Effect of Hemodialysis on Efficacy and Pharmacokinetics of Sofosbuvir Coformulated with Either Daclatasvir or Ledipasvir in Patients with End-Stage Renal Disease

Abstract

Background/Aims: Direct-acting antivirals (DAAs) play a key role in the eradication of hepatitis C virus (HCV) infection. However, limited data are available on DAA for treating HCV infection in hemodialysis (HD) patients. This study was to evaluate the pharmacokinetic characteristics and effectiveness of daclatasvir/sofosbuvir (DAC/SOF) and ledipasvir/SOF (LDV/SOF) in HD patients. Methods: Seven patients were given SOF coadministered with DAC or LDV once daily for 12 weeks. The plasma concentrations of SOF007, DAC, and LDV were determined by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. Results: A sustained virologic response in week 12 (SVR12) was achieved in 6 (100%) patients, except for 1 patient dying due to severe cerebral hemorrhage not related to antiviral therapy. The extraction ratio of SOF007 was 66.67%, and the estimated HD clearance of SOF007 was 5.65 L/h. Conclusion: The combination of SOF with either DAC or LDV is well tolerated and offers high SVR12 in HD patients.

Efficacy and safety of sofosbuvir in the treatment of hep C among patients on hemodialysis: a systematic review and meta-analysis

“…The included studies were published from 2015 to 2020 and contained extractable data on 514 patients enrolled from 2014 to 2016. Four studies were retrospective [10][11][12][13] and 16 were prospective [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] . Nine of the studies were conducted in India 10,12,14,16,18,20,22,25,29 , 2 in the USA 15,21 , 2 in Pakistan 24,28 , 2 in China 19,27 , 1 in France 17 , the Czech Republic 11 , Korea 13 , Iraq 26 , and 1 enrolled patients from multiple countries 23 .…”

“…A total of 19 studies reported extractable data on the SOF dose [10][11][12][13][14][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and the other DAA included in the treatment regimen. In nine studies [10][11][12][13]16,19,[21][22][23] , the same treatment regimen was used for all study participants.…”

“…A sub-group analysis was not performed for the various other DAA used in the treatment regimens, due to the large variability of DAA used. Ribavirin was used in 6 studies 10,13,14,16,18,28 , simeprevir in 3 15,17,21 , ledipasvir in 8 17,[20][21][22][25][26][27]29 , daclatasvir in 9 10,11,14,[16][17][18][19][20][24][25][26][27][28][29] and velpatasvir in 2 studies 12,23 (Table 1).…”

“…A total of 16 studies reported extractable data on adverse events [10][11][12][13][14][16][17][18][19][21][22][23]25,[27][28][29] ( Table 2). The most commonly reported adverse events were anemia (10 studies) 10,[12][13][14][16][17][18]21,23,28 , headache (8 studies) 12,17,[21][22][23]25,27,29 , fatigue (6 studies) 13,16,17,19,23,25 , nausea or vomiting (5 studies) 19,21,23,25,29 , insomnia (5 studies) 13,19,21,23,29…”

“… 13 2017–2018 Retrospective Korea 9 59.9 66.7 GT-2:100 RBV 400 mg daily 9 (100%) Lin et al . 27 2017 Prospective China 7 53 71.4 GT-1b: 57, GT-2a: 29, GT-6: 14 DCV, LDV 400 mg daily 6 (86%) Debnath et al . 25 2017–2018 Prospective India 18 39.4 77.8% GT-1: 66.7, GT-2: 5.5, GT-3: 22.3, GT-5: 5.5 DCV, LDV 400 mg daily 18 (100%) Singh et al .…”