II. Indications
- CMV Prophylaxis in CMV positive Hematopoietic Stem Cell Transplant recipients
III. Mechanism
- Non-Nucleoside, 3,4-dihydroquinazolinyl acetic acid
- Competive inhibitor of pUL56 subunit of the viral terminase complex of Cytomegalovirus (CMV)
- On binding pUL56, Letermovir blocks division of viral DNA in monomeric genome length DNA
- Blocks DNA processing and packaging into procapsids, thereby preventing CMV replication
IV. Dosing
- Give 480 mg IV over 1 hour or orally once daily
- Decrease dose to 240 mg daily if coadministered with Cyclosporine (and monitor Cyclosporine levels)
- Start within 28 days of transplant and continue until day 100 post-transplant
V. Adverse Effects
- Not associated with nephrotoxicity or Neutropenia (Unlike other CMV agents)
- Nausea and Vomiting
- Diarrhea
- Abdominal Pain
- Cough
- Headache
- Fatigue
- Cardiac Dysrhythmias (Tachycardia, Atrial Fibrillation)
VI. Safety
- Avoid in pregnancy
- Unknown safety in Lactation
VII. Pharmacokinetics
- Excreted in the feces
- No dosage adjustment in Creatinine Clearance (CrCl) >10 ml/min
- Unknown safety in CrCl <10 ml/min or Hemodialysis
- No dosage adjustment in mild to moderate hepatic Impairment (Child-Pugh A or B)
- Contraindicated in severe hepatic Impairment (Child-Pugh C)
VIII. Drug Interactions
- Letermovir is a moderate CYP3A4 Inhibitor
- Avoid with ergot alkaloids or Pimozide
- Letermovir is a substrate of OATP1B1/3
- Modify Statins (increases Statin levels)
- Avoid with Pitavastatin or Simvastatin
- Limit Atorvastatin to 20 mg/day (and avoid Atorvastatin if Cyclosporine coadministered)
- Avoid Lovastatin if Cyclosporine coadministered
- Monitor for toxicity from Amiodarone, Sirolimus, Tacrolimus
- Modify Statins (increases Statin levels)
- Letermovir is a CYP2C8 Inhibitor
- Oral Hypoglycemic (Hypoglycemia risk)
- Increases Glyburide and Repaglinide levels (avoid if Cyclosporine coadministered)
- Increases Rosiglitazone levels
- Oral Hypoglycemic (Hypoglycemia risk)
- Letermovir may lower other drug levels
- Letermovir levels may be lowered by inducers of OATP1B1/3, P-gp or UGT1A1/3
IX. Resources
X. References
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- (2019) Med Lett Drugs Ther 61(1587): 199-201 [PubMed]