All drugs used in hepatitis C virus (HCV) treatment can be used in patient with compensated liver cirrhosis (Child-Pugh score A). |
All drugs used in HCV treatment can be used in patients with moderate renal insufficiency (glomerular filtration rate [GFR] ≥30 mL/min). |
In patients with GFR ≤29 mL/min or advanced liver disease, HCV drugs might be contraindicated or dosage adjustments may be necessary. |
1 Introduction
2 Methods
3 Pharmacokinetics
HCV drug
|
Normal hepatic function
|
Degree of dirrhosis
| ||
---|---|---|---|---|
Child-Pugh score A
|
Child-Pugh score B
|
Child-Pugh score C
| ||
Simeprevir | 150 mg od [11] | 150 mg od [11] | ||
Asunaprevir*
| ||||
Daclatasvir | 60 mg od [18] | 60 mg od [18] | 60 mg od [18] | 60 mg od [18] |
Sofosbuvir | 400 mg od [23] | 400 mg od [23] | 40 0mg od [23] | 400 mg od [23] |
Ledipasvir/sofosbuvir | 90 mg od/400 mg od [21] | 90 mg od/400 mg od [21] | 90 mg od/400 mg od [21] | 90 mg od/400 mg od [21] |
Velpatasvir/sofosbuvirb
| 100 mg od/ 400 mg od [37] | Unknown | ||
Grazoprevir/elbasvir | Contraindicated [50] | Contraindicated [50] | ||
Ombitasvir/paritaprevir/ritonavir | Contraindicated [51] | |||
Dasabuvir | Contraindicated [53] | |||
Ribavirin | <75kg = 500 mg bid≥75kg = 600 mg bid [56] | <75kg = 500 mg bid≥75kg = 600 mg bid [56] | <75kg = 500 mg bid≥75kg = 600 mg bid [56] | <75kg = 500 mg bid≥75kg = 600 mg bid [56] |
HCV drug
|
Normal renal function
|
Degree of renal impairment
|
Removed by dialysis?
| |||
---|---|---|---|---|---|---|
GFR >90 mL/min
|
Mild (GFR 50-89 mL/min))
|
Moderate (GFR 30-49 mL/min)
|
Severe (GFR 15-29 mL/min)
|
ESRD (GFR <15 mLl/min)
| ||
Simeprevir | 150 mg od [11] | 150 mg od [11] | 150 mg od[11] | 150 mg od[11]a
| 150 mg od[11]a
| No |
Asunaprevirb
| 100 mg bid [17] | 100 mg bid [17] | 100 mg bid [17] | 100 mg od [17] | Unknown | |
Daclatasvir | 60 mg od [18] | 60 mg od [18] | 60 mg od [18] | 60 mg od[18] | No | |
Sofosbuvir | 400 mg od [23] | 400 mg od [23] | 400 mg od [23] | Yes, administer after dialysis | ||
Velpatasvir/sofosbuvirb
| 100 mg od/400 mg od [37] | Unknown | Unknown | Unknown | Unknown | Unknown |
Sofosbuvir | 90 mg od/400 mg od [21] | 90 mg od/400 mg od [21] | 90 mg od/400 mg od [21] | Unknown | Unknown | Ledipasvir = no [21] GS-331007 = yes [23] |
Grazoprevir/elbasvir | 100 mg od/50 mg od [50] | 100 mg od/50 mg od [50] | 100 mg od/50 mg od [50] | 100 mg od/50 mg od [50] | 100 mg od/50 mg od [50] | Elbasvir = no |
Ombitasvir/paritaprevir/ritonavir | 25 mg od/150 mg od/100 mg od [51] | 25 mg od/150 mg od/100 mg od [51] | 25 mg od/150 mg od/100 mg od [51] | 25 mg od/150 mg od/100 mg od [51] | 25 mg od/150 mg od/100 mg od [80] | Unknown |
Dasabuvir | 250 mg bid [53] | 250 mg bid [53] | 250 mg bid [53] | 250 mg bid [53] | 250 mg bid [80] | Unknown |
