Severe Myositis With the Use of Sofosbuvir/Ledipasvir for Hepatitis C Infection: A Case of Unexpected Interactions

Abstract

Case Report: This 66-year-old female presented to emergency room with one week of nausea, nonbloody vomiting, weakness and diarrhea. Her medical history was significant for compensated Hepatitis C (HCV) associated liver cirrhosis, prior treatment failure chronic HCV infection, stage III chronic kidney disease, coronary artery disease, and gout. She had started Ledipasvir/Sofosbuvir combination drug along with renally dosed Ribavirin a month prior to this admission. In addition she was on Atorvastatin and Colchicine for prior several months without any side effects. On admission, her HCV RNA was undetectable, creatine kinase (CK) was of 9055 U/L, ALT 166 U/L, AST 362 U/L, GFR 30 mL/min/1.73 m2, and a urinalysis was notable for large amount of blood but no RBCs, suggesting rhabdomyolysis. Atorvastatin was stopped on the day of admission and she was aggressively fluid resuscitated. Patient complained of profound weakness and myalgia. Initial workup was unremarkable, with normal aldolase, C3 and C4 complement, TSH, and serum protein electrophoresis. EMG showed diffuse muscle irritability suggesting inflammatory myopathy. The conclusion reached was that this patient's myositis was drug induced, possibly from interaction between Ledipasvir/Sofosbuvir, Atorvastatin and Colchicine. Colchicine was subsequently stopped. The rhabdomyolysis resolved and she had normal CK levels and although her myalgias improved, she was discharged home with persistent muscle weakness which subsequently improved over next 4 weeks as she continued her HCV treatment. Discussion: Ledipasvir/Sofosbuvir is a new Direct Acting Antiviral combination that was introduced in 2014 to treat chronic HCV genotype 1 infection in adults. Sofosbuvir's metabolite is renally excreted and patient's stage III CKD could have played a critical role in increasing the chance of unanticipated toxicity. Ledipasvir/Sofosbuvir is known to increase the blood concentration of Rosuvastatin, but Atorvastatin interaction has not been specifically studied, indicating that Ledipasvir/Sofosbuvir could interact with statins as a class. Based on the Naranjo probability scale (score of 6) this patient's adverse event correlates to an adverse drug reaction caused by interaction between Ledipasvir/Sofosbuvir, Atorvastatin, and Colchicine. Conclusion: It is important for physicians' prescribing Ledipasvir/Sofosbuvir to be aware of the potential drug interaction with all statins as a class and with Colchicine, in the setting of CKD so that appropriate medication changes can be made to avoid myositis and rhabdomyolysis.