Letermovir Injection and Tacrolimus: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Tacrolimus
Letermovir Injection
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 tacrolimus exposure and an increased risk of toxicity
Interaction Deep Dive
Coadministration of letermovir and tacrolimus increased the tacrolimus AUC and Cmax by 142% and 57%, respectively1. Concomitant use of tacrolimus and letermovir may increase tacrolimus whole blood trough concentrations and the risk of serious toxicity (eg, neurotoxicity, QT prolongation). If concomitant use is required, decrease the tacrolimus dose and adjust based on whole blood trough concentrations. A rapid, sharp rise in tacrolimus levels may occur early, despite an immediate reduction of tacrolimus dose. Monitor whole blood trough concentrations early and frequently; start within 1 to 3 days and continue as necessary 2. Following discontinuation of letermovir, monitor tacrolimus whole blood concentrations and adjust tacrolimus dose as necessary 1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of tacrolimus
Literature reports
4 reports — tap to read
a) In a retrospective study in allogeneic hematopoietic cell transplantation recipients (N=35) who had been taking tacrolimus for at least 5 days before initiating letermovir the median percent increase in tacrolimus concentration-to-dose ratio from baseline to days 2 to 4 was 22%, days 5 to 7 was 47%, days 8 to 11 was 66%, and days 12 to 14 was 81% after letermovir initiation. The mean frequency of tacrolimus dose adjustments over the 14-day period after initiation of letermovir on days 2 to 4, days 5 to 7, days 8 to 11, and days 12 to 14 was 0.66, 0.69, 1.06 and 0.57, respectively. The median change in tacrolimus dose from baseline was 0% on days 2 to 4, -12.5% on days 5 to 7, and -25% days 8 to 11 and on days 12 to 14 following letermovir initiation. The median age of patients was 59 years (range, 19 to 71 years), 46% were male, and 71% experienced mucositis within 7 days after letermovir initiation with the median highest grade being 1.5 (range, 0 to 4) 3.
b) Mean tacrolimus AUC and Cmax increased by 142% and 57% respectively, following a single 5-mg oral dose given concomitantly with letermovir 480 mg 1.
c) Mean sirolimus AUC and Cmax increased by 66% and 176% following a single 2 mg oral dose given concomitantly with letermovir 480 mg 1.
d) In an another drug interaction study, coadministration of letermovir (oral 240 mg once daily) with a CYP3A substrate, midazolam (1 mg single dose IV) led to increased AUC, Cmax and C24hr of midazolam by 47%, 5% and 174%, respectively. And, coadministration of letermovir (oral 240 mg once daily) with midazolam (2 mg single dose orally) led to increased AUC and Cmax of midazolam by 125% and 72%, respectively 1.
Common questions
Can I take Letermovir Injection and Tacrolimus together?
Increased tacrolimus exposure and an increased risk of toxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Letermovir Injection and Tacrolimus interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Letermovir Injection or Tacrolimus 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: PREVYMIS(R) oral tablets, oral pellets, intravenous injection, letermovir oral tablets, oral pellets, intravenous injection. Merck Sharp & Dohme Corp (per FDA), Rahway, NJ, 2024. DailyMed
- Product Information: PROGRAF(R) oral capsules, oral granules for suspension, intravenous injection, tacrolimus oral capsules, oral granules for suspension, intravenous injection. Astellas Pharma US Inc (per FDA), Northbrook, IL, 2023. DailyMed
- Marciano KA, Seago K, Dillaman M, et al: Evaluation of the pharmacokinetic interaction between letermovir and tacrolimus in allogeneic hematopoietic cell transplantation recipients. Transplant Cell Ther 2022; 28(7):371.e1-371.e4. PubMed
Keep reading about Tacrolimus
Keep reading about Letermovir Injection
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