Atorvastatin and almonertinib-induced myopathy in a polypharmacy context: a case report

Background: Statin-induced myopathy is a common adverse effect and the risk of myopathy is increased by interacting drugs, usually inhibitor of CYP3A4. Almonertinib is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and is a moderately sensitive substrate of CYP3A4. Here we report a case of myopathy probably caused by concomitant use of atorvastatin and almonertinib. Case summary: An 89-year-old male patient with coronary heart disease and lung cancer was admitted to the hospital due to worsened chest tightness and shortness of breath for one week. He had been taking almonertinib for 26 months, hybutimibe for 3 months and alirocumab for 1 month prior to admission. Atorvastatin was added because the patient failed to reach the target cholesterol concentration. He presented with myasthenia and markedly elevated his serum creatine kinase (CK) (2,103 U/L; normal range <164 U/L) 1 day later. Drug-induced myopathy was diagnosed with a probable drug-drug interaction between atorvastatin and almonertinib. After discontinuation of the two drugs, the patient's CK returned to normal. Conclusion: Almonertinib is a moderately sensitive substrate of CYP3A4, thereby may elevate statin concentration and increase the likelihood of developing myopathy. For patients who need to take almonertinib and cholesterol-lowering drugs simultaneously, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and cholesterol absorption inhibitors (such as ezetimibe and hybutimibe) can be considered instead of atorvastatin for the reduction of cardiovascular events.