An Unexpected Interaction between Sofosbuvir/Ledipasvir and Atorvastatin and Colchicine Causing Rhabdomyolysis in a Patient with Impaired Renal Function

Abstract

Hepatitis C virus (HCV) infection affects roughly 170 million people worldwide. Sofosbuvir/Ledipasvir (Sof/Led) is a new once daily direct acting antiviral combination pill that was approved in October 2014 for use in patients with HCV genotype 1 infection. Coadministration of Sof/Led is studied only with rosuvastatin which shows significantly increased level of drug and is associated with increased risk of myopathy, including rhabdomyolysis. There is no mention of such HMG-CoA reductase inhibitor interaction as a class, as pravastatin did not have any clinically significant interaction with Sof/Led. Other myotoxic drugs, including colchicine are not studied. We present a case of a serious drug interaction between Sof/Led and atorvastatin, in the background of CKD and colchicine use.

Efficacy and safety of gout flare prophylaxis and therapy use in people with chronic kidney disease: a Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN)-initiated literature review

“… NEUSS 1986 [ 44 ] Case report eGFR of 23 (serum creatinine of 2.3 mg/dL) Gout flare prophylaxis 0.6 mg PO twice daily (long term) 1 1 No gout flare during therapy, but with multi-organ failure, including AKI (serum creatinine peaked at 3 mg/dL). PATEL 2016 [ 46 ] Case report eGFR of 32 (serum creatinine of 1.87 mg/dL) Gout flare prophylaxis 0.6 mg PO once daily (for > 5 years) 1 1 Efficacy data not available. Renal function deteriorated (serum creatinine peaked at 2.5 mg/dL) but returned to baseline upon colchicine cessation.…”

“…A total of 2325 studies of colchicine use were identified, as summarised in a PRISMA flowchart of the literature search (Supplementary Figure 1 ), and a final total of 49 studies were eligible for data extraction [ 9 – 57 ]. Twenty of these 49 studies, which were mostly case series or case reports, described the efficacy and/or safety outcomes of colchicine use stratified by renal function, as summarised in Tables 2 and 3 , respectively [ 17 , 18 , 20 , 22 , 24 , 28 , 29 , 31 – 33 , 35 – 37 , 39 , 44 , 46 , 49 , 53 , 55 , 57 ]. The remaining 29 studies reported efficacy and/or safety outcomes of colchicine use without renal function stratification, as summarised in Supplementary Table 2 and Supplementary Table 3 , respectively [ 9 – 16 , 19 , 21 , 23 , 25 – 27 , 30 , 34 , 38 , 40 – 43 , 45 , 47 , 48 , 50 – 52 , 54 , 56 ].…”

“… NEUSS 1986 [ 44 ] Yes Fatal colchicine toxicity with myopathy, multi-organ failure, severe neutropaenia with associated disseminated candidiasis and death. PATEL 2016 [ 46 ] Yes Colchicine-induced rhabdomyolysis in the context of statin use and initiation of sofosbuvir/ledipasvir therapy for Hepatitis C. RIEGER 1990 [ 49 ] Yes Colchicine neuromyopathy in the context of acute stage of post-renal transplant and cyclosporin use. WILBUR 2004 [ 53 ] Yes Colchicine neuromyopathy.…”

An Interaction Between Glecaprevir, Pibrentasvir, and Colchicine Causing Rhabdomyolysis in a Patient With Chronic Renal Disease

“…This is the first reported case of likely colchicine‐induced rhabdomyolysis due to interaction with G/P. An additional case of rhabdomyolysis has been reported in a patient with renal dysfunction being treated with the NS5A inhibitor ledipasvir and NS5B polymerase inhibitor sofosbuvir while continuing colchicine and atorvastatin . Unlike the prior case, our patient had a dose reduction of colchicine before initiation of HCV therapy and was not taking a statin that may have increased the muscle toxicity.…”

“…An additional case of rhabdomyolysis has been reported in a patient with renal dysfunction being treated with the NS5A inhibitor ledipasvir and NS5B polymerase inhibitor sofosbuvir while continuing colchicine and atorvastatin. 13 Unlike the prior case, our patient had a dose reduction of colchicine before initiation of HCV therapy and was not taking a statin that may have increased the muscle toxicity. Coadministration of colchicine and G/P is not prohibited, but this combination has not been studied.…”