Rhabdomyolysis and AKI with Atorvastatin and Sitagliptin Use in the Setting of Low 25-Hydroxyvitamin D Levels

Abstract

We report a case of an 86-year-old woman admitted to the hospital with rhabdomyolysis and acute kidney injury 3 weeks after starting sitagliptin while on long-term atorvastatin therapy. She also had low levels of 25-hydroxyvitamin D and mild chronic kidney disease, which may have contributed to the development of rhabdomyolysis. A review of the literature reveals four previous reports of this drug interaction in elderly patients, some with underlying kidney disease.

Sitagliptin and Simvastatin Interaction Causing Rhabdomyolysis and AKI

“…The sitagliptin package insert does not mention any drug interaction with statins [ 1 ]. A comprehensive literature review revealed six previous reports of rhabdomyolysis due to drug interaction between sitagliptin and statins including simvastatin, lovastatin, and atorvastatin [ 4 – 9 ] ( Table 1 ). Of these, only two cases had rhabdomyolysis-associated AKI neither of which were severe enough to require dialysis [ 4 , 6 ].…”

“…A comprehensive literature review revealed six previous reports of rhabdomyolysis due to drug interaction between sitagliptin and statins including simvastatin, lovastatin, and atorvastatin [ 4 – 9 ] ( Table 1 ). Of these, only two cases had rhabdomyolysis-associated AKI neither of which were severe enough to require dialysis [ 4 , 6 ]. The mechanisms proposed for this drug interaction include nephrotoxicity of sitagliptin causing reduced renal excretion of simvastatin and subsequently dose-related muscle breakdown.…”

“…The mechanisms proposed for this drug interaction include nephrotoxicity of sitagliptin causing reduced renal excretion of simvastatin and subsequently dose-related muscle breakdown. Other mechanisms suggest an interaction of statin and sitagliptin at the level of hepatic CYP3A4 as both are metabolized by the same enzyme and can potentially compete for it resulting in increased serum statin levels precipitating statin-induced rhabdomyolysis [ 4 , 5 ]. Only three of the reported seven cases so far had developed AKI, thus supporting the latter theory of drug interaction at the hepatic CYP3A4 level.…”

Rhabdomyolysis risk from the use of two‐drug combination of antidyslipidemic drugs with antihypertensive and antidiabetic medications: a signal detection analysis

“…Buttar et al. also report the occurrence of rhabdomyolysis following association of statins and DPP4 inhibitors.…”

“…The package insert of some angiotensin II receptor blockers, metformin, pioglitazone, and some dipeptidyl peptidase-IV (DPP4) inhibitors in Japan has a warning that these medications may cause rhabdomyolysis as a critical adverse drug reaction (ADR). Buttar et al [14] also report the occurrence of rhabdomyolysis following association of statins and DPP4 inhibitors.…”