Tolvaptan and Letermovir Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Letermovir Injection
Tolvaptan
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.
What happens
Increased tolvaptan exposure
Interaction Deep Dive
Coadministration of tolvaptan, a CYP3A substrate, with fluconazole, a moderate CYP3A inhibitor, resulted in a 200% increase in tolvaptan AUC4 resulting in significant increase in adverse reactions associated with tolvaptan, particularly significant diuresis, dehydration, and acute renal failure. If tolvaptan and fluconazole are concomitantly administered, the tolvaptan dose should be reduced and the patient should be frequently monitored for any adverse reactions associated with tolvaptan 2. Avoid concomitant use of tolvaptan with moderate CYP3A inhibitors when tolvaptan is being used to treat hyponatremia 1. When tolvaptan is being used to slow the decline in kidney function in patients with autosomal dominant polycystic kidney disease, reduce dose of tolvaptan if used concomitantly with moderate CYP3A inhibitors. For patients taking tolvaptan 90 mg in the morning and 30 mg in the afternoon, reduce dose to 45 mg and 15 mg, respectively. For those taking 60 mg in the morning and 30 mg in the afternoon, reduce dose to 30 mg and 15 mg. For those taking 45 mg in the morning and 15 mg in the afternoon, reduce to 15 mg for both doses. If the initial dose reduction is not tolerated, consider reducing the dose further. If reduced doses are not available, consider temporary interruption of tolvaptan for short-term therapy with a moderate CYP3A inhibitor 3.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of tolvaptan
Literature reports
1 report — tap to read
a) Tolvaptan AUC and Cmax were increased by 200% and 80% when fluconazole 400 mg was given one day before tolvaptan followed by fluconazole 200 mg concomitantly with tolvaptan 4.
Common questions
Can I take Tolvaptan and Letermovir Injection together?
Increased tolvaptan exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tolvaptan and Letermovir Injection 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 strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Tolvaptan or Letermovir Injection 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 (4)
- Product Information: SAMSCA(R) oral tablets, tolvaptan oral tablets. Otsuka America Pharmaceutical Inc (per FDA), Rockville, MD, 2021. DailyMed
- Product Information: DIFLUCAN(R) oral tablets, suspension, fluconazole oral tablets, suspension. Roerig (per FDA), New York, NY, 2023. DailyMed
- Product Information: JYNARQUE(R) oral tablets, tolvaptan oral tablets. Otsuka America Pharmaceutical Inc (per manufacturer), Rockville, MD, 2020. DailyMed
- Product Information: JYNARQUE(TM) oral tablets, tolvaptan oral tablets. Otsuka America Pharmaceutical Inc (per manufacturer), Rockville, MD, 2018. DailyMed
Keep reading about Letermovir Injection
Keep reading about Tolvaptan
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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