Omeprazole and Ledipasvir: 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
Ledipasvir
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.
You're taking omeprazole (a stomach acid reducer) along with ledipasvir, part of your hepatitis C treatment. Here's the key point: ledipasvir only dissolves well when your stomach is acidic. Because omeprazole lowers stomach acid, it can make your body absorb less ledipasvir. That matters because getting enough of the medicine is what clears the virus, so weaker absorption could mean the treatment doesn't work as well.
The good news is this is very manageable. Studies showed that taking both at the same time, on an empty stomach, avoided the problem. Please don't change anything on your own, but do talk with your pharmacist or doctor about the best timing.
Effect: Reduced ledipasvir exposure with potential loss of antiviral efficacy.
Mechanism: Ledipasvir solubility is pH-dependent; omeprazole raises gastric pH, decreasing dissolution and absorption. Neither drug is a prodrug here; this is a purely absorption-based PK interaction.
Magnitude/evidence: Theoretical basis, but supported by PK data (N=33): omeprazole 20 mg given 2 h before ledipasvir reduced Cmax ~48% and AUC ~42%; simultaneous administration showed no significant reduction. Two transplant case reports showed maintained SVR.
- Limit PPI to a dose comparable to omeprazole 20 mg/day or lower.
- Administer PPI simultaneously with ledipasvir/sofosbuvir under fasted conditions.
- Monitor virologic response.
What happens
Decreased ledipasvir exposure and loss of efficacy
Interaction Deep Dive
Exercise caution when ledipasvir/sofosbuvir is given together with proton pump inhibitors, since reduced ledipasvir exposure and a resulting loss of efficacy can occur. Two drug interaction studies (N=33) demonstrated notable reductions in ledipasvir Cmax (48%) and AUC (42%) when omeprazole 20 mg/day was taken 2 hours prior to ledipasvir; these decreases were not seen with simultaneous dosing 1. In two case reports involving liver-transplant patients, restarting a proton pump inhibitor after initiating ledipasvir/sofosbuvir led to resolution of a duodenal ulcer while maintaining sustained virologic response 2. When coadministration cannot be avoided, administer the proton pump inhibitor at the same time as the ledipasvir/sofosbuvir dose, under fasted conditions, and at a dose equivalent to or lower than omeprazole 20 mg/day 1.
Why it happens (mechanism)
Loss of ledipasvir solubility due to increased pH
How to manage this interaction
Keep taking both medicines as prescribed, and let your care team guide the details. This interaction is very manageable with timing and dosing:
- Timing matters: Studies found no significant drop in ledipasvir when the PPI was taken at the same time, not hours before. Your team may recommend taking them together.
- Empty stomach: Both were best taken under fasted conditions.
- Dose: Your team may keep the omeprazole at 20 mg per day or lower.
Talk with your pharmacist or prescriber before starting, stopping, or changing either medicine, and ask them to confirm the best schedule for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) Two case reports described liver-transplant patients who stopped proton pump inhibitors (either lansoprazole or rabeprazole) when ledipasvir/sofosbuvir was started to prevent hepatitis C virus reinfection, and who then developed hemorrhagic duodenal ulcers. Restarting a proton pump inhibitor, esomeprazole 20 mg/day in both cases, led to improvement of the ulcer without any loss of sustained virologic response (SVR). Hepatitis C virus RNA was negative at 8 and 4 weeks, and both patients achieved an SVR 12 weeks after treatment ended 2.
b) In two drug interaction studies (N=33), giving a single ledipasvir 90-mg dose together with omeprazole 20 mg/day did not significantly change ledipasvir Cmax or AUC. In contrast, administering omeprazole 20 mg/day 2 hours before a single 30-mg dose of ledipasvir produced significant reductions in ledipasvir Cmax (48%) and AUC (42%) 1.
Common questions
Can I take Omeprazole and Ledipasvir together?
Omeprazole can lower ledipasvir absorption and weaken hepatitis C treatment, but taking them at the same time on an empty stomach, with the omeprazole at 20 mg per day or less, avoids most of the problem. Confirm timing with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Ledipasvir 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 Ledipasvir interaction managed?
Keep taking both medicines as prescribed, and let your care team guide the details. This interaction is very manageable with timing and dosing: Timing matters: Studies found no significant drop in ledipasvir when the PPI was taken at the same time, not hours before. Your team may recommend taking them together. Empty stomach: Both were best taken under fasted conditions. Dose: Your team may keep t… 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 Ledipasvir 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 (2)
- Product Information: HARVONI(R) oral tablets, ledipasvir sofosbuvir oral tablets. Gilead Sciences, Inc. (per manufacturer), Foster City, CA, 2014. DailyMed
- Miuma S, Miyaaki H, Miyazoe Y, et al: Development of duodenal ulcers due to the discontinuation of proton pump inhibitors after the induction of sofosbuvir plus ledipasvir therapy: a report of two cases. Transplant Proc 2018; 50(1):222-225. PubMed
Keep reading about Omeprazole
Keep reading about Ledipasvir
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