BACKGROUND: Nucleoside analogues may induce mitochondrial toxicity, particularly didanosine. Ribavirin increases didanosine exposure, which might be clinically relevant when coadministered in HIV/HCV-coinfected patients. OBJECTIVE: To evaluate, among 89 patients receiving highly active antiretroviral therapy (HAART) and therapy for chronic hepatitis C, clinically relevant mitochondrial toxicity in those treated with concomitant ribavirin and didanosine (n=35, 39%). METHODS: From January 2000 to July 2002 longitudinal analysis of the incidence and clinical course of didanosine-related hyperamylasaemia, pancreatitis, hyperlactataemia/lactic acidosis or neuropathy. Risk factors were evaluated using univariate and multivariate Cox's proportional hazards model. RESULTS: Among 35 patients who received concomitant didanosine (400 mg/day in 86%) and ribavirin (> or = 10 mg/kg/day in 91%), 20 (57%) developed one or more adverse events after a mean of 87 days. Most frequent laboratory abnormalities were hyperamylasaemia (18 patients, 51%) and hyperlactataemia (eight patients, 23%). Acute pancreatitis and symptomatic hyperlactataemia developed in 10 (28%) and six (17%) patients, respectively. Two patients (6%) with pancreatitis and severe lactic acidosis died; the other patients recovered uneventfully despite continuation of anti-HCV therapy in 83% after didanosine withdrawal in 40%. In the Cox's model higher baseline amylase levels (HR: 1.04, 95% CI: 1.02-1.06, P=0.001) and three nucleoside reverse transcriptase inhibitor-based HAART (HR: 5.3, 95% CI: 1.73-16.24, P=0.003) were significantly associated to toxicity. CONCLUSIONS: The coadministration of didanosine and ribavirin should be avoided in HIV/HCV-coinfected patients, due to a high rate of clinically significant toxicity, particularly in triple nucleoside-based HAART. Amylase levels should be strictly monitored, especially if elevated at baseline.
BACKGROUND:Nucleoside analogues may induce mitochondrial toxicity, particularly didanosine. Ribavirin increases didanosine exposure, which might be clinically relevant when coadministered in HIV/HCV-coinfectedpatients. OBJECTIVE: To evaluate, among 89 patients receiving highly active antiretroviral therapy (HAART) and therapy for chronic hepatitis C, clinically relevant mitochondrial toxicity in those treated with concomitant ribavirin and didanosine (n=35, 39%). METHODS: From January 2000 to July 2002 longitudinal analysis of the incidence and clinical course of didanosine-related hyperamylasaemia, pancreatitis, hyperlactataemia/lactic acidosis or neuropathy. Risk factors were evaluated using univariate and multivariate Cox's proportional hazards model. RESULTS: Among 35 patients who received concomitant didanosine (400 mg/day in 86%) and ribavirin (> or = 10 mg/kg/day in 91%), 20 (57%) developed one or more adverse events after a mean of 87 days. Most frequent laboratory abnormalities were hyperamylasaemia (18 patients, 51%) and hyperlactataemia (eight patients, 23%). Acute pancreatitis and symptomatic hyperlactataemia developed in 10 (28%) and six (17%) patients, respectively. Two patients (6%) with pancreatitis and severe lactic acidosis died; the other patients recovered uneventfully despite continuation of anti-HCV therapy in 83% after didanosine withdrawal in 40%. In the Cox's model higher baseline amylase levels (HR: 1.04, 95% CI: 1.02-1.06, P=0.001) and three nucleoside reverse transcriptase inhibitor-based HAART (HR: 5.3, 95% CI: 1.73-16.24, P=0.003) were significantly associated to toxicity. CONCLUSIONS: The coadministration of didanosine and ribavirin should be avoided in HIV/HCV-coinfectedpatients, due to a high rate of clinically significant toxicity, particularly in triple nucleoside-based HAART. Amylase levels should be strictly monitored, especially if elevated at baseline.
Authors: M Rodriguez-Torres; F J Torriani; V Soriano; M J Borucki; E Lissen; M Sulkowski; D Dieterich; K Wang; J-M Gries; P G Hoggard; D Back Journal: Antimicrob Agents Chemother Date: 2005-10 Impact factor: 5.191
Authors: Pankaj Puri; Anil C Anand; Vivek A Saraswat; Subrat K Acharya; Shiv K Sarin; Radha K Dhiman; Rakesh Aggarwal; Shivaram P Singh; Deepak Amarapurkar; Anil Arora; Mohinish Chhabra; Kamal Chetri; Gourdas Choudhuri; Vinod K Dixit; Ajay Duseja; Ajay K Jain; Dharmesh Kapoor; Premashis Kar; Abraham Koshy; Ashish Kumar; Kaushal Madan; Sri P Misra; Mohan V G Prasad; Aabha Nagral; Amarendra S Puri; R Jeyamani; Sanjiv Saigal; Samir Shah; Praveen K Sharma; Ajit Sood; Sandeep Thareja; Manav Wadhawan Journal: J Clin Exp Hepatol Date: 2014-06-24