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IV PPIs and H2 antagonists did not thwart
response to ledipasvir or velpatasvir
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20th International Workshop on Clinical Pharmacology of HIV, Hepatitis & Other Antiviral Drugs. May 14-16, 2019. Noordwijk, the Netherlands
Mark Mascolini
A short course of intravenous (IV) proton pump inhibitors (PPIs) or histamine H2 antagonists did not impair virologic response to ledipasvir or velpatasvir regimens in 11 people with cirrhosis [1]. Because of the small size of this study, Researchers from the Centre Hospitalier de l'Universite de Montreal (CHUM) called for further research exploring potential interactions between these direct-acting antivirals (DAAs) and gastric acid agents.
Oral PPIs or H2 antagonists can lower concentrations of ledipasvir and velpatasvir, but the clinical impact of acid-reducing drugs on DAAs is complex. Oral PPIs can affect sustained virologic response (SVR) to sofosbuvir/ledipasvir [2,3] but apparently not to sofosbuvir/velpatasvir [4,5]. Until this study, no research explored clinical outcomes with DAAs in people receiving IV acid suppressants. The CHUM researchers aimed to address this issue in hospital patients receiving an IV acid suppressant while taking ledipasvir or velpatasvir.
This retrospective analysis involved HCV-infected people in MONTREAL-C, a single-center cohort taking an interferon-free DAA regimen and admitted to the hospital in the course of HCV treatment. The researchers focused on those receiving IV acid suppressants--either PPIs or H2 antagonists--during their hospital stay while completing an HCV regimen containing ledipasvir or velpatasvir. The outcome of interest was sustained virologic response 12 weeks after HCV therapy stopped (SVR12).
Eleven people who had 12 hospital stays included 8 men (73%), all with cirrhosis and 6 (54.5%) with decompensated cirrhosis. Median age stood at 58 years (interquartile range [IQR] 53 to 59). Seven people had HCV genotype 1a, 2 had genotype 1b, and 1 each had genotype 3 or 4. Nine people took ledipasvir/sofosbuvir with or without ribavirin and 2 took velpatasvir/sofosbuvir.
Six people received a PPI, all of them high-dose pantoprazole continuous infusion (40- to 80-mg bolus followed by 8 mg/hour continuous therapy). High-dose continuous infusion of pantoprazole lasted a median of 13.1 hours (IQR 7.3 to 16.7). Five people took the H2 antagonist famotidine at an IV dose of 20 mg every 12 hours for a median of 3 doses (IQR 2 to 3). When IV therapy stopped, 9 people took long-term oral PPIs, 1 took oral H2 antagonists, and 1 took both.
Ten of 11 people (90.9%) achieved SVR12. The only DAA failure involved a person with HCV genotype 3 who stopped velpatasvir/sofosbuvir at week 3 after suspected nonadherence and a need to complete long-term treatment of esophagitis with high-dose oral acid suppressants.
The Montreal team concluded that SVR rates were high with these DAA regimens despite a potentially clinically relevant drug-drug interaction. (They did not have pharmacokinetic data because of the retrospective nature of the study.) The researchers noted that high-dose pantoprazole typically maintains gastric pH above 5.0 and so may reduce ledipasvir or velpatasvir solubility and absorption. But the course of both IV antacid regimens was probably too short to affect DAA success. The investigators proposed that people receiving IV antacid drugs should continue their HCV therapy.
References
1. Verreault V, Trudeau C, Arbour P, et al. Short-term intravenous proton pump inhibitors and histamine H2 antagonists do not negatively affect sustained virologic response in hepatitis C cirrhotic patients treated with ledipasvir or velpatasvir containing antiviral regimens: a case series. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis & Other Antiviral Drugs. May 14-16, 2019. Noordwijk, the Netherlands. Abstract 42.
2. Terrault NA, Zeuzem S, Di Bisceglie AM, et al. Effectiveness of ledipasvir-sofosbuvir combination in patients with hepatitis C virus infection and factors associated with sustained virologic response. Gastroenterology. 2016;151:1131-40 e5.
3. Tapper EB, Bacon BR, Curry MP, et al. Evaluation of proton pump inhibitor use on treatment outcomes with ledipasvir and sofosbuvir in a real-world cohort study. Hepatology. 2016;64:1893-1899.
4. Curry MC, Bacon BR, Flamm SL, et al. Preferences in clinical practice with glecaprevir/pibrentasvir (GLE-PIB), ledipasvir/sofosbuvir (LDF-SOF), and sofosbuvir/velpatasvir (SOF-VEL); data from the TRIO Network. AASLD 2018, November 9-13, San Francisco. Abstract 678.
5. Esteban-Mur R, Agarwal K, Calleja JL, et al. Sofosbuvir/velpatasvir is effective and safe in patients with concomitant proton pump inhibitor use in clinical studies. AASLD 2018, November 9-13, San Francisco. Abstract 702.
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