bms-790052 and Anemia

Direct-acting antiviral agents (DAAs) have revolutionized treatment of chronic hepatitis C in patients with normal glomerular filtration rate (GFR). However, patients with impaired kidney function have been excluded from several clinical trials. We, therefore, investigated the use, effectiveness, and tolerability of DAAs in patients with GFR less than 30 ml/min in the real-world setting.. An analysis was done within the German Hepatitis C-Registry on 5733 patients including 46 individuals with a baseline GFR less than 30 ml/min treated with sofosbuvir-based (61%) or paritaprevir/ritonavir-based (39%) regimens.. Sustained virological response 12 rates did not differ significantly between patients with baseline GFR less than 30 versus more than 30 ml/min (91 vs. 96%). Nine individuals with a baseline GFR more than 30 ml/min presented with a GFR less than 30 ml/min at the end of treatment. GFR improvement from less than 30 ml/min to more than 30 ml/min was observed in 9/46 cases. Adverse events did not differ in patients with GFR less than 30 versus more than 30 ml/min. However, serious adverse events were significantly more frequent in individuals with GFR less than 30 ml/min and associated with ribavirin.. Different DAA therapies can be safely used with high sustained virological response rates in patients with GFR less than 30 ml/min. Ribavirin has to be avoided because of poor tolerability.

Topics: 2-Naphthylamine; Acute Disease; Adult; Aged; Anemia; Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Cyclopropanes; Disease Progression; Drug Therapy, Combination; Female; Fluorenes; Germany; Glomerular Filtration Rate; Hepatitis C, Chronic; Humans; Hypertension; Imidazoles; Lactams, Macrocyclic; Liver Cirrhosis; Macrocyclic Compounds; Male; Middle Aged; Pleural Effusion; Proline; Pyrrolidines; Registries; Renal Insufficiency, Chronic; Ribavirin; Ritonavir; RNA, Viral; Severity of Illness Index; Simeprevir; Sofosbuvir; Sulfonamides; Sustained Virologic Response; Treatment Outcome; Uracil; Uridine Monophosphate; Valine

To identify factors associated with the development of adverse drug reactions (ADR) in ribavirin therapeutic regimens.. A multicenter, prospective study was conducted in three public health hospitals in Rio de Janeiro between November 2015 and March 2018. Inclusion criteria were defined by patient follow-up at pharmaceutical consultation at the time of drug dispensing as those who used sofosbuvir in combination with simeprevir, daclatasvir, and/or ribavirin. All patients were invited to participate in the study during the first interview. Adverse drug reactions were reported according to the treatment regimen and frequency of occurrence. Statistical analysis was used to compare adverse reactions between treatments and their associated factors.. A total of 405 patients were included in the study (mean age 59.6 ± 9.6 years); 61.0% were female, 88.1% were infected with genotype 1, and 65.4% were cirrhotic. The most prescribed treatment was the combination of sofosbuvir, daclatasvir, and ribavirin (55.3%). The majority of patients reported at least one ADR during treatment (83.2%), of which fatigue, anemia, and headache were the most common. Being female (OR = 1.86, [1.08-3.20]) and use of ribavirin (OR: 2.39; 95% CI [1.38-4.13]) were predictors for the development of ADR, which was also associated with development of anemia (OR: 10.28; 95% CI: [5.78-18.30]). Treatment efficacy was 98.1%.. Direct-acting antiviral has been shown to be safe and effective. Therefore, use of ribavirin is questionable due to associated adverse reactions and similar efficacy to other treatments.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antiviral Agents; Brazil; Carbamates; Drug Therapy, Combination; Fatigue; Female; Headache; Hepatitis C, Chronic; Humans; Imidazoles; Longitudinal Studies; Male; Middle Aged; Product Surveillance, Postmarketing; Prospective Studies; Pyrrolidines; Ribavirin; Risk Factors; Sofosbuvir; Valine

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.

Topics: Aged; Anemia; Antiviral Agents; Carbamates; Cyclosporine; Drug Interactions; Drug Therapy, Combination; Female; Hepatitis C; HIV Infections; Humans; Imidazoles; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Pyrrolidines; Ribavirin; Sofosbuvir; Tacrolimus; Valine