Letermovir
Anti-herpesvirus agents
Anti-herpesvirus agents
An antiviral that prevents cytomegalovirus (CMV) disease after stem-cell or kidney transplants. It blocks the enzyme that packages viral DNA.
Quick facts
- Group
- Anti-herpesvirus agents
- Target
- CMV DNA terminase complex (pUL56 subunit)
- Used for
- Prevention of CMV infection
- Key effects
- Nausea · Abdominal pain · Swelling of the arms or legs
- Monitor
- CMV DNA in blood during prophylaxis
- ATC
- J05AX18
No doses: the clinician sets them by the current guideline.
Mechanism of action
Letermovir inhibits the CMV DNA terminase complex (pUL56 and pUL89 subunits). This enzyme cuts the long chains of newly made viral DNA into single genomes and packs them into capsids. Without it, infectious virions are not formed. Because it does not act on the viral DNA polymerase, letermovir stays active against CMV resistant to ganciclovir, foscarnet or cidofovir, and resistance arises through changes in pUL56.
- CMV copies its DNA as long chains
- The terminase cuts the chains into single genomes
- Letermovir blocks the terminase (pUL56)
- Genomes are not packed into capsids
Indications
- Prevention of CMV infection and disease in CMV-seropositive recipients of an allogeneic haematopoietic stem-cell transplant Cytomegalovirus infection →
- Prevention of CMV disease in kidney transplant recipients at high risk Cytomegalovirus infection →
Adverse effects
Common
- Nausea, vomiting and diarrhoea
- Abdominal pain
- Swelling of the arms or legs
- Headache, tiredness and cough
Contraindications
- Hypersensitivity to letermovir
- Combinations that its CYP3A or transporter inhibition makes unsafe (checked against the label before starting)
Key interactions
- Ciclosporin
- Raises letermovir exposure (it blocks liver uptake via OATP1B1/3); the regimen is adjusted
- CYP3A and CYP2C8 substrates
- Letermovir raises their levels; narrow-margin drugs are monitored
- St John's wort
- Listed as interacting; avoided unless discussed with the team
- Omeprazole
- Listed as interacting in patient information; reviewed before combining
What is monitored
- CMV DNA in blood during prophylaxis
- Ciclosporin and other immunosuppressant levels when combined
- Heart rhythm symptoms
- Kidney and liver function
Administration and safety
- Tablets are swallowed whole; pellets are mixed with soft food or given through a feeding tube
- The intravenous form is diluted and infused slowly, and used only while oral intake is not possible
- Started after the transplant and continued for a set period of prophylaxis
Pregnancy and breastfeeding
Human data are limited; the transplant team weighs benefit and risk.
Nursing care
- Reconcile every medicine, especially immunosuppressants, before starting
- Check transplant drug levels after starting or stopping letermovir
- Teach to report palpitations, chest pain, shortness of breath or dizziness
- Explain that CMV blood tests continue during prophylaxis
Pharmacokinetics
- Absorption
- Oral (tablets or pellets) with variable absorption; an intravenous form exists for those who cannot take it by mouth
- Metabolism
- Moderate CYP3A inhibitor; it also inhibits liver uptake transporters (OATP1B1/3) and several efflux transporters
- Elimination
- Exposure rises more than in proportion to the dose and changes over time
Test yourself
Think of the answer, then tap the question to see it.
Which viral enzyme does letermovir inhibit?
The CMV DNA terminase complex (pUL56/pUL89), which cuts and packages viral genomes.
Why is letermovir preferred over ganciclovir for prophylaxis after stem-cell transplant?
It prevents CMV infection without the bone marrow suppression of ganciclovir, which would harm a new graft.
Is letermovir active against ganciclovir-resistant CMV with DNA polymerase mutations?
Yes. It acts on the terminase, not the DNA polymerase.
Why does ciclosporin change letermovir exposure?
Ciclosporin inhibits the liver uptake transporters OATP1B1/3, so letermovir levels rise.
Connections
← Back to the class: Anti-herpesvirus agents
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Letermovir: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Letermovir Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.