PPIs may decrease the effectiveness of hepatitis C antivirals

Abstract

Sustained virologic responses (SVRs) were lower in patients with hepatitis C taking direct-acting antivirals with proton pump inhibitors (PPIs) compared with those not receiving PPIs, according to results of a comprehensive review published in the Journal of Clinical and Translational Hepatology. Acid-reducing medications have been shown to decrease the concentrations of select hepatitis C treatments such as ledipasvir/sofosbuvir (Harvoni—Gilead) and sofosbuvir/velpatasvir (Epclusa—Gilead). However, previous research about the effects of concurrent use of PPIs and direct-acting antivirals on SVRs in patients with hepatitis C has been inconsistent. A systematic review and meta-analysis were conducted to assess the effects of PPIs on SVRs in patients with hepatitis C receiving a variety of direct-acting antivirals. Nine cohort studies involving 32,684 patients were included in the analysis. Seven of these nine studies assessed the interaction between PPIs and ledipasvir/sofosbuvir. The analysis showed that there were lower odds of achieving an SVR in patients who were on concurrent PPIs compared with those not on PPI therapy. A similar trend was observed for achieving an SVR at 12 weeks. The results remained the same even after adjusting for select confounding factors. The authors of the current analysis concluded that the study “demonstrated a significantly increased risk of failure of achievement of SVR in [hepatitis C virus]–infected patients taking [direct-acting antivirals] with PPIs compared to non-PPI users. Providers should consider whether PPI therapy is indicated for these patients and withdraw PPI therapy in the absence of indications.” An assessment of the labels for various direct-acting antivirals showed that they include cautions on potential drug interactions with PPIs. For example, the prescribing information for ledipasvir/sofosbuvir noted that the solubility of ledipasvir decreases as gastric pH increases. Therefore, drugs such as antacids, histamine-2 receptor antagonists, and PPIs that increase gastric pH are expected to decrease the concentration of ledipasvir. The label recommends that doses comparable to omeprazole 20 mg or lower can be administered simultaneously with the drug under fasting conditions. A similar statement is listed in the sofosbuvir/velpatasvir prescribing information, in which the solubility of velpatasvir decreases as gastric pH increases. The label states that coadministration of omeprazole or other PPIs is not recommended, but if it is medically necessary, the direct-acting antiviral should be administered with food and taken 4 hours before omeprazole 20 mg. Inform patients with hepatitis C receiving direct-acting antivirals about the potential for these agents to interact with PPIs. Tell them to avoid PPIs (both OTC and prescription agents) unless their prescriber deems them to be medically necessary.