What is the potential drug interaction between VELASOF (Sofosbuvir) / SOVIHEP V (Velpatasvir) and a proton pump inhibitor (PPI)?

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Last updated: April 15, 2025View editorial policy

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From the Guidelines

Velasof/Sovihep V (sofosbuvir/velpatasvir) can be affected by proton pump inhibitors (PPIs), and caution is advised when using them together, with a recommendation to take Velasof/Sovihep V with food and separate the PPI dose by at least 4 hours, with the PPI dose not exceeding the equivalent of omeprazole 20mg daily 1. This interaction occurs because PPIs increase gastric pH, which can reduce the absorption of velpatasvir, potentially decreasing its effectiveness against hepatitis C virus. Some key points to consider when managing this interaction include:

  • The solubility of velpatasvir decreases as pH increases, which is why PPIs can affect its absorption 1.
  • For most patients, proton pump inhibitors should be avoided during sofosbuvir/velpatasvir treatment, but if considered necessary, the dose should be maximized at a comparable level to omeprazole 20 mg and taken 4 hours after Velasof/Sovihep V administration 1.
  • If possible, consider using H2-receptor antagonists (like famotidine 40mg twice daily) or antacids instead, ensuring they're separated from Velasof/Sovihep V by at least 4 hours 1. This approach helps maintain the efficacy of the hepatitis C treatment while managing acid-related conditions. Patients should not discontinue their PPI without medical consultation but should discuss with their healthcare provider how to optimize the timing of both medications to minimize interaction risks. It is also important to note that sofosbuvir/velpatasvir may be given with most antiretroviral drugs, with some exceptions, and may increase tenofovir exposure due to P-gp inhibition, requiring monitoring for renal adverse events 1.

From the Research

Drug Interaction with Proton Pump Inhibitor

  • The interaction between VELASOF/SOVIHEP V and proton pump inhibitors (PPIs) has been studied in the context of treating chronic hepatitis C virus (HCV) infection 2.
  • A retrospective cohort study found no statistically significant association between PPI use and lower sustained virologic response (SVR) in patients treated with sofosbuvir/velpatasvir (SOF/VEL) for chronic HCV infection 2.
  • The study adjusted for variables such as African-American race, presence of cirrhosis, prior treatment, BMI greater than 30 kg/m2, and HCV genotype, and found that concomitant PPI treatment did not significantly impact the success or failure of SOF/VEL treatment 2.

Mechanism of Action and Efficacy

  • Sofosbuvir/velpatasvir is a direct-acting antiviral (DAA) combination that targets the NS5A and NS5B proteins of the HCV virus, providing a pangenotypic treatment option for HCV infection 3, 4.
  • The combination has been shown to be effective in achieving high sustained virological response (SVR) rates in patients with HCV genotypes 1-6, including those with compensated cirrhosis and prior treatment failures 3, 4.

Comparison with Other Therapies

  • A systematic review compared the use of PPIs and H2 receptor antagonists (H2RAs) in patients on dual antiplatelet therapy for coronary artery disease, and found that PPIs were superior to H2RAs in preventing gastrointestinal complications, but were associated with a higher risk of high on-treatment platelet reactivity 5.
  • A real-world effectiveness study of sofosbuvir/velpatasvir/voxilaprevir in DAA-experienced patients found high SVR rates across all genotypes, including those with prior NS5A experience 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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