PREVYMIS

(letermovir) 240 mg, 480 mg tablets; Injection 20 mg/mL

Frequently Asked Questions about PREVYMIS

For answers to questions you may have, select any of the topics below. To see a complete list of Q&As, scroll down.

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

  • The recommended dosage of PREVYMIS is 480 mg administered orally or intravenously once daily.

    • Please see full Prescribing Information for proper preparation and administration of PREVYMIS IV infusion.
    • If coadministered with cyclosporine, the recommended dose of PREVYMIS is 240 mg once daily.
    • Start PREVYMIS as early as day 0 and no later than day 28 post-transplant and continue through day 100 post-transplant.
    • PREVYMIS can be initiated before or after engraftment.
    • Following the completion of PREVYMIS prophylaxis, monitoring for CMV reactivation is recommended.

    • PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids.
      • Increased pimozide concentrations may lead to QT prolongation and torsades de pointes.
      • Increased ergot alkaloids concentrations may lead to ergotism.
    • PREVYMIS is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine. Significantly increased pitavastatin or simvastatin concentrations may lead to myopathy or rhabdomyolysis.
    • The concomitant use of PREVYMIS and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug. Consider the potential for drug interactions prior to and during PREVYMIS therapy; review concomitant medications during PREVYMIS therapy; and monitor for adverse reactions associated with PREVYMIS and concomitant medications.
    • The cardiac adverse event rate (regardless of investigator-assessed causality) was higher in subjects receiving PREVYMIS than placebo (13% vs 6%). The most common cardiac adverse events were tachycardia (reported in 4% PREVYMIS subjects and 2% placebo subjects) and atrial fibrillation (reported in 3% PREVYMIS subjects and 1% placebo subjects). Among those subjects who experienced one or more cardiac adverse events, 85% of PREVYMIS and 92% of placebo subjects had events reported as mild or moderate in severity.
    • The rate of adverse events occurring in at least 10% of PREVYMIS-treated HSCT recipients and at a frequency at least 2% greater than placebo were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
    • The most frequently reported adverse event that led to study drug discontinuation was nausea (occurring in 2% of PREVYMIS subjects and 1% of placebo subjects). Hypersensitivity reaction, with associated moderate dyspnea, occurred in one subject following the first infusion of IV PREVYMIS after switching from oral PREVYMIS, leading to treatment discontinuation.
    • Co-administration of PREVYMIS with drugs that are inhibitors of organic anion-transporting polypeptide 1B1/3 (OATP1B1/3) transporters may result in increases in letermovir plasma concentrations.
    • Co-administration of PREVYMIS with inducers of transporters (e.g. P-gp) and/or enzymes (e.g. UGTs) is not recommended due to the potential for a decrease in letermovir plasma concentrations.
    • Co-administration of PREVYMIS with midazolam results in increased midazolam plasma concentrations. Co-administration of PREVYMIS with drugs that are CYP3A substrates may result in clinically relevant increases in the plasma concentrations of co-administered CYP3A substrates.
    • Co-administration of PREVYMIS with drugs that are substrates of OATP1B1/3 transporters may result in a clinically relevant increase in plasma concentrations of co-administered OATP1B1/3 substrates.
    • The magnitude of CYP3A- and OATP1B1/3-mediated drug interactions on co-administered drugs may be different when PREVYMIS is co-administered with cyclosporine. See the prescribing information for cyclosporine for information on drug interactions with cyclosporine.
    • If dose adjustments of concomitant medications are made due to treatment with PREVYMIS, doses should be readjusted after PREVYMIS treatment is completed.
    • Drug interactions may occur based on results from studies. Drug interactions may also occur based on predicted interactions. Potentially significant drug interactions include, but are not limited to, the following (information below applies to co-administration of PREVYMIS and the concomitant drug without cyclosporine, unless otherwise indicated):

