le-TERM-oh-vir

Therapeutic Classification: antivirals

• Prevention of cytomegalovirus (CMV) infection and disease in CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant.
• Prevention of CMV disease in kidney transplant recipients at high risk (donor CMV seropositive/recipient CMV seronegative).

• Prevents viral DNA processing and packaging by inhibiting the CMV DNA terminase complex.

• Prevention of clinically significant CMV infection following transplant.

Absorption: 35% absorbed following oral administration (↑ when cyclosporine given); IV administration results in complete bioavailability.

Distribution: Widely distributed.

Protein Binding: 99%.

Metabolism/Excretion: Primarily metabolized in liver via UGT1A1/UGT1A3; 93% excreted in feces (70% as unchanged drug); <2% excreted in urine.

Half-life: 12 hr.

(plasma concentrations)

Contraindicated in:

• Concurrent use of pimozide or ergot alkaloids
• Concurrent use of pitavastatin and simvastatin when administered with cyclosporine
• Severe hepatic impairment.

Use Cautiously in:

• Renal impairment (CCr <50 mL/min; accumulation of IV vehicle may occur [closely monitor serum creatinine])
• OB: Safety not established in pregnancy
• Lactation: Safety not established in breastfeeding
• Pedi: Safety and effectiveness not established in children.

CV: peripheral edema, atrial fibrillation, tachycardia.

GI: abdominal pain, diarrhea, nausea, vomiting.

GU: ↑serum creatinine.

Hemat: anemia, neutropenia, thrombocytopenia.

Neuro: fatigue, headache.

Resp: cough.

Drug-Drug:

• May ↑ pimozide concentrations, which may ↑ risk of torsades de pointes; concurrent use contraindicated.
• May ↑ ergotamine and dihydroergotamine concentrations, which may ↑ risk of ergotism; concurrent use contraindicated.
• May significantly ↑ pitavastatin and simvastatin concentrations when concurrently administered with cyclosporine, which may ↑ risk of myopathy and rhabdomyolysis; concurrent use contraindicated.
• May ↑ amiodarone levels and risk of toxicity; closely monitor amiodarone concentrations.
• May ↓ warfarin levels and ↑ the risk for a thromboembolic event; closely monitor INR.
• May ↓ phenytoin levels; concurrent use not recommended.
• May ↑ glyburide, repaglinide, and pioglitazone levels; closely monitor blood glucose levels; when used concurrently with cyclosporine, avoid use with repaglinide.
• May ↓ voriconazole levels and ↑ risk of therapeutic failure; closely monitor for reduced effectiveness.
• Bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, nevirapine, phenobarbital, phenytoin, rifabutin, rifampin, and thioridazine may ↓ levels and ↑ risk of therapeutic failure; concurrent use not recommended.
• May ↑ atorvastatin levels; do not exceed atorvastatin dose of 20 mg/day; when used concurrently with cyclosporine, avoid use with atorvastatin.
• May ↑ pitavastatin and simvastatin levels; concurrent use not recommended.
• May ↑ fluvastatin, lovastatin, pravastatin, and rosuvastatin levels; consider ↓ dose of statin; when used concurrently with cyclosporine, avoid use with lovastatin.
• Concurrent use with cyclosporine↑ both cyclosporine and letermovir levels; ↓ dose of letermovir and closely monitor whole blood concentrations of cyclosporine.
• May ↑ sirolimus and tacrolimus levels; closely monitor whole blood concentrations of sirolimus and tacrolimus.
• May ↓ omeprazole and pantoprazole levels; closely monitor.

Drug-Natural Products:

• St. John's wort may ↓ levels and ↑ risk of therapeutic failure; concurrent use not recommended.

Hematopoietic Stem Cell Transplant

• IV, PO (Adults): 480 mg once daily started between Day 0 and Day 28 post-transplantation and continued through Day 100 post-transplantation. May be continued through Day 200 post-transplantation if the patient is at risk for late CMV infection and disease. Concurrent use with cyclosporine: 240 mg once daily started between Day 0 and Day 28 post-transplantation and continued through Day 100 post-transplantation. May be continued through Day 200 post-transplantation if the patient is at risk for late CMV infection and disease.

Kidney Transplant

• IV, PO (Adults): 480 mg once daily started between Day 0 and Day 7 post-transplantation and continued through Day 200 post-transplantation. Concurrent use with cyclosporine: 240 mg once daily started between Day 0 and Day 7 post-transplantation and continued through Day 200 post-transplantation.

• Tablets: 240 mg; 480 mg;
• Solution for injection: 20 mg/mL;

• Monitor for signs and symptoms of CMV reactivation (fatigue, fever, sore throat, muscle aches) when letermovir therapy completed.

• IV administration is only used when patient unable to take oral dose. IV and PO doses are interchangeable.
• PO: Administer once daily without regard to food. DNC: Swallow tablets whole; do not crush, break, or chew.

IV Administration:

• Intermittent Infusion: Add 1 vial to 250 mL 0.9% NaCl or D5W. Mix bag gently; do not shake.Mix only in compatible bags of polyvinyl chloride (PVC), ethylene vinyl acetate, or polyolefin (polypropylene and polyethylene), using infusion sets of PVC, polyethylene, polybutadiene, silicone rubber, styrene-butadiene copolymer, styrene-butadiene-styrene copolymer, or polystyrene, with plasticizers of diethylhexyl phthalate, tris (2-ethylhexyl) trimellitate, benzyl butyl phthalate, and catheters of radiopaque polyurethane. Undiluted solution is clear and colorless, and diluted solution is clear and colorless to yellow; do not administer solutions that are discolored or contain particulate matter. Solution is stable for 24 hr at room temperature or 48 hr if refrigerated, including storage of diluted solution through infusion duration.
• Rate: Administer via peripheral or central line over 1 hr; do not bolus.
• Y-Site Compatibility: When diluted with 0.9% NaCl:
  • ampicillin
  • ampicillin/sulbactam
  • antithymocyte globulin (equine)
  • caspofungin
  • daptomycin
  • fentanyl
  • fluconazole
  • furosemide
  • insulin, regular
  • magnesium sulfate
  • methotrexate
  • micafungin
• Y-Site Compatibility: When diluted with D5W:
  • amphotericin B lipid complex
  • anidulafungin
  • cefazolin
  • ceftaroline
  • ceftriaxone
  • famotidine
  • folic acid
  • ganciclovir
  • hydrocortisone sodium succinate
  • morphine
  • norepinephrine
  • pantoprazole
  • potassium chloride
  • potassium phosphates
  • tacrolimus
  • telavancin
  • tigecycline
• Y-Site Incompatibility:
  • amiodarone
  • amphotericin B liposomal
  • aztreonam
  • cefepime
  • ciprofloxacin
  • cyclosporine
  • diltiazem
  • filgrastim
  • gentamicin
  • levofloxacin
  • linezolid
  • lorazepam
  • midazolam
  • mycophenolate
  • ondansetron
  • palonosetron
.

• Instruct patient to take letermovir as directed for full course of therapy. Take missed doses as soon as remembered on day of dose; do not take more than 1/day. If remembered next day, skip previous dose and resume schedule; do not double doses.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

• Prevention of CMV infection.

Prevymis