CMV Antiviral — Viral Terminase Inhibitor (Prophylaxis in HSCT) Pregnancy: eMC §4.6: there are no data from the use of letermovir in pregnant women and studies in animals have shown reproductive toxicity; letermovir is not recommended during pregnancy or in women of childbearing potential who are not using contraception. It is unknown whether letermovir is excreted in human milk (animal data show excretion in milk) and a risk to newborns/infants cannot be excluded, so a decision must be made whether to discontinue breast-feeding or letermovir. Irreversible testicular toxicity and impairment of fertility were observed in male rats but not in male mice or monkeys.

Letermovir

Brand names: Prevymis

Letermovir is an antiviral used for prophylaxis of cytomegalovirus (CMV) reactivation and disease in CMV-seropositive adult recipients of an allogeneic haematopoietic stem cell transplant, available in oral and intravenous forms.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 480 mg once daily (reduced to 240 mg once daily if co-administered with ciclosporin)

Route: The fetched SPC is the concentrate for solution for infusion - for intravenous use only, diluted before administration and given by intravenous infusion via a peripheral or central venous catheter over approximately 60 minutes through a sterile 0.2 micron or 0.22 micron polyethersulfone (PES) in-line filter. Letermovir is also available for oral administration (240 mg film-coated tablets and 20 mg / 120 mg granules in sachet) and the formulations may be used interchangeably at the discretion of the physician

Frequency: Once daily

eMC §4.2 (PREVYMIS 240 mg concentrate for solution for infusion). Should be initiated by a physician experienced in the management of patients who have had an allogeneic haematopoietic stem cell transplant (HSCT) or a kidney transplant. The 480 mg once-daily dose applies to adult and paediatric patients weighing at least 30 kg who are HSCT recipients, and to adult and paediatric patients weighing at least 40 kg who are kidney transplant recipients. HSCT PROPHYLAXIS DURATION: start after HSCT - may be started on the day of transplant and no later than 28 days post-HSCT, before or after engraftment - and continue through 100 days post-HSCT; prolonged prophylaxis beyond 100 days may benefit some patients at high risk of late CMV reactivation; safety and efficacy beyond 200 days has not been studied. KIDNEY TRANSPLANT: start on the day of transplant and no later than 7 days post-transplant, and continue through 200 days post-transplant. CICLOSPORIN DOSE ADJUSTMENT: if co-administered with ciclosporin, decrease letermovir to 240 mg once daily; if ciclosporin is initiated after starting letermovir, decrease the next letermovir dose to 240 mg once daily; if ciclosporin is discontinued after starting letermovir, increase the next letermovir dose to 480 mg once daily; if ciclosporin dosing is temporarily interrupted because of high ciclosporin levels, no letermovir dose adjustment is needed. For paediatric patients weighing less than 30 kg receiving intravenous letermovir, the SPC states no adjustment is required for co-administered ciclosporin. MISSED DOSE: give as soon as possible; if it is time for the next dose, skip the missed dose and return to the regular schedule - do not double the next dose or give more than prescribed. ELDERLY: no dose adjustment based on age. HEPATIC IMPAIRMENT: no dose adjustment for mild (Child-Pugh A) to moderate (Child-Pugh B) impairment; not recommended in severe (Child-Pugh C) impairment; not recommended in moderate hepatic impairment combined with moderate or severe renal impairment. ADMINISTRATION: if possible, intravenous administration should not exceed 4 weeks. The diluted solution must be administered through a sterile 0.2 or 0.22 micron PES in-line filter and no other filter; the entire contents of the intravenous bag should be administered. PAEDIATRIC: the SPC gives fixed once-daily intravenous doses for HSCT recipients weighing less than 30 kg in weight bands (SPC Table 1) - obtain those bands from the SPC and a children's formulary rather than extrapolating; dose adjustment may be necessary for paediatric patients weighing less than 30 kg when switching between oral and intravenous formulations. Safety and efficacy have not been established in HSCT patients weighing less than 5 kg or in kidney transplant patients weighing less than 40 kg, and no posology recommendation can be supported for kidney transplant patients weighing less than 40 kg. US labelling (PREVYMIS, Merck Sharp & Dohme, label date 2026-01-14) agrees on 480 mg once daily orally or as an intravenous infusion over 1 hour, reduced to 240 mg once daily with cyclosporine, and states the injection should be used only in patients unable to take oral therapy, switching to oral as soon as able.