Ribavirin | <75 kg = 500 mg bid≥75 kg = 600 mg bid [56] | <75 kg = 500 mg bid≥75 kg = 600 mg bid [56] | Loading dose: <75 kg = 50 0mg bid for 1 day ≥75kg = 600 mg bid for 1 day. Followed by alternating 200 and 400 mg od [95] TDM ribavirind
| Loading dose: <75kg = 500mg bid for 1 day ≥75kg = 600mg bid for 1 day. Followed by 200mg od [95] TDM ribavirind
| Loading dose: <75kg = 500 mg bid, for 1 day ≥75kg = 600 mg bid for 1 day. Followed by 200 mg od [95] TDM ribavirind
| No [56] |
3.1 Protease Inhibitors
3.1.1 Simeprevir
3.1.2 Asunaprevir
3.2 NS5A Inhibitors
3.2.1 Daclatasvir
3.3 NS5B Polymerase Inhibitors
3.3.1 Sofosbuvir
3.4 Fixed-Dose Regimens
3.4.1 Ledipasvir/Sofosbuvir
3.4.2 Velpatasvir/Sofosbuvir
3.4.3 Grazoprevir/Elbasvir
3.4.4 Paritaprevir/Ritonavir, Ombitasvir, and Dasabuvir
3.5 Other Antivirals
3.5.1 Ribavirin
4 Efficacy and Safety
Population and treatment (dose)
|
Study design
|
N
|
SVR rates (%)
|
Patients with SAEs (%)
|
Patients with AEs (%)
|
Patients who: discontinued (%) / discontinued due to (S)AEs (%)
|
(S)AEs reported with rates ≥10%
|
Reference
|
---|---|---|---|---|---|---|---|---|
CP-A/B, GT 1
Sofosbuvir 400 mg od, simeprevir 150 mg od± weight-based ribavirin | Retrospective | 119 | CP-A: 78 CP-B: 29 | 1 | 22 | NR / 3 | Anemia (72 % - ribavirin group) | [63] |
Cirrhosis, GT 1 and 4
Sofosbuvir 400 mg od, simeprevir 150 mg od± ribavirin | Prospective, open-label | 108 | 77 | NR | NR | NR / 0 | Fatigue (40 %) Nausea (10 %) Headache (10 %) | [74] |
CP-A, GT 1
CP-B/C, GT 1
Sofosbuvir 400 mg od, simeprevir 150 mg od± ribavirin | Retrospective | 101 55 | 91 73 | NR NR | NR NR | 1 / 111 / 9 | NR NR | [64] |
Cirrhosis, GT 2
Sofosbuvir 400 mg od ± weight-based ribavirina
| Phase IV, open-label | 66 | 79 | 12 | 88 | 10 / 5 | Fatigue (33 %) Anemia (24 %) Nausea (18 %) Headache (17 %) Hemoglobin < 10 g/dL (12 %) | [73] |
CP-A/B/C, GT 1-6
Daclatasvir 60 mg od, sofosbuvir400 mg od + 600mg ribavirin potential adjustments up to 1000 mg | Phase II, prospective, open-label | 60 | 83 | 17 | 18 (grade 3/4) | NR / 2 | Anemia (20 %) Fatigue (18 %) Nausea (17 %) Total bilirubin > 2.5 X ULN (15 %) Headache (15 %) Lymphocytes <0.5 x 109/l (10 %) | [71] |
Cirrhosis, advanced fibrosis, GT 3
Daclatasvir 60 mg od, sofosbuvir 400mg od + weight-based ribavirin | Phase III open-label, randomized | 50 | SVR4 ≥88 | NR | NR | NR / 0 | Insomnia (30 %) Fatigue (26 %) Headache (24 %) | [72] |
Cirrhosis-fibroscan ≥ 14.6 kPa. GT 1b
Daclatasvir 60 mg od, asunaprevir 100mg bid | Phase III | 223 | 84 | 6 | NR | NR / 1 | Headache (25 %) Fatigue (20 %) Diarrhea (16 %) Nausea (11 %) | [69] |
Compensated cirrhosis (F4), GT 1
Daclatasvir 30 mg bid, asunaprevir 200 mg bid, beclabuvir 75 mg bid ± weight-based ribavirina
| Phase-3, open-label, randomized, uncontrolled | 202 | ≥87% | 5% | NR | NR / 4% | Headache (20 %) Fatigue (12 %) Nausea (15 %) Diarrhea (11 %) Insomnia (10 %) Pruritus (10 %) | [68] |
CP-B, GT 1, 3
CP-C, GT 1, 3
Ledipasvir 90 mg od, sofosbuvir 400 mg od± weight-based ribavirina
| Phase II, open-label, randomized | 59 49b
| ≥82 ≥91 | 22 35 | 98 100 | NR / 5 NR / 10 | NR NR | [75] |
CP 5-7, GT 1 and 4
Ledipasvir
90 mg od, sofosbuvir 400 mg od, ± weight-based ribavirina
| Randomized, double-blind, placebo-controlled | 155 | ≥96 | NR | 91 | NR / 1 | Asthenia (52 %) Headache (34 %) Pruritus (19 %) Insomnia (19 %) Nausea (14 %) Fatigue (14 %) Cough (14 %) Diarrhea (12 %) Myalgia (11 %) Arthralgia (11 %) Bronchitis (11 %) Back pain (10 %) Dry skin (10 %) Irritability (10 %) | [76] |
CP-B, GT 1-4, and 6
Velpatasvir 100 mg od, sofosbuvir 400 mg od (12 weeks) Velpatasvir 100 mg od, sofosbuvir 400 mg od ± weight-based ribavirina
Velpatasvir 100 mg od, sofosbuvir 400 mg od (24 weeks) | Phase III, open-label, randomized. | 90 87 90 | 83 94 86 | 19 16 18 | 81 91 81 | NR / 1 NR / 5 NR / 4 | Fatigue (26 %) Nausea (24 %) Headache (26 %) Platelets 25,000 to <50,000 per mm3 (17 %) Lymphocytes 350 to <500 per mm3 (11 %) Pruritus (11 %) Insomnia (10 %) Fatigue (39 %) Nausea (25 %) Anemia (31 %) Lymphocytes <500 per mm3 (28 %) Hemoglobin <10g/dl (23 %) Headache (21 %) Diarrhea (21 %) Insomnia (14 %) Muscle spasm (11 %) Platelets 25,000 to <50,000 per mm3 (11 %) Fatigue (23 %) Nausea (20 %) Platelets 25,000 to <50,000 per mm3 (20 %) Headache (19 %) Insomnia (10 %) | [77] |
CP-A, GT 1
c
Grazoprevir 100mg od, elbasvir 50 mg od ± 51-65 kg 800 mg, 66-80 kg 1000 mg 81–105 kg 1200 mg, 106–125 kg 1400 mg | Phase II, parallel group, open-label, randomized | 253 | ≥90 | 3 | 79 | NR / 1 | Fatigue (26 %) Headache (23 %) Asthenia (14 %) | [78] |
CP-A, GT 1
Grazoprevir 100 mg od, elbasvir 50 mg od, sofosbuvir 400 mg od | Phase II, open-label, interim analysis | 41 | SVR8 = 95% (n = 19) | 5 | NR | NR / 3 | NR | [94] |
CP-B, GT 1
Grazoprevir 50 mg od, elbasvir 50 mg od | Phase II, interim analysis | 30 | EOT = 100%(n = 25) | 13 | 87 | NR / 0 | Fatigue (30 %) Arthralgia (17 %) Hyperbilirubinemia grade 3/4 (13 %) Nausea (10 %) Pyrexia (10 %) Headache (10 %) | [49] |
CP-A, GT 1
Paritaprevir 150 mg od, ritonavir 100 mg od, ombitasvir 25 mg od, dasabuvir 250 mg bid ± weight-based ribavirinb
| Phase-3, randomized | 380 | ~94% | 6 | 91 | NR / 2 | Fatigue (39%) Headache (29%) Nausea (19%) Pruritus (19%) Insomnia (17%) Diarrhea (16%) Asthenia (13%) Rash (13%) Irritability (10 %) | [79] |
CP ≥5 and ≤7, GT 4
Paritaprevir 150 mg od, ritonavir 100 mg od, ombitasvir 25 mg od ± weight-based ribavirin | Phase II, randomized, open-label. Ongoing study | 111 | SVR not reported in abstract | 4 | NR | 2 / 0 | Fatigue (~15 %) Headache (~15 %) | [96] |
