• Keywords
• ombitasvir, dasabuvir, paritaprevir,
• MeSH
• Anilides pharmacology   therapeutic use   MeSH
• Antiviral Agents * pharmacology   therapeutic use   MeSH
• Drug Combinations MeSH
• Hepatitis C * drug therapy   MeSH
• Drug Evaluation MeSH
• Carbamates pharmacology   therapeutic use   MeSH
• Clinical Studies as Topic MeSH
• Drug Therapy, Combination MeSH
• Humans MeSH
• Macrocyclic Compounds pharmacology   therapeutic use   MeSH
• Ritonavir pharmacology   therapeutic use   MeSH
• Sulfonamides pharmacology   therapeutic use   MeSH
• Uracil pharmacology   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH

Vector-borne flaviviruses (VBFs) affect human health worldwide, but no approved drugs are available specifically to treat VBF-associated infections. Here, we performed in silico screening of a library of U.S. Food and Drug Administration-approved antiviral drugs for their interaction with Zika virus proteins. Twelve hit drugs were identified by the docking experiments and tested in cell-based antiviral assay systems. Efavirenz, tipranavir, and dasabuvir at micromolar concentrations were identified to inhibit all VBFs tested; i.e., two representatives of mosquito-borne flaviviruses (Zika and West Nile viruses) and one representative of flaviviruses transmitted by ticks (tick-borne encephalitis virus). The results warrant further research into these drugs, either individually or in combination, as possible pan-flavivirus inhibitors.

• Publication type
• Journal Article MeSH

• Publication type
• Meeting Abstract MeSH

BACKGROUND/AIMS: Chronic hepatitis C (HCV) virus infection reactivates under immunosuppressive drugs and therefore has a negative impact on long-term survival of kidney transplant recipients. Treatment-induced clearance of hepatitis C virus (HCV) in kidney transplant candidates prevents virus reactivation after transplantation. Paritaprevir/Ritonavir/Ombitasvir with Dasabuvir (PrOD) represents a highly effective treatment regimen for HCV genotype 1 (GT1), also suitable for patients with end-stage renal disease (ESRD). Serious drug-drug interactions may represent a limiting factor of this regimen. The aim of this retrospective study was to evaluate safety, efficacy and drug-drug interactions management associated with PrOD treatment in the Czech real-world cohort. METHODS: Emphasizing concomitant medication adjustment, we described the treatment course with PrOD regimen in 23 patients (4 with CKD4 and 19 on maintenance haemodialysis) infected with HCV GT1 (21 GT1b, 2 GT1a), 18 males and 5 females with an average age of 53.7 years. Six patients had compensated liver cirrhosis and 3 of them were liver transplant recipients. RESULTS: All 23 patients completed the 12-week treatment and achieved sustained virological response 12 weeks after the treatment (SVR12 rate 100%). None of the patients presented with a significant decrease in haemoglobin level, white blood cell and platelet count during the treatment period. The most frequent adverse events were nausea, hypotension, diarrhoea, and hyperkalemia. Four patients presented with a serious adverse event unrelated to the antiviral drugs (salmonellosis, non-functional kidney graft rejection, early gastric cancer, renal cyst infection, initiation of haemodialysis). Concomitant medication had to be modified with the treatment initiation in 10 out of 23 (43.5%) patients (calcium channel blockers, ACE inhibitors, statins, diuretics, tacrolimus); four patients required further adjustment of antihypertensive drugs or tacrolimus dosage on-treatment. CONCLUSION: PrOD regimen demonstrated an excellent efficacy and good tolerability. Both prospective adjustment of concomitant medication and further on-treatment adjustment allowed for a safe treatment course.

• MeSH
• Anilides therapeutic use   MeSH
• Antihypertensive Agents therapeutic use   MeSH
• Antiviral Agents adverse effects   therapeutic use   MeSH
• Hepatitis C, Chronic complications   drug therapy   virology   MeSH
• Kidney Failure, Chronic therapy   virology   MeSH
• Genotype MeSH
• Hepacivirus drug effects   genetics   MeSH
• Carbamates therapeutic use   MeSH
• Drug Therapy, Combination MeSH
• Middle Aged MeSH
• Humans MeSH
• Macrocyclic Compounds therapeutic use   MeSH
• Renal Insufficiency therapy   virology   MeSH
• Ritonavir therapeutic use   MeSH
• Sulfonamides therapeutic use   MeSH
• Uracil analogs & derivatives   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Léčba chronické hepatitidy C kombinací přímo působících perorálních virostatik (Directly Acting Antivirals – DAA) má vysokou účinnost (až 100 %), minimum kontraindikací a mimořádně příznivý bezpečnostní profil. Pozornost je nutné věnovat především lékovým interakcím, které jsou však dobře zdokumentované a uspokojivě řešitelné i v běžné klinické praxi. Současné možnosti bezinterferonové léčby představují kombinace sofosbuviru s jinými DAA nebo s ribavirinem a kombinace paritapreviru potencovaného ritonavirem + ombitasvir ? dasabuvir ? ribavirin. Klíčová slova: chronická hepatitida C – paritaprevir – ombitasvir – dasabuvir – ribavirin

