Midazolam and Letermovir Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Midazolam
No brand names on recordLetermovir 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 midazolam exposure and increased risk for prolonged sedation
Interaction Deep Dive
Concomitant use of midazolam (CYP3A4 substrate) with this drug (moderate CYP3A4 inhibitor) may result in prolonged sedation because of a decrease in plasma clearance of midazolam and should be avoided. Concomitant use of midazolam with moderate CYP3A4 inhibitors has reduced midazolam clearance and increased its half-life in pharmacokinetic studies1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated midazolam metabolism
Literature reports
3 reports — tap to read
a) Concomitant administration of a single dose of midazolam 0.5 mg/kg IV (CYP3A4 substrate) and erythromycin 500 mg 3 times a day (moderate CYP3A4 inhibitor), for 1 week (n=6), reduced the clearance of midazolam and doubled the half-life 1.
b) In a 3-way crossover study (n=9) concomitant administration of midazolam (CYP3A4 substrate), diltiazem 60 mg 3 times a day, and verapamil 80 mg 3 times a day (moderate CYP3A4 inhibitors) increased the half-life of midazolam from 5 to 7 hours. No interaction was observed in healthy subjects between midazolam and nifedipine 1.
c) In a clinical study, the concurrent administration of letermovir and oral midazolam in healthy women (n=16) increased midazolam mean Cmax by 172.4% and mean AUC(0 to last measurable concentration) by 225.3%. Similarly, the concurrent administration of letermovir and IV midazolam led to increases in midazolam mean Cmax by 105.2% and mean AUC(0 to last measurable concentration) by 146.6%. Participants received oral letermovir 240 mg on days 1 to 6. A single bolus of IV midazolam 1 mg/mL was administered on day 4 alone and immediately after letermovir on day 4. Oral midazolam 1 mL was administered on the morning of day 2 alone and immediately after letermovir on day 6. Letermovir is an inhibitor of CYP3A, while midazolam is a substrate of CYP3A. Clearance for midazolam was decreased in the presence of letermovir compared with midazolam alone. If letermovir and midazolam are coadministered, frequent monitoring and possible dose adjustments may be needed during and after discontinuation of letermovir 2.
Common questions
Can I take Midazolam and Letermovir Injection together?
Increased midazolam exposure and increased risk for prolonged sedation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Midazolam 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Midazolam 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 (2)
- Product Information: NAYZILAM(R) nasal spray, midazolam nasal spray. Proximagen LLC (per FDA), Plymouth, MN, 2019. DailyMed
- Kropeit D, McCormick D, Erb-Zohar K, et al: Pharmacokinetics and safety of Letermovir and Midazolam coadministration in healthy subjects. Clin Pharmacol Drug Dev 2022; 11(1):16-24. PubMed
Keep reading about Midazolam
Keep reading about Letermovir Injection
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