Safety analysis of sofosbuvir and ledipasvir for treating hepatitis C

Abstract

In trials enrolling more than 3000 patients, LDV/SOF is well tolerated with a good safety and side-effect profile in diverse cohorts, including previous direct-acting antiviral (DAA) treatment failures, liver transplant recipients, decompensated cirrhosis and HIV/HCV co-infection. As with all DAAs, the potential for drug-drug interactions must be carefully evaluated, as demonstrated by recent post-marketing reports of symptomatic bradycardia when LDV/SOF is co-administered with amiodarone. Currently, dose recommendations cannot be given for patients with advanced renal disease. Trials in this population are ongoing, more study is warranted. When surveying the DAA regimens available, efficacy, safety and tolerability of LDV/SOF is comparable or better, and LDV/SOF provides an option with convenient single-tablet, once daily, ribavirin-free dosing with relatively few significant drug-drug interactions.

Dual antiviral therapy for HIV and hepatitis C – drug interactions and side effects

“…The safety of LDV has been confirmed in several trials that have enrolled > 3000 patients [40], LDV/SOF is well tolerated with a good side effect profile in diverse patient populations, including liver transplant recipients, decompensated cirrhosis and HIV-coinfected patients. The drug is minimally metabolized with > 98% of the dose primarily eliminated in the feces, with little role of renal excretion.…”

“…Similar results on HCV genotype 1 patients are obtained using the so-called 3D regimen that combines paritaprevir/RTV/ombitasvir/ dasabuvir with or without RBV ( Table 2). In the real world, combinations based on SOF are currently the most frequently prescribed, given its convenience (few pills once a day), safety profile and low potential for drug interactions [38][39][40]. In most places, the single tablet co-formulation of SOF and LDV has overtaken all other treatment options [41].…”

“…The fixed dose coformulation of SOF and LDV depicts low risk for clinically significant drug interactions, as LDV, such as SOF, is not metabolized by the CYP450 system and is a substrate for P-gp. However, the co-administration of SOF/LDV and ARV regimens containing TDF plus boosted PI with either RTV or cobicistat should be used cautiously, given the increased TDF exposure [40,78].…”

The levels of monoamine neurotransmitters and measures of mental and emotional health in HCV patients treated with ledipasvir (LDV) and sofosbuvir (SOF) with or without ribavirin (RBV)

“…[1] More than 4 million people in the United States and nearly 185 million patients globally are infected with HCV. [2,3] HCV causes a systemic infection with both hepatic manifestations (eg, cirrhosis and hepatocellular carcinoma) and extrahepatic manifestations involving multiple other organ systems (eg, integumentary, ocular, muscular, skeletal, nervous, endocrine, cardiovascular, respiratory, and urinary systems). [4–6] Chronic HCV infection has been shown to impair patient-reported outcomes (PROs), such as health-related quality of life (HRQOL) and work productivity, and also deficits in attention, concentration, memory, mood, and information processing speed, collectively referred as “brain fog.” [7–10] …”

Acute Myeloid Leukemia, E-coli bacteremia, Salmonella urinary tract infection, Clostridium Difficile colitis, Subarachnoid hemorrhage and Gastrointestinal bleeding in an HCV Cirrhotic Patienton newly approved Anti-HCV Medications

“…The most common reported adverse events were fatigue, headache, insomnia, and nausea [8]. Documented life threatening complications of the combination medicine includes symptomatic bradycardia especially with concurrent use of amiodarone [9] …”