Letermovir

PREVYMIS is an antiviral drug against CMV [see Microbiology (12.4) ] .

• PREVYMIS is a CMV DNA terminase complex inhibitor indicated for: Prophylaxis of cytomegalovirus (CMV) infection and disease in adult and pediatric patients 6 months of age and older and weighing at least 6 kg who are CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT). ( 1.1 ) Prophylaxis of CMV disease in adult and pediatric patients 12 years of age and older and weighing at least 40 kg who are kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).

• PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids: Pimozide: Concomitant administration of PREVYMIS in patients receiving pimozide may result in increased concentrations of pimozide due to inhibition of cytochrome P450 3A (CYP3A) by letermovir, which may lead to QT prolongation and torsades de pointes [see Warnings and Precautions (5.1) and Drug Interactions (7.2 , 7.3) ] . Ergot alkaloids: Concomitant administration of PREVYMIS in patients receiving ergot alkaloids may result in increased concentrations of ergot alkaloids (ergotamine and dihydroergotamine) due to inhibition of CYP3A by letermovir, which may lead to ergotism [see Warnings and Precautions (5.1) and Drug Interactions (7.2 , 7.3) ] .contraindicated

Adult and Pediatric Patients 12 Years of Age and Older and Weighing at least 30 kg Who Are HSCT Recipients or Adult and Pediatric Patients 12 Years of Age and Older and Weighing at least 40 kg Who Are Kidney Transplant Recipients: HSCT : 480 mg administered once daily orally or as an intravenous (IV) infusion over 1 hour through 100 days post-HSCT. In patients at risk for late CMV infection and disease, PREVYMIS may be continued through 200 days post-HSCT. ( 2.1 , 2.3 ) Kidney Transplant : 480 mg administered once daily orally or as an IV infusion over 1 hour through 200 days post-transplant. ( 2.1 , 2.3 ) Pediatric Patients 6 Months to Less than 12 Years of Age or 12 Years of Age and Older and Weighing Less than 30 kg Who Are HSCT Recipients: HSCT : Dosing based on weight administered once daily orally or as an IV infusion over 1 hour through 100 days post-HSCT. In patients at risk for late CMV infection and disease, PREVYMIS may be continued through 200 days post-HSCT. ( 2.1 , 2.5 ) PREVYMIS injection must be diluted prior to administration. ( 2.1 ) PREVYMIS injection must be administered through a sterile 0.2 micron or 0.22 micron polyethersulfone (PES) in-line filter. ( 2.1 , 2.10 ) Following the completion of PREVYMIS prophylaxis, monitoring for CMV reactivation in HSCT recipients is recommended. ( 2.2 ) Dosage Adjustment: If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily in adult and pediatric patients 12 years of age and older.

Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions: The concomitant use of PREVYMIS with certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug. Consult the full prescribing information for contraindications and dosage recommendations for concomitant drugs. ( 4 , 5.1 , 7.1 , 7.2 , 7.3 ) Risks Associated with Hydroxypropyl Betadex Excipient in Intravenous Formulation: Intravenous formulation of PREVYMIS contains the excipient hydroxypropyl betadex. PREVYMIS injection should be used only in patients unable to take oral therapy. If possible, intravenous administration should not exceed 4 weeks. In patients with renal impairment, accumulation of hydroxypropyl betadex may occur. Animal studies have shown the potential for hydroxypropyl betadex to cause ototoxicity. ( 5.2 , 8.6 , 13.2 ) 5.1 Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions The concomitant use of PREVYMIS and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug [see Contraindications (4) and Drug Interactions (7.1 , 7.2 , 7.3) ] . See Table 11 for steps to prevent or manage these possible or known significant drug interactions, including dosing recommendations.

