Omeprazole and Velpatasvir: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Omeprazole
Velpatasvir
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Velpatasvir is part of a hepatitis C treatment (often combined with sofosbuvir). It needs a certain amount of stomach acid to dissolve and get absorbed properly. Omeprazole is an acid reducer, so it can lower how much velpatasvir your body takes in. That matters because if your body absorbs less of the medicine, your hepatitis C treatment may not work as well.
The good news is your care team can manage this. They may keep the omeprazole dose low and space out when you take each medicine, or choose a different plan. Please don't stop or change either medicine on your own. Just talk with your pharmacist or doctor so they can set up the safest timing for you.
Effect: Decreased velpatasvir exposure with potential loss of antiviral efficacy.
Mechanism: Velpatasvir solubility is pH-dependent; omeprazole-induced gastric pH elevation reduces dissolution and absorption. This is a PK (absorption) interaction, not enzyme-mediated. Neither agent is a prodrug relevant here.
- Direction: Reduced velpatasvir effect (treatment failure risk).
- Severity/Evidence: Major; theoretical basis.
- Onset: Unspecified.
Management: Concurrent use not recommended. If a PPI is required, limit omeprazole to 20 mg/day and give sofosbuvir/velpatasvir with food at least 4 hours before omeprazole. Monitor virologic response.
What happens
Decreased velpatasvir exposure
Interaction Deep Dive
Using velpatasvir together with this drug is not advised, because doing so may lower velpatasvir exposure and could lead to reduced efficacy. When a proton pump inhibitor cannot be avoided, omeprazole may be administered at a dose no greater than 20 mg12. The sofosbuvir/velpatasvir combination should be taken with food and given at least 4 hours before omeprazole2.
Why it happens (mechanism)
Decreased velpatasvir solubility due to pH increases
How to manage this interaction
The main concern is that omeprazole may reduce how much velpatasvir gets absorbed, which could weaken your hepatitis C treatment. Here is what typically helps:
- Keep taking both as prescribed unless your care team tells you otherwise.
- Your team may keep the omeprazole dose at or below 20 mg per day.
- Timing matters: take sofosbuvir/velpatasvir with food, at least 4 hours before your omeprazole dose.
- Your team may choose a different acid-reducing option if one is possible.
Ask your pharmacist or prescriber to confirm the best dose and schedule for you, and mention any acid reflux medicines you take, including over-the-counter ones.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In pharmacokinetic studies, giving omeprazole 20 mg once daily 2 hours before sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg produced a 57% reduction in velpatasvir Cmax and a 54% reduction in AUC. When given 4 hours after sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg, velpatasvir Cmax and AUC both fell by 51% 1.
b) In drug interaction studies, administering omeprazole 20 mg at the same time as velpatasvir 100 mg produced a 37% reduction in velpatasvir Cmax and a 36% reduction in AUC. Dosing 12 hours before velpatasvir led to decreases of 57% and 55%. Dosing 2 hours before velpatasvir led to a 48% decrease and a 38% decrease. Dosing 4 hours after velpatasvir led to a 33% and 26% decrease 3.
Common questions
Can I take Omeprazole and Velpatasvir together?
Omeprazole can lower velpatasvir absorption and may reduce how well your hepatitis C treatment works, so this combination is generally avoided. If a PPI is needed, your care team can keep omeprazole at 20 mg or less and have you take velpatasvir with food at least 4 hours beforehand. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Velpatasvir interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Omeprazole and Velpatasvir interaction managed?
The main concern is that omeprazole may reduce how much velpatasvir gets absorbed, which could weaken your hepatitis C treatment. Here is what typically helps: Keep taking both as prescribed unless your care team tells you otherwise. Your team may keep the omeprazole dose at or below 20 mg per day. Timing matters: take sofosbuvir/velpatasvir with food, at least 4 hours before your omeprazole dose.… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Omeprazole or Velpatasvir need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (3)
- Product Information: VOSEVI(TM) oral tablets, sofosbuvir velpatasvir voxilaprevir oral tablets. Gilead Sciences Inc (per manufacturer), Foster City, CA, 2017. DailyMed
- Product Information: EPCLUSA(R) oral tablets, sofosbuvir velpatasvir oral tablets. Gilead Sciences, Inc (per manufacturer), Foster City, CA, 2017. DailyMed
- Product Information: EPCLUSA(R) oral tablets, sofosbuvir velpatasvir oral tablets. Gilead Sciences Inc (per FDA), Foster City, CA, 2016. DailyMed
Keep reading about Omeprazole
Keep reading about Velpatasvir
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