P1113 - Risk of Atorvastatin Toxicity in Individuals With Hepatic Impairment

Karine Moussa, MD¹, Ashwini Mulgaonkar, MD², Adam Deising, MD², Jennifer Au, MD², Julio Gutierrez, MD^2
1Scripps Clinic, San Diego, CA; ²Scripps Clinic, La Jolla, CA

Introduction: Statins are generally considered safe in patients with chronic liver disease (CLD); however, caution should be exercised in those with impaired liver function. For example, Atorvastatin (ATV) is heavily CYP3A4 metabolized and its concentrations are also susceptible to drug-drug interactions, increasing the risk of dosage-dependent rhabdomyolysis.

Case Description/Methods: We searched amongst all patients listed for liver transplant at our center with adverse events possibly related to statins. Three cases of statin-induced rhabdomyolysis in patients with cirrhosis on ATV were identified. At baseline, all were Child-Pugh-Turcott (CPT) C.



Case 1 is a 62-year-old male with nonalcoholic steatohepatitis cirrhosis who presented after recent coronary stent placement and initiation of ATV 80mg with lower extremity discomfort, a CK 8,000 with rapid increase over 24 hours and severe acute kidney injury with hyperkalemia and arrhythmia requiring emergent hemodialysis and ultimately continuous renal replacement therapy. This resulted in cardiac arrest, and he was ultimately pronounced deceased.



Case 2 is a 76-year-old male with alcoholic cirrhosis on ATV 40 mg for hyperlipidemia (HLD). He presented with lower extremity weakness and rhabdomyolysis after starting ciprofloxacin for spontaneous bacterial peritonitis prophylaxis. Both medications were held and his symptoms improved.



Case 3 is a 51-year-old male with alcoholic cirrhosis undergoing liver transplant evaluation on ATV 40mg for HLD who was noted to have lower extremity myalgias, elevated AST, and a CK > 14,000. Imaging showed bilateral thigh myositis. He improved with discontinuation of ATV; his symptoms were attributed to statin-induced myotoxicity.



Discussion: Many statins are metabolized by Cytochrome P450 system, therefore susceptible to liver dysfunction however there is a higher incidence of statin-induced rhabdomyolysis specifically with those metabolized by CYP3A4 like ATV. The risk increases with dosages; ATV Cmax and AUC are approximately 16-fold and 11-fold increased, respectively, in patients with CPT B. Although statins improve disease progression and mortality in CLD, the benefits become less defined with advanced liver disease. Patients are often on statins due to coexisting CVD or after cardiac evaluation for liver transplant. It is important to be cognizant of this risk when initiating statins or other CYP3A4-regulated medications (e.g. Ciprofloxacin) while on statins, or opt for preferential treatment with agents like Rosuvastatin.



Disclosures:


Karine Moussa, MD¹, Ashwini Mulgaonkar, MD², Adam Deising, MD², Jennifer Au, MD², Julio Gutierrez, MD². P1113 - Risk of Atorvastatin Toxicity in Individuals With Hepatic Impairment, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.