      • Anti-arrhythmic Agents
        • Amiodarone: increases ↑amiodarone concentration
      • Antibiotics
        • Nafcillin: decreases ↓letermovir concentration
      • Anticoagulants
        • Warfarin: decreases ↓warfarin concentration
      • Anticonvulsants
        • Carbamazepine: decreases ↓letermovir concentration
        • Phenobarbital: decreases ↓letermovir concentration
        • Phenytoin: decreases ↓both phenytoin and letermovir concentrations
      • Antidiabetic Agents
        • Glyburide: increases ↑glyburide concentration
        • Repaglinide: increases ↑repaglinide concentration
        • Rosiglitazone: increases ↑rosiglitazone concentration
      • Antifungals
        • Voriconazole: decreases ↓voriconazole concentration
      • Antimycobacterials
        • Rifabutin: decreases ↓letermovir concentration
        • Rifampin: decreases ↓letermovir concentration
      • Antipsychotics
        • Pimozide: increases ↑pimozide concentration; co-administration is contraindicated
        • Thioridazine: decreases ↓letermovir concentration
      • Endothelin Antagonists
        • Bosentan: decreases ↓letermovir concentration
      • Ergot Alkaloids
        • Ergotamine: increases ↑ergotamine concentration; co-administration is contraindicated
        • Dihydroergotamine: increases ↑dihydroergotamine concentration; co-administration is contraindicated
      • Herbal Products
        • St. John's wort (Hypericum perforatum): decreases ↓letermovir concentration
      • HIV Medications
        • Efavirenz: decreases ↓letermovir concentration
        • Etravirine: decreases ↓letermovir concentration
        • Nevirapine: decreases ↓letermovir concentration
      • HMG-CoA Reductase Inhibitors
        • Pitavastatin, simvastatin: increases ↑HMG-CoA reductase inhibitors concentration; co-administration is contraindicated when PREVYMIS is co-administered with cyclosporine
        • Atorvastatin: increases ↑atorvastatin concentration
        • Fluvastatin, lovastatin, pravastatin, rosuvastatin: increases ↑HMG-CoA reductase inhibitors concentration
      • Immunosuppressants
        • Cyclosporine: increases ↑both cyclosporine and letermovir concentrations
        • Sirolimus: increases ↑sirolimus concentration
        • Tacrolimus: increases ↑tacrolimus concentration
      • Proton Pump Inhibitors
        • Omeprazole: decreases ↓omeprazole concentration
        • Pantoprazole: decreases ↓pantoprazole concentration
      • Wakefulness-Promoting Agents
        • Modafinil: decreases ↓letermovir concentration
      • CYP3A Substrate Examples
        • Alfentanil, fentanyl, midazolam and quinidine: may increase ↑CYP3A substrate concentration
        • Pimozide and ergot alkaloids are contraindicated
    • The safety and efficacy of PREVYMIS in patients below 18 years of age have not been established.
    • For patients with creatinine clearance (CLcr) greater than 10 mL/min (by Cockcroft-Gault equation), no dosage adjustment of PREVYMIS is required based on renal impairment. The safety of PREVYMIS in patients with end-stage renal disease (CLcr less than 10 mL/min), including patients on dialysis, is unknown.
    • No dosage adjustment of PREVYMIS is required based on mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) hepatic impairment. PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment.
  • Yes. The Merck Access Program for PREVYMIS may be able to help answer questions about insurance coverage for patients, benefit investigations, and the prior authorization and appeals process.

    Click to The Merck Access Program for PREVYMIS

  • Yes. Eligible privately insured patients may pay as little as $15 per prescription on each of up to 4 qualifying prescriptions for up to a one-month's supply per prescription. Maximum savings is $2,500 per prescription.

    Your patients can visit PREVYMIS.com to request a coupon, and if eligible, activate and bring to their pharmacy along with their prescription.

    Not valid for patients who are uninsured or patients with Medicare or other Government Program insurance. Not all patients are eligible. Certain restrictions apply. Tell your eligible, privately insured patients to visit PREVYMIS.com to review the Terms and Conditions.

