Pronounciation

• (le-TERM-oh-vir)

Trade Name(s)

• Prevymis

• Antiviral

• pH 7.5

480 mg PO or IV once daily. Initiate between Day 0 and Day 28 posttransplantation (before or after engraftment) and continue through Day 100 posttransplantation. Reserve IV formulation for patients unable to take oral preparation. Transfer to oral dosing as soon as practical. IV and oral dose may be used interchangeably at the discretion of the physician. No dose adjustment necessary when switching formulations.

If cyclosporine is initiated after starting letermovir, decrease letermovir to 240 mg once daily beginning with the next scheduled dose.
■ If cyclosporine is discontinued after starting letermovir, increase letermovir to 480 mg once daily beginning with the next scheduled dose.
■ If cyclosporine dosing is interrupted due to high cyclosporine levels, no dose adjustment of letermovir is required.
■ No dose adjustment required based on renal impairment for patients with a creatinine clearance (CrCl) greater than 10 mL/min.
■ Data insufficient to make dosing recommendations in patients with CrCl 10 mL/min or less or in patients on dialysis.
■ No dose adjustment required for patients with mild or moderate hepatic impairment. Not recommended for patients with severe hepatic impairment.
■ No dose adjustment indicated based on age, body weight (up to 100 kg), gender, or race.

Available in single-dose vials containing 240 mg/12 mL or 480 mg/24 mL (both are 20 mg/mL). Do not shake the vial. Withdraw the desired dose and add to an IV bag containing 250 mL of NS or D5W; see Compatibility. Mix gently. Do not shake. May be colorless to slightly yellow.

Filters:

Specific information not available.

Storage:

Store single-dose vials at CRT in carton to protect from light. Diluted solutions are stable for up to 24 hours at RT or up to 48 hours under refrigeration (time includes time in storage through completion of the infusion).

Consider any item NOT listed as compatible to be INCOMPATIBLE.

Manufacturer states, “Should not be coadministered through the same IV line or cannula with other drug products and diluent combinations except those specifically listed.”

Compatible With:

IV Bags:

Polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), polyolefin (polypropylene and polyethylene).

Infusion Sets:

PVC, polyethylene (PE), polybutadiene (PBD), silicone rubber (SR), styrene-butadiene copolymer (SBC), styrene-butadiene-styrene copolymer (SBS), polystyrene (PS).

Plasticizers:

Diethylhexyl phthalate (DEHP), tris (2-ethylhexyl) trimellitate (TOTM), benzyl butyl phthalate (BBP).

Catheters:

Radiopaque polyurethane.

Y-site:

Diluted with NS:

Ampicillin, ampicillin/sulbactam, caspofungin, daptomycin, fentanyl citrate, fluconazole, furosemide, human insulin, magnesium sulfate, methotrexate, micafungin.

Diluted with D5W:

Amphotericin B, anidulafungin, cefazolin, ceftaroline, ceftriaxone, doripenem, famotidine, folic acid, ganciclovir, hydrocortisone sodium succinate, morphine, norepinephrine, pantoprazole, potassium chloride, potassium phosphate, tacrolimus, telavancin, tigecycline.

A single dose as an infusion at a constant rate over 1 hour. May be infused via a peripheral catheter or a central venous line.

Letermovir is an antiviral drug against cytomegalovirus (CMV). It inhibits the CMV DNA terminase complex, which is required for viral DNA processing and packaging. 99% bound to human plasma proteins in vitro. Metabolized in the liver via UGT1A1/1A3. Mean terminal half-life is 12 hours. Primarily eliminated in feces (93%) as unchanged drug (70%) with minimal excretion in urine.

Prophylaxis of CMV infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplantation (HSCT).

Patients receiving pimozide or ergot alkaloids.
■ Concomitant use with pitavastatin and simvastatin when coadministered with cyclosporine; see Drug/Lab Interactions.

Do not administer an IV bolus injection.
■ Concomitant use of letermovir and certain drugs may result in potentially significant drug interactions, which may lead to adverse reactions (letermovir or concomitant drug) or decreased therapeutic effect of letermovir or the concomitant drug; see Contraindications and Drug/Lab Interactions.

Monitor:

See Drug/Lab Interactions for specific monitoring requirements when letermovir is administered with other drugs.
■ See Contraindications.
■ After the completion of letermovir prophylaxis, monitoring for CMV reactivation is recommended.
■ Monitor SCr in patients with a CrCl less than 50 mL/min. Accumulation of the IV vehicle (hydroxypropyl betadex) can occur.

Patient Education:

Interacts with many drugs. Report the use of all prescription and nonprescription medications and herbal products to a healthcare provider.

Maternal/Child:

Data on safety for use in pregnancy not available; benefit must justify potential risks to fetus.
■ There are no data on the presence of letermovir in human milk, the effects on breast-fed infants, or the effects on milk production. Consider risk versus benefit.
■ Safety and effectiveness for use in pediatric patients not established.

Elderly:

Safety and effectiveness similar across older and younger subjects.

The following drug interactions apply only to coadministration of letermovir alone (without cyclosporine) unless otherwise noted. The magnitude of letermovir drug interactions on coadministered drugs may be different when letermovir is coadministered with cyclosporine; see cyclosporine monograph.

■ Letermovir is an inhibitor of OATP1B1/3 transporters; coadministration with drugs that are substrates of OATP1B1/3 transporters may result in clinically relevant increases in the plasma concentrations of the substrates.
■ If dose adjustments of concomitant medications are made due to treatment with letermovir, doses should be readjusted after treatment with letermovir is completed. Clinically significant interactions were not observed with acyclovir, digoxin, mycophenolate mofetil, fluconazole, posaconazole, ethinyl estradiol, and levonorgestrel.

Abdominal pain, cough, diarrhea, fatigue, headache, nausea, peripheral edema, and vomiting are most common. Cardiac events (atrial fibrillation, tachycardia) have been reported. Laboratory abnormalities include decreased ANC), hemoglobin, and platelets and increased serum creatinine. A hypersensitivity reaction with associated moderate dyspnea occurred in one subject after the first infusion of letermovir, leading to discontinuation. Nausea was the most common reason for drug discontinuation.

Notify physician of all side effects; most will be treated symptomatically. There is no specific antidote for overdose, and the effects of dialysis on removal of letermovir from the systemic circulation are unknown. Monitor drug/drug interactions closely for risk of increased side effects or reduced therapeutic effect. Should a hypersensitivity reaction occur, treat as necessary (e.g., antihistamines, epinephrine, corticosteroids). Resuscitate if indicated.