letermovir (Rx)

Brand and Other Names:Prevymis
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablet

  • 240mg
  • 480mg

solution for injection

  • 20mg/mL (vials contain 240mg/12mL or 480mg/24mL)
  • Further dilution required

Cytomegalovirus Infection Prophylaxis

Indicated for prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT)

480 mg PO/IV qDay; initiate between Day 0 and Day 28 posttransplantation (before or after engraftment) and continue through Day 100

Following the completion of prophylaxis, monitoring for CMV reactivation recommended

Use IV only in patients unable to take oral therapy; switch to oral administration as soon as feasible

Tablet and injection may be used interchangeably at the discretion of the physician; no dosage adjustment is necessary when switching formulations

Also see Administration

Dosage Modifications

Coadministration with cyclosporine

  • Decrease letermovir dose to 240 mg/day if coadministered with cyclosporine (monitor cyclosporine levels)
  • If cyclosporine initiated after letermovir, decrease the next letermovir dose to 240 mg/day
  • If cyclosporine discontinued after starting letermovir, increase the next letermovir dose to 480 mg/day
  • If cyclosporine dosing is interrupted because of high cyclosporine levels, no dose adjustment of letermovir is needed

Renal impairment

  • CrCl >10 mL/min: No dosage adjustment required
  • CrCl ≤10 mL/min or patient on dialysis: Data are insufficient to make dosing recommendations
  • Hydroxypropyl betadex (IV vehicle) may accumulate if CrCl <50 mL/min; closely monitor serum creatinine levels in patients receiving IV letermovir

Hepatic impairment

  • Mild or moderate (Child-Pugh A or B): No dosage adjustment required
  • Severe (Child-Pugh C): Not recommended

<18 years: Safety and efficacy not established

No dosage adjustment is required based on age

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Interactions

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            Contraindicated (8)

            • dihydroergotamine

              letermovir increases levels of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of letermovir and ergot alkaloids is contraindicated due to risk of ergotism.

            • dihydroergotamine inhaled

              letermovir increases levels of dihydroergotamine inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of letermovir and ergot alkaloids is contraindicated due to risk of ergotism.

            • dihydroergotamine intranasal

              letermovir increases levels of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of letermovir and ergot alkaloids is contraindicated due to risk of ergotism.

            • ergotamine

              letermovir increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of letermovir and ergot alkaloids is contraindicated due to risk of ergotism.

            • lonafarnib

              letermovir will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.

            • pimozide

              letermovir increases levels of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of letermovir and pimozide is contraindicated due to risk of QT prolongations and torsades de pointes.

            • pitavastatin

              letermovir increases levels of pitavastatin by Other (see comment). Contraindicated. Comment: Coadministration of letermovir and pitavastatin is not recommended. When letermovir is coadministered with cyclosporine, use of either pitavastatin is contraindicated due to significantly increased pitavastatin concentrations and risk of myopathy or rhabdomyolysis. .

            • simvastatin

              letermovir increases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of letermovir and simvastatin is not recommended. When letermovir is coadministered with cyclosporine, use of either simvastatin is contraindicated due to significantly increased pitavastatin or simvastatin concentrations and risk of myopathy or rhabdomyolysis. .

            Serious - Use Alternative (32)

            • apalutamide

              apalutamide will decrease the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.

              apalutamide will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • avapritinib

              letermovir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

            • carbamazepine

              carbamazepine will decrease the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.

              carbamazepine will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • efavirenz

              efavirenz will decrease the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.

            • encorafenib

              letermovir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • entrectinib

              letermovir will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • infigratinib

              letermovir will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lasmiditan

              lasmiditan increases levels of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • lemborexant

              letermovir will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.

            • lurbinectedin

              letermovir will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • midazolam intranasal

              letermovir will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of moderate CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.

            • mobocertinib

              letermovir will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use of moderate CYP3A4 inhibitor unavoidable, reduce mobocertinib dose by ~50% (eg, 160 to 80 mg); closely monitor QTc interval.

            • nefazodone

              nefazodone will increase the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.

            • pemigatinib

              letermovir will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

            • pexidartinib

              letermovir will increase the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pexidartinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.

            • phenobarbital

              phenobarbital will decrease the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.

              phenobarbital will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • phenytoin

              phenytoin will decrease the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.

              phenytoin will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • primidone

              primidone will increase the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.

              primidone will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • repaglinide

              letermovir, repaglinide. Either increases levels of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations. When letermovir is coadministered with cyclosporine, avoid use with repaglinide.

            • rifampin

              rifampin will decrease the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.

              rifampin will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • selumetinib

              letermovir will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

            • siponimod

              letermovir will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • sotorasib

              sotorasib will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

            • St John's Wort

              St John's Wort will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • tazemetostat

              letermovir will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with moderate CYP3A4 inhibitors. If coadministration is unavoidable, reduce tazemetostat current dose (see drug monograph Dosage Modifications).

            • tenofovir AF

              tenofovir AF will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • tenofovir DF

              tenofovir DF will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • tepotinib

              tepotinib will increase the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

            • tipranavir

              tipranavir will increase the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.

              tipranavir will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • vinblastine

              vinblastine will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            Monitor Closely (203)

            • abiraterone

              letermovir increases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • acarbose

              letermovir will increase the level or effect of acarbose by unspecified interaction mechanism. Use Caution/Monitor. Monitor glucose concentrations

            • alfentanil

              letermovir increases levels of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • alfuzosin

              letermovir increases levels of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • aliskiren

              letermovir increases levels of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • almotriptan

              letermovir increases levels of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • alprazolam

              letermovir increases levels of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ambrisentan

              letermovir increases levels of ambrisentan by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • amiodarone

              letermovir increases levels of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Close monitoring for increased amiodarone effects and concentrations is recommended when concomitantly used with letermovir.

            • amitriptyline

              letermovir increases levels of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • amlodipine

              letermovir increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • apalutamide

              apalutamide will decrease the level or effect of letermovir by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces OATP1B1 and may decrease systemic exposure of drugs that are OATP1B1 substrates.

            • aprepitant

              letermovir increases levels of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • aripiprazole

              letermovir increases levels of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atazanavir

              letermovir increases levels of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atogepant

              letermovir will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atorvastatin

              atorvastatin increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with atorvastatin and letermovir, do not exceed an atorvastatin dosage of 20 mg daily. Closely monitor patients for myopathy and rhabdomyolysis. When letermovir is coadministered with cyclosporine, use of atorvastatin is not recommended. .

            • berotralstat

              berotralstat will increase the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • bexarotene

              letermovir increases levels of bexarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • bosentan

              letermovir increases levels of bosentan by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • bromocriptine

              letermovir increases levels of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • budesonide

              letermovir increases levels of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • buprenorphine

              letermovir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • buspirone

              letermovir increases levels of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • caffeine

              letermovir increases levels of caffeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • canagliflozin

              letermovir will increase the level or effect of canagliflozin by unspecified interaction mechanism. Use Caution/Monitor. Monitor glucose concentrations.

            • cannabidiol

              letermovir will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • carbamazepine

              carbamazepine increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • caspofungin

              caspofungin increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of caspofungin by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • cevimeline

              letermovir increases levels of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chlordiazepoxide

              letermovir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chlorpheniramine

              letermovir increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cilostazol

              letermovir increases levels of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cinacalcet

              letermovir increases levels of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • citalopram

              letermovir increases levels of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clarithromycin

              clarithromycin increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • clindamycin

              letermovir increases levels of clindamycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clomipramine

              letermovir increases levels of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clonazepam

              letermovir increases levels of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clopidogrel

              letermovir increases levels of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clorazepate

              letermovir increases levels of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clotrimazole

              clotrimazole increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • clozapine

              letermovir increases levels of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cobicistat

              cobicistat increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • cocaine

              letermovir increases levels of cocaine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • codeine

              letermovir increases levels of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • colchicine

              letermovir increases levels of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cyclophosphamide

              letermovir increases levels of cyclophosphamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cyclosporine

              letermovir, cyclosporine. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decrease letermovir dosage to 240 mg/day. Frequently monitor cyclosporine concentrations during treatment and after discontinuation of letermovir and adjust cyclosporine dose accordingly.

            • dapagliflozin

              letermovir will increase the level or effect of dapagliflozin by unspecified interaction mechanism. Use Caution/Monitor. Monitor glucose concentrations.

            • dapsone

              letermovir increases levels of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • darifenacin

              letermovir increases levels of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • darunavir

              letermovir increases levels of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • desogestrel

              letermovir increases levels of desogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dexamethasone

              letermovir increases levels of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dextromethorphan

              letermovir increases levels of dextromethorphan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dextromethorphan/menthol

              letermovir increases levels of dextromethorphan/menthol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diazepam intranasal

              letermovir will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

            • diltiazem

              diltiazem will increase the level or effect of letermovir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • disopyramide

              letermovir increases levels of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • docetaxel

              letermovir increases levels of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dofetilide

              letermovir increases levels of dofetilide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dolasetron

              letermovir increases levels of dolasetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • donepezil

              letermovir increases levels of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • doxorubicin

              letermovir increases levels of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dronabinol

              letermovir increases levels of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dutasteride

              letermovir increases levels of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • efavirenz

              letermovir increases levels of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elbasvir/grazoprevir

              letermovir increases levels of elbasvir/grazoprevir by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • eltrombopag

              eltrombopag increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • eluxadoline

              letermovir increases levels of eluxadoline by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • empagliflozin

              letermovir will increase the level or effect of empagliflozin by unspecified interaction mechanism. Use Caution/Monitor. Monitor glucose concentrations.

            • enalapril

              letermovir increases levels of enalapril by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • eplerenone

              letermovir increases levels of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erlotinib

              letermovir increases levels of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin base

              erythromycin base increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of erythromycin base by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

              letermovir increases levels of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin ethylsuccinate

              letermovir increases levels of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin lactobionate

              letermovir increases levels of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • esomeprazole

              letermovir increases levels of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estradiol

              letermovir increases levels of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • eszopiclone

              letermovir increases levels of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ethosuximide

              letermovir increases levels of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • etonogestrel

              letermovir increases levels of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • etoposide

              letermovir increases levels of etoposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • everolimus

              letermovir increases levels of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • exemestane

              letermovir increases levels of exemestane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ezetimibe

              letermovir increases levels of ezetimibe by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • felodipine

              letermovir increases levels of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fentanyl

              letermovir increases levels of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fexofenadine

              letermovir increases levels of fexofenadine by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

              letermovir increases levels of fexofenadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • finasteride

              letermovir increases levels of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • finerenone

              letermovir will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • flurazepam

              letermovir increases levels of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • flutamide

              letermovir increases levels of flutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluticasone furoate

              letermovir increases levels of fluticasone furoate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluticasone inhaled

              letermovir increases levels of fluticasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluticasone intranasal

              letermovir increases levels of fluticasone intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluvastatin

              letermovir increases levels of fluvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of letermovir with fluvastatin, a dosage reduction may be necessary. Closely monitor patients for myopathy and rhabdomyolysis. When letermovir is coadministered with cyclosporine, use of fluvastatin is not recommended. .

            • fostemsavir

              fostemsavir will increase the level or effect of letermovir by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 transporter. If possible, avoid coadministration or modify dose of OATP1B1/3 substrates coadministered with fostemsavir.

            • galantamine

              letermovir increases levels of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • gemfibrozil

              gemfibrozil increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • glecaprevir/pibrentasvir

              glecaprevir/pibrentasvir increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of glecaprevir/pibrentasvir by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • glyburide

              letermovir, glyburide. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Monitor glucose concentrations.

            • haloperidol

              letermovir increases levels of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • hydrocodone

              letermovir increases levels of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression.

            • hydrocortisone

              letermovir increases levels of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ibrutinib

              letermovir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

            • ifosfamide

              letermovir decreases effects of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of a CYP3A4 inhibitor may decrease metabolism of ifosfamide, potentially reducing ifosfamide therapeutic effects.

            • iloperidone

              letermovir increases levels of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • imatinib

              letermovir increases levels of imatinib by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

              letermovir increases levels of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • imipramine

              letermovir increases levels of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • indinavir

              indinavir increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • irinotecan

              letermovir increases levels of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isradipine

              letermovir increases levels of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ivacaftor

              letermovir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • ivosidenib

              letermovir will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with moderate CYP3A4 inhibitors may increase ivosidenib plasma concentrations, thus increasing the risk of QTc prolongation. Monitor for increased risk of QTc interval prolongation.

            • ketoconazole

              ketoconazole increases effects of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lansoprazole

              letermovir increases levels of lansoprazole by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.

            • lefamulin

              letermovir will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for adverse effects if lefamulin is coadministered with moderate CYP3A inhibitors.

            • lenvatinib

              lenvatinib increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • letrozole

              letermovir increases levels of letrozole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levamlodipine

              letermovir will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

            • levothyroxine

              letermovir increases levels of levothyroxine by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • lidocaine

              letermovir increases levels of lidocaine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lopinavir

              letermovir increases levels of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • loratadine

              letermovir increases levels of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lovastatin

              lovastatin increases levels of letermovir by increasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of letermovir with lovastatin may require a dosage reduction. Closely monitor patients for myopathy and rhabdomyolysis. When letermovir is coadministered with cyclosporine, use of lovastatin is not recommended.

            • methadone

              letermovir increases levels of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • methotrexate

              letermovir increases levels of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • metyrapone

              metyrapone increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • midazolam

              letermovir increases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mifepristone

              mifepristone increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases effects of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • miglitol

              letermovir will increase the level or effect of miglitol by unspecified interaction mechanism. Use Caution/Monitor. Monitor glucose concentrations

            • mirtazapine

              letermovir increases levels of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • modafinil

              letermovir increases levels of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mometasone inhaled

              letermovir increases levels of mometasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • montelukast

              letermovir increases levels of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nateglinide

              letermovir will increase the level or effect of nateglinide by unspecified interaction mechanism. Use Caution/Monitor. Monitor glucose concentrations

              letermovir increases levels of nateglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nelfinavir

              nelfinavir increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nevirapine

              letermovir increases levels of nevirapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nicardipine

              letermovir increases levels of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nifedipine

              letermovir increases levels of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nisoldipine

              letermovir increases levels of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nitrendipine

              letermovir increases levels of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • norethindrone

              letermovir increases levels of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oliceridine

              letermovir will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

            • olmesartan

              letermovir increases levels of olmesartan by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • omeprazole

              letermovir increases levels of omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor and dose adjustment may be necessary.

            • ondansetron

              letermovir increases levels of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxybutynin

              letermovir increases levels of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxycodone

              letermovir increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • paclitaxel

              paclitaxel increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of paclitaxel by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

              letermovir increases levels of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pantoprazole

              letermovir increases levels of pantoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor and dose adjustment may be necessary.

            • pazopanib

              pazopanib increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • phenytoin

              letermovir will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Monitor phenytoin levels.

            • pioglitazone

              letermovir, pioglitazone. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations. Monitor glucose levels.

            • pravastatin

              letermovir increases levels of pravastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of letermovir with pravastatin may require a dosage reduction. Closely monitor patients for myopathy and rhabdomyolysis. When letermovir is coadministered with cyclosporine, the dose of pravastatin should not exceed 20 mg PO qDay.

            • progesterone micronized

              letermovir increases levels of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • progesterone, natural

              letermovir increases levels of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • propafenone

              letermovir increases levels of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • propranolol

              letermovir increases effects of propranolol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • quetiapine

              letermovir increases levels of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • quinidine

              letermovir increases levels of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • quinine

              letermovir increases levels of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rabeprazole

              letermovir increases levels of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ramelteon

              letermovir increases levels of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ranolazine

              letermovir increases levels of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ribociclib

              letermovir will increase the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifaximin

              letermovir increases levels of rifaximin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rimegepant

              letermovir will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid repeating rimegepant dose within 48 hr if coadministered with a moderate CYP3A4 inhibitor.

            • risperidone

              letermovir increases levels of risperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ritonavir

              ritonavir increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rivaroxaban

              letermovir increases levels of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rosiglitazone

              letermovir will increase the level or effect of rosiglitazone by unspecified interaction mechanism. Use Caution/Monitor. Monitor glucose concentrations.

            • rosuvastatin

              letermovir increases levels of rosuvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of letermovir with fluvastatin may require a dosage reduction. Closely monitor patients for myopathy and rhabdomyolysis. When letermovir is coadministered with cyclosporine, the dose of rosuvastatin should not exceed 5 mg PO qDay . .

            • salmeterol

              letermovir increases levels of salmeterol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • saquinavir

              saquinavir increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • saxagliptin

              letermovir increases levels of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sertraline

              letermovir increases levels of sertraline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sildenafil

              letermovir increases levels of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sirolimus

              letermovir increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor sirolimus plasma concentrations during treatment and after discontinuation of letemovir and adjust dose of sirolimus accordingly. When letermovir is coadministered with cyclosporine, sirolimus is recommended to be taken 4 hr after cyclosporine oral (MODIFIED) administration. Higher doses of sirolimus are needed to maintain the recommended sirolimus trough concentration ranges if cyclosporine is discontinued from combination therapy.

            • solifenacin

              letermovir increases levels of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sorafenib

              letermovir increases levels of sorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sufentanil

              letermovir increases levels of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sufentanil SL

              letermovir will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of sufentanil SL with any CYP3A4 inhibitor may increase sufentanil plasma concentration, and, thereby increase or prolonged adverse effects, including potentially fatal respiratory depression.

            • sunitinib

              letermovir increases levels of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tacrolimus

              tacrolimus increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor tacrolimus plasma concentrations during treatment and after discontinuation of letemovir and adjust dose of tacrolimus accordingly.

            • tadalafil

              letermovir increases levels of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tamoxifen

              letermovir increases levels of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • telmisartan

              telmisartan increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of telmisartan by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • teriflunomide

              teriflunomide increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • tucatinib

              tucatinib will increase the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

            • valsartan

              valsartan increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of valsartan by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • voclosporin

              letermovir will increase the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce voclosporin daily dosage to 15.8 mg PO in AM and 7.9 mg PO in PM.

              voclosporin, letermovir. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

            • voriconazole

              letermovir will decrease the level or effect of voriconazole by unspecified interaction mechanism. Use Caution/Monitor. Closely monitor for reduced effectiveness of voriconazole.

            • voxilaprevir

              voxilaprevir increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • warfarin

              letermovir will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Monitor INR.

            • zaleplon

              letermovir increases levels of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • zanubrutinib

              letermovir will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib dose when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib. See zanubrutinib Dosage Modifications for precise recommendation.

            • zileuton

              letermovir increases levels of zileuton by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ziprasidone

              letermovir increases levels of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • zolpidem

              letermovir increases levels of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            Minor (2)

            • entecavir

              letermovir, entecavir. Either increases levels of the other by decreasing renal clearance. Minor/Significance Unknown. Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug.

            • voclosporin

              voclosporin will increase the level or effect of letermovir by Other (see comment). Minor/Significance Unknown. Information suggests voclosporin (an OATP1B1 inhibitor) may increase in the concentration of OATP1B1 substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when coadministered with voclosporin.

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            Adverse Effects

            >10%

            Nausea (27%)

            Diarrhea (26%)

            Vomiting (19%)

            Peripheral edema (14%)

            Cough (14%)

            Headache (14%)

            Fatigue (13%)

            Abdominal pain (12%)

            Laboratory abnormalities with incidence greater than placebo

            • Platelets <25,000 cells/mcL 27% (placebo 21%)

            1-10%

            Tachycardia (4%)

            Atrial fibrillation (3%)

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            Warnings

            Contraindications

            Pimozide, ergot alkaloids (see Cautions)

            Pitavastatin or simvastatin when coadministered with cyclosporine (see Cautions)

            Cautions

            Coadministration of letermovir with certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions or reduced therapeutic effect of either drug (see Contraindications)

            Drug interaction overview

            • Cyclosporine and letermovir may increase plasma concentrations of each other (see Dosage Modifications)
            • Contraindicated drug interactions
              • Pimozide: Coadministration with pimozide may result in increased concentrations of pimozide, owing to inhibition of CYP3A4 by letermovir, which may lead to QT prolongation and torsades de pointes
              • Ergot alkaloids: Coadministration with ergot alkaloids may result in increased concentrations of ergot alkaloids (ergotamine and dihydroergotamine), owing to inhibition of CYP3A by letermovir, which may lead to ergotism
              • Pitavastatin or simvastatin when coadministered with cyclosporine: Coadministration of letermovir in combination with cyclosporine may result in significantly increased pitavastatin or simvastatin concentrations, which may lead to myopathy or rhabdomyolysis
            • Potential for other drugs to affect letermovir
              • Letermovir is a substrate of CYP3A (minor), CYP2D6 (minor), UGT1A1, and UGT1A3, and transporters OATP1B1/3 and P-gp; oxidative metabolism is considered to be a minor elimination pathway based on in vivo human data
              • Coadministration of letermovir with inducers of P-gp and/or UGT 1A1/3 is not recommended owing to potential for decreased letermovir plasma concentrations
              • Inhibitors of OATP1B1/3 may result in increases in letermovir plasma concentrations
              • Changes in letermovir plasma concentrations due to inhibition of P-gp or UGTs are not anticipated to be clinically relevant
            • Potential for letermovir to affect other drugs
              • Letermovir is a time-dependent inhibitor and inducer of CYP3A in vitro; drug interaction studies showed a net effect of letermovir on CYP3A is moderate inhibition
              • Letermovir is a reversible inhibitor of CYP2C8 in vitro; if coadministered, plasma concentrations of CYP2C8 substrates are predicted to increase
              • Letermovir induces CYP2C9 and CYP2C19; if coadministered, plasma concentrations of CYP2C9 and CYP2C19 substrates may decrease
              • Letermovir induces CYP2B6 in vitro; clinical relevance unknown
              • Letermovir inhibits efflux transporters P-gp, breast cancer resistance protein (BCRP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), OAT3, and hepatic uptake transporter OATP1B1/3 in vitro; coadministration with substrates of OATP1B1/3 transporters (eg, atorvastatin, a known substrate of CYP3A, OATP1B1/3, and potentially BCRP) may result in a clinically relevant increase in plasma concentrations of OATP1B1/3 substrates
              • Note: There were no clinically relevant changes in plasma concentrations of digoxin, a P-gp substrate, or acyclovir, an OAT3 substrate
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            Pregnancy & Lactation

            Pregnancy

            No data are available regarding use in pregnant women

            In animal reproduction studies, embryo-fetal developmental toxicity (including fetal malformations) was observed in rats during the period of organogenesis at letermovir exposures (AUC) 11 times higher than human exposure at the recommended human dose (RHD); in rabbits, no embryo-fetal developmental toxicity was noted at exposures that were not maternally toxic (up to letermovir exposures 2 times higher than human exposure at the RHD)

            Infertility: No data are available on the effect of letermovir on human fertility; decreased fertility due to testicular toxicity observed in male rats

            Lactation

            Unknown if present in human breast milk, affects human milk production, or has effects on the breastfed child

            When administered to lactating rats, letermovir was present in the milk of lactating rats as well as the blood of nursing pups

            The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Antiviral drug against CMV; inhibits the CMV DNA terminase complex (pUL51, pUL56, and pUL89), which is required for viral DNA processing and packaging by affecting the production of proper unit length genomes and interfering with virion maturation

            Absorption

            Peak plasma time, PO: 0.75-2.25 hr

            Peak plasma concentration, 480 mg/day PO: 13,000 ng/mL

            Time to steady-state: 9-10 days

            Bioavailability

            • Healthy subjects, no cyclosporine: 94%
            • HSCT recipients, no cyclosporine: 35% (480 mg/day)
            • HSCT recipients, with cyclosporine: 85% (240 mg/day)

            AUC

            • Accumulation ratio: 1.22
            • HSCT recipients
              • 480 mg/day PO, no cyclosporine: 34,400 ng·hr/mL
              • 480 mg/day IV, no cyclosporine: 100,000 ng·hr/mL
              • 240 mg/day PO, with cyclosporine: 60,800 ng·hr/mL
              • 240 mg/day IV, with cyclosporine: 70,300 ng·hr/mL
            • Healthy subjects
              • 480 mg PO/day: 71,500 ng·hr/mL

            Distribution

            Vd, HSCT recipients (IV): 45.5 L

            Protein bound: 99% across concentration range of 0.2-50 mg/L

            Blood-to-plasma ratio: 0.56 across concentration range of 0.1-10 mg/L

            Metabolism

            UGT1A1/1A3

            CYP3A, CYP2D6 (minor)

            Elimination

            Route: Hepatic uptake (OATP1B1/3)

            Half-life: 12 hr (480 mg/day IV)

            Excretion: 93% feces (70% unchanged); <2% urine

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            Administration

            Oral Administration

            May take with or without food

            Swallow tablets whole; do not crush or chew

            IV Compatibilities

            0.9% NaCl

            D5W

            Compatible drugs when letermovir prepared with 0.9% NaCl

            • Ampicillin sodium, ampicillin sodium/sulbactam sodium, antithymocyte globulin, caspofungin, daptomycin, fentanyl citrate, fluconazole, furosemide, human insulin, magnesium sulfate, methotrexate, micafungin

            Compatible drugs when letermovir prepared with D5W

            • Amphotericin B (lipid complex)*, anidulafungin, cefazolin sodium, ceftaroline, ceftriaxone sodium, doripenem, famotidine, folic acid, ganciclovir sodium, hydrocortisone sodium succinate, morphine sulfate, norepinephrine bitartrate, pantoprazole sodium, potassium chloride, potassium phosphate, tacrolimus, telavancin, tigecycline
            • *Amphotericin B (lipid complex; Abelcet) is compatible with letermovir; however, amphotericin B (liposomal; AmBisome) is incompatible

            Compatible IV bags

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

            Compatible infusion sets

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

            Compatible plasticizers

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

            Compatible catheters

            • Radiopaque polyurethane

            IV Incompatibilities

            Amiodarone, amphotericin B (liposomal), aztreonam, cefepime hydrochloride, ciprofloxacin, cyclosporine, diltiazem hydrochloride, filgrastim, gentamicin sulfate, levofloxacin, linezolid, lorazepam, midazolam HCl, mycophenolate mofetil hydrochloride, ondansetron, palonosetron

            IV Preparation

            Vials are for single use only; discard any unused portion

            Letermovir solution must be further diluted before IV administration

            Inspect vial contents for discoloration and particulate matter before dilution; should appear as a clear, colorless solution

            Do not use the vial if the solution is discolored or contains visible particles

            Do not shake vial

            Add one single-dose vial into a 250-mL prefilled IV bag containing either 0.9% NaCl or D5W; mix bag gently, do not shake

            Use compatible IV bags and infusion set materials (see IV Compatibilities); note that letermovir is not recommended for use with polyurethane-containing IV administration set tubing

            Once diluted, the solution is clear and ranges from colorless to yellow; variations of color within this range do not affect the quality of the product

            Inspect visually for particulate matter and discoloration before administration, whenever solution and container permit

            Discard if discoloration or visible particles are observed

            IV Administration

            Administer the entire contents of the IV bag by IV infusion via a peripheral catheter or central venous line at a constant rate over 1 hr

            Do not administer as IV bolus

            Storage

            Tablets

            • Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)
            • Store in original package until use

            Solution for injection

            • Unopened vials
              • Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)
              • Store in the original carton to protect from light
            • Diluted IV solution
              • Room temperature (20-25°C [68-77°F]): Stable for up to 24 hr
              • Refrigerated (2-8°C [36-46°F]): Stable for up to 48 hr
              • Note: These times includes storage of the diluted solution in the IV bag through the duration of infusion
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            Patient Handout

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.