Adult HSCT Patients: Most common adverse events (occurring in at least 10% of subjects in the PREVYMIS group and at a frequency at least 2% greater than placebo) are nausea, diarrhea, vomiting, peripheral edema, cough, headache, fatigue, and abdominal pain. ( 6.1 ) Adult Kidney Transplant Patients: Most common adverse event (occurring in at least 10% of subjects in the PREVYMIS group and at a frequency greater than valganciclovir) is diarrhea. ( 6.1 ) Pediatric Patients: Adverse events in pediatric patients are similar to adults. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult CMV-seropositive Recipients [R+] of an Allogeneic HSCT Prophylaxis Through Week 14 (~100 days) Post-HSCT The safety of PREVYMIS was evaluated in a Phase 3 randomized, double-blind, placebo-controlled trial (P001) in which 565 subjects were randomized and treated with PREVYMIS (N=373) or placebo (N=192) through Week 14 post-HSCT. Adverse events were those reported while subjects were on study medication or within two weeks of study medication completion/discontinuation.

Renal Impairment: Closely monitor serum creatinine levels in patients with CLcr less than 50 mL/min using PREVYMIS injection. ( 8.6 ) Hepatic Impairment: PREVYMIS is not recommended for patients with severe (Child-Pugh C) hepatic impairment. ( 8.7 ) 8.1 Pregnancy Risk Summary No adequate human data are available to establish whether PREVYMIS poses a risk to pregnancy outcomes. In animal reproduction studies, embryo-fetal developmental toxicity (including fetal malformations) was observed in rats during the period of organogenesis at letermovir exposures (AUC) 11 times higher than human exposure at the recommended human dose (RHD). In rabbits, no embryo-fetal developmental toxicity was noted at exposures that were not maternally toxic (up to letermovir exposures 2 times higher than human exposure at the RHD). In a rat pre/post-natal development study, total litter loss was observed at maternal letermovir exposures approximately 2 times higher than human exposure at the RHD (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Metabolism

The pharmacokinetic properties of letermovir are displayed in Table 12. Table 12: Absorption, Distribution, Metabolism, Elimination (ADME), and Pharmacokinetic Properties of PREVYMIS Values were obtained in studies of healthy adult subjects unless otherwise indicated.

There is no specific antidote for overdose with PREVYMIS. In case of overdose, it is recommended that the patient be monitored for adverse reactions and appropriate symptomatic treatment be instituted. It is unknown whether dialysis will result in meaningful removal of PREVYMIS from systemic circulation.

• Nov 8, 2017NDANDA209939Merck Sharp Dohme
• Nov 8, 2017NDANDA209940Merck Sharp Dohme
• Aug 30, 2024NDANDA219104Msd

1. 1Off Label Use65722%
2. 2Drug Ineffective2699.0%
3. 3Cytomegalovirus Infection Reactivation2307.7%
4. 4Death1846.2%
5. 5Cytomegalovirus Infection1705.7%
6. 6Acute Kidney Injury1685.6%
7. 7Drug Interaction1585.3%
8. 8Product Use In Unapproved Indication1505.0%
9. 9Pancytopenia1414.7%
10. 10Drug Resistance953.2%
11. 11Cytomegalovirus Viraemia933.1%
12. 12Cystitis Haemorrhagic893.0%
13. 13Hospitalisation872.9%
14. 14Pyrexia872.9%
15. 15Bk Virus Infection862.9%

