Letermovir

Non-Nucleoside, 3,4-dihydroquinazolinyl acetic acid
Competive inhibitor of pUL56 subunit of the viral terminase complex of Cytomegalovirus (CMV)
1. On binding pUL56, Letermovir blocks division of viral DNA in monomeric genome length DNA
2. Blocks DNA processing and packaging into procapsids, thereby preventing CMV replication

Give 480 mg IV over 1 hour or orally once daily
1. 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

Excreted in the feces
No dosage adjustment in Creatinine Clearance (CrCl) >10 ml/min
1. Unknown safety in CrCl <10 ml/min or Hemodialysis
No dosage adjustment in mild to moderate hepatic Impairment (Child-Pugh A or B)
1. Contraindicated in severe hepatic Impairment (Child-Pugh C)

Letermovir is a moderate CYP3A4 Inhibitor
1. Avoid with ergot alkaloids or Pimozide
Letermovir is a substrate of OATP1B1/3
1. Modify Statins (increases Statin levels)
  1. Avoid with Pitavastatin or Simvastatin
  2. Limit Atorvastatin to 20 mg/day (and avoid Atorvastatin if Cyclosporine coadministered)
  3. Avoid Lovastatin if Cyclosporine coadministered
  4. Monitor for toxicity from Amiodarone, Sirolimus, Tacrolimus
Letermovir is a CYP2C8 Inhibitor
1. Oral Hypoglycemic (Hypoglycemia risk)
  1. Increases Glyburide and Repaglinide levels (avoid if Cyclosporine coadministered)
  2. Increases Rosiglitazone levels
Letermovir may lower other drug levels
1. Warfarin
2. Voriconazole
Letermovir levels may be lowered by inducers of OATP1B1/3, P-gp or UGT1A1/3