Chronic hepatitis C therapy using Directly Acting Antivirals (DAA) has high efficacy (till 100 %), minimum contra-indications and extraordinarily favorable safety profile. Primarily, it is necessary to pay attention to drug-drug interactions. However they are well documented and successfully resolvable already in general clinical practice. Current possibilities of interferon-free therapy represent combinations of sofosbuvir with other DAA or with ribavirin and combination of paritaprevir boosted by ritonavir + ombitasvir ? dasabuvir (3D combination). Key words: chronic hepatitis C – paritaprevir – ombitasvir – dasabuvir – ribavirin

• Keywords
• ombitasvir, dasabuvir, paritaprevil, Viekirax, Exviera, přímo působící virostatika (Directly Acting Antivirals – DAA),
• MeSH
• Anilides administration & dosage   adverse effects   therapeutic use   MeSH
• Antiviral Agents * administration & dosage   adverse effects   therapeutic use   MeSH
• Hepatitis C, Chronic * diagnosis   drug therapy   MeSH
• Drug Combinations MeSH
• Genotype MeSH
• Interferon-alpha contraindications   MeSH
• Liver Cirrhosis complications   MeSH
• Carbamates administration & dosage   adverse effects   therapeutic use   MeSH
• Drug Therapy, Combination * MeSH
• Drug Interactions MeSH
• Humans MeSH
• Macrocyclic Compounds administration & dosage   adverse effects   therapeutic use   MeSH
• Polyethylene Glycols contraindications   MeSH
• Recombinant Proteins contraindications   MeSH
• Ribavirin administration & dosage   adverse effects   therapeutic use   MeSH
• Practice Guidelines as Topic MeSH
• Sofosbuvir MeSH
• Sulfonamides administration & dosage   adverse effects   therapeutic use   MeSH
• Uracil analogs & derivatives   administration & dosage   adverse effects   therapeutic use   MeSH
• Uridine Monophosphate MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Práce prezentuje první reálná data o úspěšnosti bezinterferonové léčby chronické hepatitidy C v ČR. Pacienti byli léčeni kombinovanou terapií paritaprevir/ritonavir + ombitasvir + dasabuvir s ribavirinem nebo bez něj. Soubor tvořilo 109 pacientů, převážně mužů (62; 57 %). Převládajícím genotypem byl subtyp 1b (101 ze 109 pacientů; 93 %), infekce subtypem 1a byla přítomna u šesti (5 %) a genotypem 4 u dvou (2 %) nemocných. Byli léčeni jak pacienti dříve neléčení – naivní (43 ze 109; 39 %), tak již v minulosti neúspěšně léčení kombinací pegylovaného interferonu a ribavirinu (66 ze 109; 61 %). Setrvalé virologické odpovědi 12 týdnů po ukončení terapie (SVR12) bylo dosaženo u 107 pacientů (98,2 %). Pokud z analýzy vyloučíme dva pacienty, kteří nedosáhli SVR12 z jiného důvodu než virologického selhání léčby, byla úspěšnost léčby 100%.

The first real-life data regarding the efficacy of interferon-free therapy for chronic hepatitis C in the Czech Republic are presented. Patients were treated with the combined therapy of paritaprevir/ritonavir plus ombitasvir plus dasabuvir with or without ribavirin. There were 109 patients, who were predominantly men (62, 57%). Most patients were infected by subtype 1b (101, 93%); six patients (5%) had subtype 1a infections and two patients (2%) had genotype 4 infections. Both treatment-naive (43/109, 39%) and pegylated interferon- and ribavirin-experienced patients (66/109, 61%) were treated. A sustained virological response 12 weeks after therapy termination was achieved in 107 patients (98.2%). After excluding two patients from the analyses for reasons other than virological treatment failure, the treatment efficacy was 100%.

• Keywords
• ombitasvir, dasabuvir, paritaprevir, Viekirax, Exviera,
• MeSH
• Anilides pharmacology   therapeutic use   MeSH
• Antiviral Agents * pharmacology   therapeutic use   MeSH
• Adult MeSH
• Drug Combinations MeSH
• Hepatitis C * drug therapy   MeSH
• Drug Evaluation MeSH
• Carbamates pharmacology   therapeutic use   MeSH
• Clinical Studies as Topic MeSH
• Drug Therapy, Combination MeSH
• Middle Aged MeSH
• Humans MeSH
• Ribavirin pharmacology   therapeutic use   MeSH
• Ritonavir pharmacology   therapeutic use   MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH

• Keywords
• ombitasvir, paritaprevir, dasabuvir,
• MeSH
• Antiviral Agents therapeutic use   MeSH
• Hepatitis C, Chronic * drug therapy   complications   MeSH
• Liver Cirrhosis diagnosis   etiology   therapy   MeSH
• Clinical Studies as Topic MeSH
• Congresses as Topic MeSH
• Cryoglobulinemia MeSH
• Humans MeSH
• Glomerulonephritis, Membranous etiology   therapy   MeSH
• Renal Insufficiency etiology   drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• News MeSH

• Keywords
• dasabuvir, ombitasvir, paritaprevir,
• MeSH
• Anilides pharmacokinetics   pharmacology   adverse effects   therapeutic use   MeSH
• Antiviral Agents * pharmacokinetics   pharmacology   adverse effects   therapeutic use   MeSH
• Hepatitis C, Chronic * drug therapy   genetics   MeSH
• Drug Combinations MeSH
• Liver Cirrhosis etiology   drug therapy   MeSH
• Carbamates pharmacokinetics   pharmacology   adverse effects   therapeutic use   MeSH
• Drug Therapy, Combination MeSH
• Drug Interactions MeSH
• Humans MeSH
• Ritonavir adverse effects   therapeutic use   MeSH
• Sulfonamides pharmacokinetics   pharmacology   adverse effects   therapeutic use   MeSH
• Uracil analogs & derivatives   pharmacokinetics   pharmacology   adverse effects   therapeutic use   MeSH
• Drug Resistance, Viral MeSH
• Viral Load MeSH
• Check Tag
• Humans MeSH

Léčba chronické hepatitidy C kombinací přímo působících perorálních virostatik (Directly Acting Antivirals – DAA) má vysokou účinnost (až 100%), minimum kontraindikací a mimořádně příznivý bezpečnostní profil. Pozornost je nutné věnovat především lékovým interakcím, které jsou však dobře zdokumentované a uspokojivě řešitelné i v běžné klinické praxi. Současné možnosti bezinterferonové léčby představují kombinace sofosbuviru s jinými DAA nebo s ribavirinem a kombinace paritaprevir potencovaný ritonavirem + ombitasvir ± dasabuvir. V některých zemích světa je již dostupná i fixní kombinace elbasviru s grazoprevirem.

Chronic hepatitis C therapy using Directly Acting Antivirals (DAA) has high efficacy (till 100%), minimum contra-indications and extraordinarily favorable safety profile. Primarily, it is necessary to pay attention to drug-drug interactions. However they are well documented and successfully resolvable already in general clinical practice. Current possibilities of interferon-free therapy represent combinations of sofosbuvir with other DAA or with ribavirin and combination of paritaprevir boosted by ritonavir + ombitasvir ± dasabuvir. Fixed combinaton of elbasvir and grazoprevir is already available in some countries of the world.

• Keywords
• přímo působící antivirotika, Directly Acting Antivirals (DAA),
• MeSH
• Antiviral Agents * therapeutic use   MeSH
• Hepatitis C, Chronic * drug therapy   MeSH
• Drug Combinations * MeSH
• Liver Cirrhosis diagnosis   complications   MeSH
• Humans MeSH
• Sofosbuvir therapeutic use   MeSH
• Patient Selection MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Léčba chronické hepatitidy C kombinací přímo působících perorálních virostatik (Directly Acting Antivirals – DAA) má vysokou účinnost (až 100 %), minimum kontraindikací a mimořádně příznivý bezpečnostní profil. Pozornost je nutné věnovat především lékovým interakcím, které jsou však dobře zdokumentované a uspokojivě řešitelné i v běžné klinické praxi. Současné možnosti bezinterferonové léčby představují kombinace sofosbuviru s jinými DAA nebo s ribavirinem a kombinace paritaprevir potencovaný ritonavirem + ombitasvir ± dasabuvir. V některých zemích světa je již dostupná i fixní kombinace elbasviru s grazoprevirem.

Chronic hepatitis C therapy using Directly Acting Antivirals (DAA) has high efficacy (till 100 %), minimum contra-indications and extraordinarily favorable safety profile. Primarily, it is necessary to pay attention to drug-drug interactions. However they are well documented and successfully resolvable already in general clinical practice. Current possibilities of interferon-free therapy represent combinations of sofosbuvir with other DAA or with ribavirin and combination of paritaprevir boosted by ritonavir + ombitasvir ± dasabuvir. Fixed combinaton of elbasvir and grazoprevir is already available in some countries of the world.

• Keywords
• přímo působící antivirotika, Directly Acting Antivirals (DAA),
• MeSH
• Antiviral Agents * therapeutic use   MeSH
• Hepatitis C, Chronic * drug therapy   MeSH
• Drug Combinations * MeSH
• Liver Cirrhosis diagnosis   complications   MeSH
• Humans MeSH
• Sofosbuvir therapeutic use   MeSH
• Patient Selection MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH