyce- mia, consider lower dose Risk of hypoglyce- mia, consider alternative agent  
Glimepiride     Risk of hypoglyce- mia, consider lower dose Max 1 mg daily, consider alternative agent Both pharmacokinetics and pharmacodynamics are altered, increasing risk of hypoglycemia.
Glyburide   Use alternative agent Increased risk of prolonged hypoglycemia due to accumulation of parent drug and active metabolites.
Nateglinide No dose adjustment required  
Repaglinide No dose adjustment required  
Thiazolidinediones (TZDs)
Pioglita- zone No dose adjustment required Risk of volume overload.
Rosiglita- zone No dose adjustment required Risk of volume overload.

Part B:

Lipid Lowering Therapies
Bile Acid Sequestrant
Cholestyra- mine No dose adjustment  
Cholesterol Absorption Inhibitor
Ezetimibe No dose adjustment  
Nicotinic Acid
(niacin)
No dose
adjustment
50% of total daily dose administered as divided doses 25% of total daily dose administered in divided doses  
Fibrates Risk of rhabdomyolisis when fibrates used in combination with statins is increased in CKD and, therefore, combination should be avoided.
Bezafibrate No dose adjustment Use alternative agent  
Fenofibrate No dose adjustment Reduce dose Use alternative agent Fenofibrate micronized should not be used as initial treatment in CKD. Initiate with Lipidil EZ 48 mg/day.
Gemfibrozil No dose adjustment Use alternative agent Concomitant use of gemfibrozil and repaglinide should be avoided as can result in hypoglycemia.
Statins
Atorvastatin   Manufacturer recommends lowest dose (10 mg once daily) be used Plasma concentrations are similar to those with normal renal function, but several cases of rhabdomyolysis reported in patients with renal insufficiency.
Fluvastatin No dose adjustment Not recommended Recommendation from manufacturer is based on lack of experience rather than renal excretion.
Lovastatin No dose adjustment Use low dose (max dose 20 mg/day) 10% renal elimination. Doubling of plasma concentration in moderate to severe renal impairment.
Pravastatin   Use lowest dose as precautionary measure Lack of data. 20% renal elimination.
Rosuva- statin No dose adjustment Use low dose (max dose 10 mg/day) 10% renal elimination.
Simvastatin No dose adjustment Use low dose (max dose 10 mg/day) 13% renal elimination.
Neuropathy Therapies
Anticonvulsants
Gabapentin Max 3600 mg/day divided tid Max 1400 mg/day divided bid Max 700 mg/day given once daily Max 150-300 mg/day given once daily Hemodialysis supplemental dosing required: 125-350 mg after each 4 hours of hemodialysis.
Pregabalin Max 600 mg/day divided bid or tid Max 300 mg/day divided bid or tid Max 150 mg/day given once daily or bid Max 75 mg/day given once daily Hemodialysis supplemental dosing required.
Erectile Dysfunction Therapies
Phosphodiesterase-5 (PDE-5) Inhibitors
Sildenafil No dose adjustment Reduce starting dose to 25 mg  
Tadalafil   10-20 mg (max frequency of alternate days and not more than 3 times per week) 2.5-5 mg once a day may be considered in CKD stage 3 but daily dosing is not recommended in CKD stage 4 and 5.

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