Letermovir (Prevymis) Dose in Adults:

Risk Factor C (Monitor therapy)

Abemaciclib

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib.

AmLODIPine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine.

Apixaban

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban.

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.

Benzhydrocodone

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased.

Blonanserin

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin.

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.

Cannabidiol

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabidiol.

Cannabis

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased.

Codeine

CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Codeine.

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.

Disopyramide

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Disopyramide.

Dofetilide

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dofetilide.

Dronabinol

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol.

Eltrombopag

May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates.

Erdafitinib

May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.

Estrogen Derivatives

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Estrogen Derivatives.

Gemfibrozil

May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. See separate drug interaction monographs for agents listed as exceptions.

GlyBURIDE

Letermovir may increase the serum concentration of GlyBURIDE.

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.

HMG-CoA Reductase Inhibitors (Statins)

Letermovir may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Exceptions: AtorvaSTATin; Pitavastatin; Simvastatin.

HYDROcodone

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone.

Ifosfamide

CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide.

Imatinib

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Imatinib.

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.

Levamlodipine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levamlodipine.

Lumacaftor

May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates.

Manidipine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine.

Meperidine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Meperidine.

Mirodenafil

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil.

Naldemedine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine.

Nalfurafine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine.

NiMODipine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine.

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.

Pexidartinib

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pexidartinib.

P-glycoprotein/ABCB1 Inhibitors

May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).

Pimecrolimus

CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus.

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.

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.

Rosiglitazone

Letermovir may increase the serum concentration of Rosiglitazone.

Rupatadine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine.

Ruxolitinib

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ruxolitinib.

Salmeterol

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol.

SAXagliptin

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin.

Sildenafil

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sildenafil.

Silodosin

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin.

Tacrolimus (Systemic)

Letermovir may increase the serum concentration of Tacrolimus (Systemic).

Tamsulosin

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin.

Telithromycin

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Telithromycin.

Teriflunomide

May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates.

Tetrahydrocannabinol

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol.

Ticagrelor

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor.

Tofacitinib

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tofacitinib.

Trabectedin

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin.

Udenafil

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil.

Vilazodone

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone.

Vindesine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine.

Voriconazole

Letermovir may decrease the serum concentration of Voriconazole.

Warfarin

Letermovir may decrease the serum concentration of Warfarin.

Zuclopenthixol

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol.

Risk Factor D (Consider therapy modification)

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

GuanFACINE

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination.

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.

Ivacaftor

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions may be required; consult full monograph content for product-specific recommendations. No dose adjustment is needed when using ivacaftor/lumacaftor with a moderate CYP3A4 inhibitor.

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.

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.

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.

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.).

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.

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).

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.

Tezacaftor

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor. Management: When combined with moderate CYP3A4 inhibitors, tezacaftor/ivacaftor or elexacaftor/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.

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.

Tolvaptan

May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates.

Triazolam

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors.

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.

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.

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.

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.

Risk Factor X (Avoid combination)

Aprepitant

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant.

Asunaprevir

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir.

Asunaprevir

OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir.

Bosentan

May decrease the serum concentration of Letermovir.

Bosutinib

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib.

Budesonide (Systemic)

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic).

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.

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.

Elagolix

OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix.

Ergot Derivatives

Letermovir may increase the serum concentration of Ergot Derivatives. Exceptions: Bromocriptine; Cabergoline; Nicergoline; Pergolide.

Etravirine

May decrease the serum concentration of Letermovir.

Flibanserin

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin.

Fosaprepitant

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant.

Grazoprevir

OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Grazoprevir.

Ivabradine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine.

Lasmiditan

May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.

Lemborexant

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lemborexant.

Lomitapide

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide.

Lumateperone

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lumateperone.

Modafinil

May decrease the serum concentration of Letermovir.

Nafcillin

May decrease the serum concentration of Letermovir.

Naloxegol

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol.

Neratinib

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib.

Nevirapine

May diminish the therapeutic effect of Letermovir.

P-glycoprotein/ABCB1 Inducers

May decrease the serum concentration of Letermovir.

Pimozide

Letermovir may increase the serum concentration of Pimozide.

Pitavastatin

Letermovir may increase the serum concentration of Pitavastatin.

Revefenacin

OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin.

Simeprevir

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.

Simvastatin

Letermovir may increase the serum concentration of Simvastatin.

Thioridazine

May diminish the therapeutic effect of Letermovir.

UGT1A1 Inducers

Letermovir may increase the serum concentration of UGT1A1 Inducers.

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.

Voxilaprevir

OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir.