Comparison of the effect of direct-acting antiviral with and without ribavirin on cyclosporine and tacrolimus clearance values: results from the ANRS CO23 CUPILT cohort.
Aged
Anemia
/ chemically induced
Antiviral Agents
/ administration & dosage
Carbamates
Cyclosporine
/ administration & dosage
Drug Interactions
Drug Therapy, Combination
Female
HIV Infections
/ drug therapy
Hepatitis C
/ drug therapy
Humans
Imidazoles
/ administration & dosage
Immunosuppressive Agents
/ administration & dosage
Liver Transplantation
Male
Middle Aged
Pyrrolidines
Ribavirin
/ administration & dosage
Sofosbuvir
/ administration & dosage
Tacrolimus
/ administration & dosage
Valine
/ analogs & derivatives
Anaemia
Liver fibrosis
Ribavirin
Tacrolimus
Journal
European journal of clinical pharmacology
ISSN: 1432-1041
Titre abrégé: Eur J Clin Pharmacol
Pays: Germany
ID NLM: 1256165
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
26
03
2019
accepted:
17
07
2019
pubmed:
7
8
2019
medline:
10
3
2020
entrez:
7
8
2019
Statut:
ppublish
Résumé
Direct-acting antiviral agents have demonstrated their efficacy in treating HCV recurrence after liver transplantation and particularly the sofosbuvir/daclatasvir combination. Pharmacokinetic data on both calcineurin inhibitors and direct-acting antiviral exposure in liver transplant recipients remain sparse. Patients were enrolled from the ANRS CO23 CUPILT cohort. All patients treated with sofosbuvir/daclatasvir with or without ribavirin were included in this study when blood samples were available to estimate the clearance of immunosuppressive therapy before direct-acting antiviral initiation and during follow-up. Apparent tacrolimus and cyclosporine clearances were estimated from trough concentrations measured using validated quality control assays. Sixty-seven mainly male patients (79%) were included, with a mean age of 57 years and mean MELD score of 8.2; 50 were on tacrolimus, 17 on cyclosporine. Ribavirin was combined with sofosbuvir/daclatasvir in 52% of patients. Cyclosporine clearance remained unchanged as well as tacrolimus clearance under the ribavirin-free regimen. Tacrolimus clearance increased 4 weeks after direct-acting antivirals and ribavirin initiation versus baseline (geometric mean ratio 1.81; 90% CI 1.30-2.52). Patients under ribavirin had a significantly higher fibrosis stage (> 2) (p = 0.02) and lower haemoglobin during direct-acting antiviral treatment (p = 0.02) which impacted tacrolimus measurements. Direct-acting antiviral exposure was within the expected range. Our study demonstrated that liver transplant patients with a recurrence of hepatitis C who are initiating ribavirin combined with a sofosbuvir-daclatasvir direct-acting antiviral regimen may be at risk of lower tacrolimus concentrations because of probable ribavirin-induced anaemia and higher fibrosis score, although there are no effects on cyclosporine levels. NCT01944527.
Identifiants
pubmed: 31384986
doi: 10.1007/s00228-019-02725-x
pii: 10.1007/s00228-019-02725-x
doi:
Substances chimiques
Antiviral Agents
0
Carbamates
0
Imidazoles
0
Immunosuppressive Agents
0
Pyrrolidines
0
Ribavirin
49717AWG6K
Cyclosporine
83HN0GTJ6D
Valine
HG18B9YRS7
daclatasvir
LI2427F9CI
Sofosbuvir
WJ6CA3ZU8B
Tacrolimus
WM0HAQ4WNM
Banques de données
ClinicalTrials.gov
['NCT01944527']
Types de publication
Journal Article
Multicenter Study
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1555-1563Références
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