Population and treatment (dose)
|
Study design
|
N
|
SVR rates (%)
|
Patients with SAEs (%)
|
Patients with AEs (%)
|
Patients who: discontinued (%) / discontinued due to (S)AE s (%)
|
(S)AEs reported with rates ≥10 %
|
Reference
|
---|---|---|---|---|---|---|---|---|
GFR ≤15 mL/min or dialysis, GT 1
Sofosbuvir 400 mg every other day OR Sofosbuvir 200 mg od + simeprevir 150 mg od | Open-label, real life experience | 4 11 | 91 75 | 0 | 0 | NR / 0 | Fatigue (20 %) Anemia (13 %) Rash/itching (13 %) | [66] |
GFR <30 mL/min or ESRD, GT 1-3
Sofosbuvir 200 mg odOR Sofosbuvir 400 mg every other +simeprevir 150 mg od | Observational, interim-analysis | 28 | 90 (n = 21/23) | 10 | NR | NR / NR | Fatigue (20 %) Anemia (15 %) Rash/itching (10 %) | [67] |
GFR <15 mL/min or ESRD, GT 1a
Sofosbuvir 400 mg od, simeprevir 150 mg od | Observational cohort | 17 | 94 | NR | 23 | 0 / 0 | Insomnia (12 %) | [33] |
GFR <30 mL/min, GT 1, 3
Sofosbuvir 200 mg od, ribavirin 200 mg od | Open-label | 10 | 40 | 20 | 100 | NR / 10 | Anemia (50 %) Headache (40 %) Pruritus (30 %) Rash (30 %) Muscle spasms (20 %) Hypoesthesia (20 %) Insomnia (20 %) Irritability (20 %) | [27] |
GFR <30 mL/min, GT 1 and 3
Sofosbuvir 400 mg od, ribavirin 200 mg od | Open-label | 10 | SVR not reported in abstract | 20 | NR | 20 / 20 | Anemia (40 %) Dizziness (20 %) Grade 3 laboratory AE (60%) Grade 4 laboratory AE (10 %) | [28] |
GFR ≤ 30 mL/min
GFR 31-45 mL/min
GFR 46-60 mL/min
Sofosbuvir-containing regime for GT 1-6 + ribavirin | Longitudinal, observational cohort | 18 63 168 | 85 (n = 11/13) 81 (n = 30/37) 88 (n = 108/123) | 19 24 5 | NR NR NR | 9 / 6 8 / 5 4 / 2 | Anemia (31 %) Fatigue (19 %) Nausea (19 %) Fatigue (37 %) Anemia (28 %) Headache (16 %) Nausea (15 %) Fatigue (33 %) Anemia (23 %) Nausea (19 %) Headache (12 %) | [31] |
Dialysis, GT 1
Daclatasvir 60 mg od, asunaprevir 100 mg bid | Prospective, observational | 21 | 96 | 5 | 67 | NR / 5 | Nasopharyngitis (29 %) Anemia (29 %) Increased ALT (14 %) Pyrexia (10 %) | [70] |
GFR <29 mL/min, GT 1
a
Grazoprevir 100 mg od, elbasvir 50 mg od | Phase III, randomized, placebo-controlled | 111 | ~95 | 15 | 76 | NR / 0 | Headache (17 %) Nausea (15 %) Fatigue (10 %) | [48] |
GFR < 30mL/min, GT 1
Paritaprevir 150 mg od, ritonavir 100 mg od, ombitasvir 25 mg od, dasabuvir 250 mg bid ± ribavirin 200 mg od | Phase I, open-label, interim analysis | 20 | EOT = 100 (n = 14) SVR4 = 100 (n = 10) | 10 | NR | 0 / 0 | Anemia (40 %) Fatigue (30 %) Nausea (25 %) Diarrhea (25 %) Dizziness (15 %) Headache (15 %) Decreased appetite (1 0%) Irritability (10 %) Edema peripheral (10 %) Weight decrease (10 %) | [80] |