letermovir

General

Pronunciation:
le-term-oh-vir

Trade Name(s)

  • Prevymis

Ther. Class.
antivirals

Indications

Prevention of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT).

Action

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

Therapeutic Effect(s):

Preventing of clinically significant CMV infection following transplant.

Pharmacokinetics

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

Distribution: Widely distributed.

Protein Binding: 99%.

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

Half-life: 12 hr.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
IVrapidend of infusionunknown
POunknown0.75–2.25 hrunknown

Contraindication/Precautions

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: Lactation: Safety not established;
  • Pedi: Safety and effectiveness not established.

Adverse Reactions/Side Effects

CNS: headache

CV: peripheral edema, atrial fibrillation, tachycardia

GI: abdominal pain, diarrhea, nausea, vomiting

GU: ↑ serum creatinine

Hemat: anemia, neutropenia, thrombocytopenia

Resp: cough

Misc: fatigue

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • Letermovir is a substrate of organic anion-transporting polypeptide 1B1/3 (OATP1B1/3) transporters and a moderate inhibitor of CYP3A and an inhibitor of OATP1B1/3 transporters.
  • 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 ↑ 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; closely monitor phenytoin concentrations.
  • May ↑ glyburide, repaglinide, and pioglitazone; 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.
  • Rifampin may ↓ levels and ↑ risk of therapeutic failure; concurrent use not recommended.
  • May ↑ atorvastatin levels; do not exceed atorvastatin dose of 20 mg/day.
  • 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.

Route/Dosage

IV therapy should only be used when patients are unable to take oral therapy.

IV PO (Adults) 480 mg once daily started between Day 0 and Day 28 post-transplantation and continued through Day 100 post-transplantation. Concurrent use with cyclosporine–240 mg once daily started between Day 0 and Day 28 post-transplantation and continued through Day 100 post-transplantation.

Availability

Solution for injection (must be diluted): 20 mg/mL, 480 mg

Tablets: 240 mg, 480 mg

Assessment

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

Potential Diagnoses

Implementation

  • 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. Swallow tablets whole; do not crush, break or chew.

IV Administration

  • Intermittent Infusion: Diluent: 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 (EVA) or polyolefin (polypropylene and polyethylene), using infusion sets of PVC, polyethylene (PE), polybutadiene (PBD), silicone rubber (SR), styrene–butadiene copolymer (SBC), styrene-butadiene-styrene copolymer (SBS), or polystyrene (PS), with plasticizers of diethylhexyl phthalate (DEHP), tris (2-ethylhexyl) trimellitate (TOTM), benzyl butyl phthalate (BBP) 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 hrs at room temperature or 48 hrs 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
    • anti-thymocyte globulin
    • caspofungin
    • daptomycin
    • fentanyl
    • fluconazole
    • furosemide
    • insulin
    • magnesium sulfate
    • methotrexate
    • micafungin
  • Y-Site Compatibility
    • When diluted with D5W:
    • amphotericin B lipid complex
    • anidulafungin
    • cefazolin
    • ceftaroline
    • ceftriaxone
    • doripenem
    • famotidine
    • folic acid
    • ganciclovir
    • hydrocortisone sodium succinate
    • morphine
    • norepinephrine
    • pantoprazole
    • potassium chloride
    • potassium phosphate
    • tacrolimus
    • telavancin
    • tigecycline
  • Y-Site Incompatibility
    • amiodarone
    • amphotericin B liposomal
    • aztreonam
    • cefepime
    • ciprofloxacin
    • cyclosporine
    • diltiazem
    • filgrastim
    • gentamicin
    • levofloxacin
    • linezolid
    • lorazepam
    • midazolam
    • mycophenolate
    • ondansetron
    • palonosetron

Patient/Family Teaching

  • 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, herbal products.
  • Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

Prevention of CMV infection.

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