The efficacy and safety of glecaprevir plus pibrentasvir in 141 patients with severe renal impairment: a prospective, multicenter study

Autor: Chikara Ogawa, Katsuhiko Iwakiri, Hiroshi Abe, Takashi Kumada, Haruki Uojima, Shinya Fukunishi, Naoki Hotta, Tadashi Ikegami, Akito Nozaki, Takuya Genda, Kunihiko Tsuji, Makoto Nakamuta, Chisa Kondo, Noritomo Shimada, Yasuhito Tanaka, Hidenori Toyoda, Takehiro Akahane, Koichi Takaguchi, Tsunamasa Watanabe, Masanori Atsukawa, Yoshio Aizawa, Yoshihiko Tachi, Kojiro Michitaka, Toshihide Shima, Akihito Tsubota
Rok vydání: 2019
Předmět:
Adult
Cyclopropanes
Male
Drug
medicine.medical_specialty
Aminoisobutyric Acids
Pyrrolidines
Proline
Sustained Virologic Response
Lactams
Macrocyclic
media_common.quotation_subject
Antiviral Agents
Severity of Illness Index
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Leucine
Renal Dialysis
Quinoxalines
Internal medicine
Humans
Medicine
Pharmacology (medical)
Prospective Studies
030212 general & internal medicine
Renal Insufficiency
Chronic
Stage (cooking)
Adverse effect
Aged
media_common
Aged
80 and over
Sulfonamides
Hepatology
business.industry
Incidence (epidemiology)
Gastroenterology
Glecaprevir
Hepatitis C
Chronic
Middle Aged
medicine.disease
Pibrentasvir
Benzimidazoles
Drug Therapy
Combination
Female
030211 gastroenterology & hepatology
business
Kidney disease
Zdroj: Alimentary Pharmacology & Therapeutics. 49:1230-1241
ISSN: 0269-2813
DOI: 10.1111/apt.15218
Popis: BACKGROUND Patients with chronic hepatitis C are often complicated by chronic kidney disease (CKD). AIM To evaluate the efficacy, safety and pharmacokinetics of glecaprevir/pibrentasvir in patients with severe renal impairment. METHODS In a prospective, multicentre study involving 35 medical institutions, 832 genotype 1-3 patients were treated with glecaprevir/pibrentasvir. The efficacy and safety of glecaprevir/pibrentasvir were analysed for patients with CKD stage 4 or 5. Multivariate analysis was performed to identify the factors associated with the most frequently observed adverse event. In patients undergoing haemodialysis, a pharmacokinetic study was conducted to investigate the dialysability of the drugs: plasma samples were obtained from the arterial and venous sides of a dialyser to serially measure drug concentrations. RESULTS The subjects comprised 141 patients (32 with CKD stage 4 and 109 with CKD stage 5), of whom 100 were undergoing haemodialysis. All but one stage 5 CKD patients undergoing haemodialysis achieved sustained virologic response (99.3%). Adverse events were observed in 39.7% of subjects: pruritus was the most frequent (30.5%), and was significantly associated with haemodialysis. In the pharmacokinetic study, no arterial-venous differences in the plasma concentrations of glecaprevir/pibrentasvir were detected during the haemodialysis sessions. CONCLUSIONS Glecaprevir/pibrentasvir was highly effective and safe in chronic hepatitis C patients with severe renal impairment. Haemodialysis was associated with increased incidence of pruritus, which was the most frequent adverse event, but had little or no influence on the drug concentrations, which indicated that their dialysability is very low and that no dose modification is required in patients undergoing haemodialysis. (UMIN registration no. 000032073).
Databáze: OpenAIRE
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