The 10 most recently updated of 56 ClinicalTrials.gov registrations naming Letermovir as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Clinical Study of Letermovir (MK-8228) in Children and Adolescents Who Receive a Kidney Transplant (KT) (MK-8228-077)
  Recruiting · Phase 1 · Interventional · 40 enrolled · Merck Sharp & Dohme LLC
  NCT07199465updated 2026-06-12
• Letermovir (Prevymis) for CMV in Kidney and Pancreas Transplant Recipients
  Recruiting · Phase 3 · Interventional · 90 enrolled · University of Wisconsin, Madison
  NCT06407232updated 2026-06-11
• Open Label Trial of Oral Letermovir for CMV Prophylaxis in Thoracic Transplant Recipients
  Recruiting · Phase 2 · Interventional · 80 enrolled · University of Pennsylvania
  NCT06066957updated 2026-06-03
• The Use of Cytomegalovirus Cell Mediated Immunity to Optimize the Duration of Letermovir Prophylaxis in Hematopoietic Cell Transplant Recipients
  Recruiting · Interventional · 105 enrolled · M.D. Anderson Cancer Center
  NCT06639854updated 2026-06-02
• Letermovir Prophylaxis Duration Guided by CMV-Specific T-cell Monitoring After Allo-HSCT.
  Recruiting · Phase 4 · Interventional · 120 enrolled · WeiShi
  NCT07569653updated 2026-06-01
• A Safety Assessment of Oral Letermovir in Infants With Symptomatic Congenital Cytomegalovirus
  Recruiting · Phase 1 · Interventional · 12 enrolled · National Institute of Allergy and Infectious Diseases (NIAID)
  NCT06118515updated 2026-05-22
• Letermovir vs Valganciclovir in CMV R+ Kidney Transplant
  Not yet recruiting · Phase 4 · Interventional · 300 enrolled · Elisabeth Kincaide
  NCT07571135updated 2026-05-08
• A Study of the Drug Letermovir as Prevention of Cytomegalovirus Infection After Stem Cell Transplant in Pediatric Patients
  Recruiting · Phase 3 · Interventional · 105 enrolled · Children's Oncology Group
  NCT05711667updated 2026-05-05
• Letermovir for CMV Prevention After Lung Transplantation
  Completed · Phase 2 · Interventional · 15 enrolled · Fernanda P Silveira, MD, MS
  NCT05041426updated 2026-04-09
• De-novo Initiation of Letermovir vs Valganciclovir for Cytomegalovirus Prophylaxis in AA Kidney Transplant Recipients
  Active not recruiting · Phase 3 · Interventional · 30 enrolled · Virginia Commonwealth University
  NCT06001320updated 2026-04-01

Frequently asked questions

How does Letermovir work?

PREVYMIS is an antiviral drug against CMV [see Microbiology (12.4) ] .

What is Letermovir used for?

According to FDA labeling, Letermovir carries indications including: PREVYMIS is a CMV DNA terminase complex inhibitor indicated for: Prophylaxis of cytomegalovirus (CMV) infection and disease in adult and pediatric patients 6 months of age and older and weighing at least 6 kg who are CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT). ( 1.1 ) Prophylaxis of CMV disease in adult and pediatric patients 12 years of age and older and weighing at least 40 kg who are kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Letermovir?

Letermovir is classified as Other antivirals, Cytomegalovirus DNA Terminase Complex Inhibitor, ATP-Binding Cassette (ABC) Transporter Interactions, Cytochrome P450 2B6 Inducers, Cytochrome P450 2C19 Inducers, Cytochrome P450 2C8 Inhibitors, Cytochrome P450 2C9 Inducers, Cytochrome P450 3A Inhibitors, Cytochrome P450 3A4 Inhibitors, Cytochrome P450 3A5 Inhibitors, DNA Terminase Complex Inhibitors, Organic Anion Transporting Polypeptide 1B1 Inhibitors, Organic Anion Transporting Polypeptide 1B3 Inhibitors, Decreased DNA Replication.

What are the brand names for Letermovir?

Letermovir is marketed under brand names including Prevymis.

What are the contraindications for Letermovir?

Letermovir labeling lists contraindications including: PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids: Pimozide: Concomitant administration of PREVYMIS in patients receiving pimozide may result in increased concentrations of pimozide due to inhibition of cytochrome P450 3A (CYP3A) by letermovir, which may lead to QT prolongation and torsades de pointes [see Warnings and Precautions (5.1) and Drug Interactions (7.2 , 7.3) ] . Ergot alkaloids: Concomitant administration of PREVYMIS in patients receiving ergot alkaloids may result in increased concentrations of ergot alkaloids (ergotamine and dihydroergotamine) due to inhibition of CYP3A by letermovir, which may lead to ergotism [see Warnings and Precautions (5.1) and Drug Interactions (7.2 , 7.3) ] .. Always consult the full prescribing information and a clinician.