Dose adjustments

Renal

eMC §4.2: no dose adjustment of letermovir is recommended for patients with mild, moderate or severe renal impairment. No dose recommendation can be made for patients with end stage renal disease (ESRD) with or without dialysis, and efficacy and safety have not been demonstrated in ESRD. The concentrate for solution for infusion contains hydroxypropylbetadex, which could accumulate in patients with moderate or severe renal impairment (creatinine clearance less than 50 mL/min) or in young children (less than 2 years of age) - serum creatinine levels should be closely monitored in these patients. Letermovir is also not recommended in patients with moderate hepatic impairment combined with moderate or severe renal impairment.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients (eMC §4.3)
Concomitant administration with pimozide (eMC §4.3)
Concomitant administration with ergot alkaloids (eMC §4.3)
Concomitant administration with St John's wort (Hypericum perforatum) (eMC §4.3)
When letermovir is combined with ciclosporin, concomitant use of dabigatran, atorvastatin, simvastatin, rosuvastatin or pitavastatin is contraindicated (eMC §4.3)

Side effects

Nausea (7.2%) - common
Diarrhoea (2.4%) - common
Vomiting (1.9%) - common; abdominal pain - uncommon (nausea 1.6%, vomiting 0.8% and abdominal pain 0.5% were the most frequent reactions leading to discontinuation)
Hypersensitivity, decreased appetite, dysgeusia, headache and vertigo - uncommon
Alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased and muscle spasms - uncommon
Fatigue and peripheral oedema - uncommon

Interactions

Ciclosporin (eMC §4.2, §4.5) - decrease the letermovir dose to 240 mg once daily; increased monitoring of ciclosporin, tacrolimus and sirolimus is generally recommended for the first 2 weeks after starting and after stopping letermovir, and after changing the route of administration of letermovir
CYP3A substrates with narrow therapeutic ranges, e.g. alfentanil, fentanyl and quinidine (eMC §4.4) - use letermovir with caution as co-administration may increase their plasma concentrations; close monitoring and/or dose adjustment of the CYP3A substrate is recommended
Voriconazole (eMC §4.4) - letermovir is a moderate inducer of enzymes and transporters, so therapeutic drug monitoring of voriconazole is recommended
Dabigatran (eMC §4.4) - concomitant use should be avoided because of the risk of reduced dabigatran efficacy
OATP1B1/3 substrates including many statins (eMC §4.4) - letermovir may increase their plasma concentrations
US label §7.1: letermovir is a substrate of OATP1B1/3 and P-gp transporters and UGT1A1/3 enzymes; OATP1B1/3 inhibitors may increase letermovir concentrations, and co-administration with inducers of transporters (e.g. P-gp) and/or enzymes (e.g. UGTs) is not recommended. Co-administration with midazolam increases midazolam plasma concentrations (§7.2)

Clinical monograph

How it works

It inhibits the CMV DNA terminase complex, preventing the cleavage and packaging of viral DNA into mature virions, a target distinct from that of other anti-CMV agents.

Prescribing in practice

It is active only against CMV and provides no cover against other herpesviruses, so it does not replace prophylaxis directed at those pathogens.
Letermovir inhibits CYP3A and OATP1B transporters, notably increasing exposure to drugs such as ciclosporin and certain statins, requiring co-medication review and dose adjustment.
The dose is reduced when given with ciclosporin, and the oral and intravenous routes can be used interchangeably without dose change as set out in the SPC.

Monitoring

Monitor for CMV reactivation despite prophylaxis and review levels of interacting immunosuppressants such as ciclosporin and tacrolimus.

Counselling the patient

Continue prophylaxis for the full prescribed duration even if you feel well.
Report symptoms of infection promptly to your transplant team.
Do not start new medicines without checking, as several interact with this drug.

Evidence & guidelines

Efficacy in transplant CMV prophylaxis was established in a pivotal randomised placebo-controlled trial and is reflected in the SPC.

Reference: Marty et al. NEJM 2017 (HSCT letermovir trial); NICE TA568; MHRA SPC Prevymis; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways