Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Prevymis: 240 mg/12 mL (12 mL); 480 mg/24 mL (24 mL)
Tablet, Oral:
Prevymis: 240 mg, 480 mg
Pharmacology
Mechanism of Action
Letermovir inhibits cytomegalovirus (CMV) replication by targeting the CMV DNA terminase complex (pUL51, pUL56, pUL89), which is required for viral DNA processing and packaging. Letermovir affects production of genome unit lengths and alters virion maturation.
Pharmacokinetics/Pharmacodynamics
Distribution
IV: 45.5 L
Metabolism
Hepatic via UGT1A1/1A3 (minor)
Excretion
Feces: 93% (70% as unchanged drug); urine: <2%
Time to Peak
1.5 to 3 hours
Half-Life Elimination
12 hours
Protein Binding
99%
Use in Specific Populations
Special Populations: Renal Function Impairment
Letermovir AUC was approximately 1.9- and 1.4-fold higher in subjects with moderate (eGFR ≥30 to 59 mL/minute/1.73m2) and severe (eGFR <30 mL/minute/1.73m2) renal impairment, respectively (compared to healthy subjects [eGFR ≥90 mL/minute/1.73m2]; Kropeit 2017b).
Special Populations: Hepatic Function Impairment
Letermovir AUC was approximately 1.6- and 3.8-fold higher in female subjects with moderate (Child-Pugh class B) and severe (Child-Pugh class C) hepatic impairment, respectively, compared to healthy female subjects (Kropeit 2017a).
Use: Labeled Indications
Cytomegalovirus (prophylaxis): Prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT)
Contraindications
Concomitant administration with pimozide or ergot alkaloids; concomitant administration with pitavastatin and simvastatin when coadministered with cyclosporine.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to letermovir or any component of the formulation; concomitant administration with bosentan, lovastatin, and rosuvastatin when coadministered with cyclosporine.
Dosage and Administration
Dosing: Adult
Cytomegalovirus (CMV) prophylaxis, hematopoietic stem cell transplant (HSCT) patients: IV, Oral: 480 mg once daily beginning between day 0 and day 28 postallogeneic HSCT for CMV-seropositive recipients; continue through day 100 posttransplantation.
Dose adjustment for concomitant therapy with cyclosporine: Reduce letermovir to 240 mg once daily; if cyclosporine is discontinued (not held for supratherapeutic cyclosporine concentrations), increase letermovir to 480 mg once daily.
Dosing: Geriatric
Refer to adult dosing.
Reconstitution
Must be diluted prior to use. Add contents of vial to 250 mL of NS or D5W; mix bag gently and do not shake. Compatible IV bags include those made of polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), and polyolefin (polypropylene and polyethylene); not compatible with polyurethane-containing products.
Administration
Oral: Administer with or without food; swallow tablet whole.
IV: Administer as an IV infusion over 1 hour through a peripheral or central venous catheter; do not administer as IV bolus. Not compatible with polyurethane-containing IV administration sets; refer to manufacturer’s labeling for compatible infusion sets.
Storage
Injection: Store intact vials at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light; do not shake intact vials. Diluted solution is stable for ≤24 hours at room temperature or ≤48 hours at 2°C to 8°C (36°F to 46°F), including infusion time.
Tablets: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Drug Interactions
Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib. Monitor therapy
Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Consider therapy modification
AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine. Monitor therapy
Apixaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban. Monitor therapy
Aprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant. Avoid combination
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Asunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir. Avoid combination
Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination
AtorvaSTATin: Letermovir may increase the serum concentration of AtorvaSTATin. Management: Limit the atorvastatin dose to 20 mg daily when combined with letermovir. When letermovir is coadministered with cyclosporine, the use of atorvastatin (at any dose) is not recommended. Consider therapy modification
Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil adult dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects. Consider therapy modification
Avapritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avapritinib. Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose from 300 mg once daily to 100 mg once daily. Consider therapy modification
Axitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Axitinib. Monitor therapy
Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Monitor therapy
Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Monitor therapy
Bosentan: May decrease the serum concentration of Letermovir. Avoid combination
Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Avoid combination
Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Monitor therapy
Brigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Consider therapy modification
Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Consider therapy modification
Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic). Avoid combination
Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. Consider therapy modification
Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabidiol. Monitor therapy
Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy
Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving moderate inhibitors of CYP3A4. Consider therapy modification
Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid the concomitant use of cobimetinib and moderate CYP3A4 inhibitors. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose to 20 mg daily. Avoid combination
Codeine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Codeine. Monitor therapy
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. See full monograph for details. Use extra caution in patients with impaired renal and/or hepatic function. Consider therapy modification
CycloSPORINE (Systemic): Letermovir may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Letermovir. Management: Decrease the letermovir dose to 240 mg daily when combined with cyclosporine. Additionally, monitor for increased cyclosporine concentrations and toxicities when combined with letermovir. Consider therapy modification
CYP3A4 Substrates (High risk with Inhibitors): CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Exceptions: Alitretinoin (Systemic); Praziquantel; Trabectedin; Vinorelbine. Monitor therapy
Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Consider therapy modification
Deflazacort: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Consider therapy modification
Disopyramide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Disopyramide. Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dofetilide. Monitor therapy
Domperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Avoid combination
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Avoid combination
Eletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Management: The use of eletriptan within 72 hours of a moderate CYP3A4 inhibitor should be avoided. Consider therapy modification
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, two elexacaftor/tezacaftor/ivacaftor (100 mg/50 mg/75 mg) tablets should be given in the morning, every other day. Ivacaftor (150 mg) should be given in the morning, every other day on alternate days. Consider therapy modification
Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. Consider therapy modification
Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Monitor therapy
Encorafenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Encorafenib. Management: Avoid concomitant use of encorafenib and moderate CYP3A4 inhibitors whenever possible. If concomitant administration is unavoidable, decrease the encorafenib dose prior to initiation of the CYP3A4 inhibitor. See full monograph for details. Consider therapy modification
Entrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Entrectinib. Management: Avoid moderate CYP3A4 inhibitors during treatment with entrectinib. Reduce dose to 200 mg/day if combination cannot be avoided in adults and those 12 yrs of age or older with a BSA of at least 1.5 square meters. No alternative dosing provided for others. Consider therapy modification
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: When used concomitantly with moderate inhibitors of CYP3A4, eplerenone dosing recommendations vary by indication and international labeling. See full drug interaction monograph for details. Consider therapy modification
Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Ergot Derivatives: Letermovir may increase the serum concentration of Ergot Derivatives. Exceptions: Bromocriptine; Cabergoline; Nicergoline; Pergolide. Avoid combination
Estrogen Derivatives: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Estrogen Derivatives. Monitor therapy
Etravirine: May decrease the serum concentration of Letermovir. Avoid combination
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for most indications. See full monograph or prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary. Consider therapy modification
Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Avoid combination
Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant. Avoid combination
Gemfibrozil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. See separate drug interaction monographs for agents listed as exceptions. Monitor therapy
GlyBURIDE: Letermovir may increase the serum concentration of GlyBURIDE. Monitor therapy
Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Grazoprevir. Avoid combination
GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination. Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Management: Extreme caution, with possibly increased monitoring of ECGs, should be used if halofantrine is combined with moderate CYP3A4 inhibitors. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs. Monitor therapy
HMG-CoA Reductase Inhibitors (Statins): Letermovir may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Exceptions: AtorvaSTATin; Pitavastatin; Simvastatin. Monitor therapy
HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone. Monitor therapy
Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Consider therapy modification
Ifosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy
Imatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Imatinib. Monitor therapy
Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions may be required; consult full monograph content for age- and weight-specific dosage recommendations. Consider therapy modification
Ivosidenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivosidenib. Management: Avoid use of moderate CYP3A4 inhibitors with ivosidenib whenever possible. If combined, monitor for increased ivosidenib toxicities. Drugs listed as exceptions are discussed in further detail in separate drug interaction monographs. Consider therapy modification
Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination
Lefamulin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lefamulin. Management: Monitor for lefamulin adverse effects during coadministration of lefamulin tablets with moderate CYP3A4 inhibitors. Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lemborexant. Avoid combination
Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levamlodipine. Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Avoid combination
Lumacaftor and Ivacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor and Ivacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Lumateperone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lumateperone. Avoid combination
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: Lurasidone US labeling recommends reducing lurasidone dose by half with a moderate CYP3A4 inhibitor. Some non-US labeling recommends initiating lurasidone at 20 mg/day and limiting dose to 40 mg/day; avoid concurrent use of grapefruit products. Consider therapy modification
Manidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine. Monitor therapy
Meperidine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Meperidine. Monitor therapy
Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil. Monitor therapy
Modafinil: May decrease the serum concentration of Letermovir. Avoid combination
Nafcillin: May decrease the serum concentration of Letermovir. Avoid combination
Naldemedine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine. Monitor therapy
Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine. Monitor therapy
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Avoid combination
Neratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib. Avoid combination
Nevirapine: May diminish the therapeutic effect of Letermovir. Avoid combination
NiMODipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine. Monitor therapy
Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors in patients being treated with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 150 mg twice daily. Consider therapy modification
OxyCODONE: CYP3A4 Inhibitors (Moderate) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Monitor therapy
Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pexidartinib. Monitor therapy
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Letermovir. Avoid combination
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Monitor therapy
Pimozide: Letermovir may increase the serum concentration of Pimozide. Avoid combination
Pitavastatin: Letermovir may increase the serum concentration of Pitavastatin. Avoid combination
Propafenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine adult dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). Consider therapy modification
Repaglinide: Letermovir may increase the serum concentration of Repaglinide. Management: Monitor for increased repaglinide effects/toxicities (ie, hypoglycemia) if combined with letermovir. When letermovir is coadministered with cyclosporine, the use of repaglinide is not recommended. Monitor therapy
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Avoid combination
Rosiglitazone: Letermovir may increase the serum concentration of Rosiglitazone. Monitor therapy
Rupatadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine. Monitor therapy
Ruxolitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ruxolitinib. Monitor therapy
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Monitor therapy
SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin. Monitor therapy
Sildenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sildenafil. Monitor therapy
Silodosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin. Monitor therapy
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Avoid combination
Simvastatin: Letermovir may increase the serum concentration of Simvastatin. Avoid combination
Sirolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus. Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Consider therapy modification
Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Consider therapy modification
Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Consider therapy modification
Tacrolimus (Systemic): Letermovir may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy
Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Monitor therapy
Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tazemetostat. Management: Avoid coadministration of tazemetostat and moderate CYP3A4 inhibitors. If coadministration cannot be avoided, dose reductions are required. See full monograph for dosing recommendations. Consider therapy modification
Telithromycin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Telithromycin. Monitor therapy
Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Monitor therapy
Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, tezacaftor/ivacaftor should be given in the morning, every other day. Ivacaftor alone should be given in the morning, every other day on alternate days. Consider therapy modification
Thioridazine: May diminish the therapeutic effect of Letermovir. Avoid combination
Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Monitor therapy
Tofacitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tofacitinib. Monitor therapy
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Management: Jynarque dose requires adjustment when used with a moderate CYP3A4 inhibitor. See labeling or full interaction monograph for specific recommendations. Use of Samsca with moderate CYP3A4 ihibitors should generally be avoided. Consider therapy modification
Tolvaptan: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Consider therapy modification
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Monitor therapy
Triazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Consider therapy modification
Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Consider therapy modification
Udenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil. Monitor therapy
UGT1A1 Inducers: Letermovir may increase the serum concentration of UGT1A1 Inducers. Avoid combination
Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity. Avoid combination
Venetoclax: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Monitor therapy
Vindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine. Monitor therapy
Voriconazole: Letermovir may decrease the serum concentration of Voriconazole. Monitor therapy
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Avoid combination
Warfarin: Letermovir may decrease the serum concentration of Warfarin. Monitor therapy
Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg twice daily during coadministration with a moderate CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Consider therapy modification
Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Management: The starting adult dose of zopiclone should not exceed 3.75 mg if combined with a moderate CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. Consider therapy modification
Zuclopenthixol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Monitor therapy
Adverse Reactions
>10%:
Cardiovascular: Peripheral edema (14%)
Central nervous system: Headache (14%), fatigue (13%)
Gastrointestinal: Nausea (27%), diarrhea (26%), vomiting (19%), abdominal pain (12%)
Hematologic & oncologic: Decreased platelet count (grade 4: 27%)
Respiratory: Cough (14%)
1% to 10%:
Cardiovascular: Tachycardia (4%), atrial fibrillation (3%)
Hematologic & oncologic: Decreased hemoglobin (grade 4: 2%)
<1%, postmarketing, and/or case reports: Hypersensitivity reaction
Warnings/Precautions
Disease-related concerns:
- Hepatic impairment: Use is not recommended in patients with severe impairment (Child-Pugh class C).
- Renal impairment: Use with caution and closely monitor serum creatinine in patients with CrCl <50 mL/minute; accumulation of IV vehicle, hydroxypropyl betadex, may occur. Data are insufficient to make dosage recommendations in patients with CrCl ≤10 mL/minute or in patients on dialysis.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Dosage form specific issues:
- Injection: Contains hydroxypropyl betadex; use injection only in patients unable to take oral therapy.
Other warnings/precautions:
- Appropriate use: Not active against other herpes viruses besides cytomegalovirus (CMV) (Marschall 2012). Additional prophylaxis targeting herpes simplex virus (HSV) in HSV-positive hematopoietic stem cell transplant recipients receiving letermovir may be necessary (Tomblyn 2009).
- Resistance: Patients may have resistance to letermovir due to mutations in UL56. Cross resistance does not occur in populations with substitutions conferring resistance to CMV DNA polymerase inhibitors such as ganciclovir, cidofovir, and foscarnet.
Monitoring Parameters
Monitor for cytomegalovirus (CMV) reactivation; serum creatinine (especially in patients with CrCl <50 mL/minute [due to potential accumulation of IV vehicle hydroxypropyl betadex])
Pregnancy
Pregnancy Considerations
Adverse events were observed in some animal reproduction studies.
Patient Education
What is this drug used for?
- It is used to prevent cytomegalovirus (CMV) infection in people who have had a stem cell transplant.
Frequently reported side effects of this drug
- Diarrhea
- Nausea
- Cough
- Headache
- Loss of strength or energy
- Abdominal pain
- Vomiting
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Swelling of arms or legs
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
