letermovir

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.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	unknown
PO	unknown	0.75–2.25 hr	unknown

Contraind./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: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema, atrial fibrillation, tachycardia

GI: abdominal pain, diarrhea, nausea, vomiting

GU: ↑serum creatinine

Hemat: anemia, neutropenia, thrombocytopenia

Neuro: fatigue, headache

Resp: cough

Interactions ⬆ ⬇

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 pioglitazonelevels; 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.

Route/Dosage ⬆ ⬇

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

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.

Availability ⬆ ⬇

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

Assessment ⬆ ⬇

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

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. DNC: 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, 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.

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, or herbal products.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