    Also, eligible health care professionals may request coupons for PREVYMIS for use with their appropriate patients.

    Request coupons for PREVYMIS

  • Yes. HSCT patients are at increased risk for CMV infection, disease, and associated mortality.1–4

    Positive CMV serostatus pre-HSCT is a strong predictor of CMV infection and disease.1,2

    • CMV infection has been shown to occur after allogeneic HSCT in approximately ~65% to 80% of CMV-seropositive patients without CMV prophylaxis.2,3
    • More than 30% of HSCT patients who were CMV-seropositive or had a seropositive donor had CMV infection within 1 month post-transplant.4

    Any level of CMV viremia is associated with an increased risk of mortality in R+ allogeneic HSCT patients in the first year post-HSCT.4,a

    View Clinical Data page for more information

    References

    1. George B, Pati N, Gilroy N, et al. Pre-transplant cytomegalovirus (CMV) serostatus remains the most important determinant of CMV reactivation after allogeneic hematopoietic stem cell transplantation in the era of surveillance and preemptive therapy. Transpl Infect Dis. 2010;12(4):322–329.
    2. Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in hematopoietic stem cell transplant recipients. Hematol Oncol Clin North Am. 2011;25(1):151–169.
    3. Sousa H, Boutolleau D, Ribeiro J, et al. Cytomegalovirus infection in patients who underwent allogeneic hematopoietic stem cell transplantation in Portugal: a five-year retrospective review. Biol Blood Marrow Transplant. 2014;20(12):1958–1967.
    4. Green ML, Leisenring W, Xie H, et al. Cytomegalovirus viral load and mortality after haematopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study. Lancet Haematol. 2016;3(3):e119–e127.

  • Yes. PREVYMIS demonstrated significant efficacy vs placebo in the primary endpoint: Clinically significant CMV infectiona at week 24 (NC=F approach)b. See full clinical data and end points at the link below.

    View study data on the efficacy of PREVYMIS

    (a) Clinically significant CMV infection was defined as either the occurrence of CMV end-organ disease or initiation of anti-CMV PET, based on documented CMV viremia and the clinical condition of the patient. Viremia was determined using the Roche COBAS® AmpliPrep/COBAS TaqMan® assay; lower limit of quantification was 137 IU/mL, which is approximately 150 copies/mL.
    (b) The Noncompleter=Failure (NC=F) approach was used in which patients who discontinued from the study prior to week 24 post-transplant or had a missing outcome at week 24 post-transplant were counted as failures.

  • Adverse events (AE) profile

    Cardiac AEs

    The cardiac AE rate (regardless of investigator-assessed causality) was higher in subjects receiving PREVYMIS (13%) compared to subjects receiving placebo (6%). The most common cardiac AEs were tachycardia (reported in 4% of PREVYMIS subjects and in 2% of placebo subjects) and atrial fibrillation (reported in 3% of PREVYMIS subjects and in 1% of placebo subjects). Among those subjects who experienced 1 or more cardiac AEs, 85% of PREVYMIS and 92% of placebo subjects had events reported as mild or moderate in severity.

    All grade AEs reported in ≥10% of patients treated with PREVYMIS at a frequency at least 2% greater than placebo

    AEs PREVYMIS (n=373) Placebo (n=192)
    Nausea 27% 23%
    Diarrhea 26% 24%
    Vomiting 19% 14%
    Peripheral edema 14% 9%
    Cough 14% 10%
    Headache 14% 9%
    Fatigue 13% 11%
    Abdominal pain 12% 9%

    Drug-related renal and hepatic AEs1

    AEs PREVYMIS Placebo
    Renal and urinary disorders 1% 1%
    Hepatobiliary disorders 0% 1%

    Rates of discontinuation due to AEs were comparable between PREVYMIS and placebo (13% vs 12%, respectively)1


    No differences in incidence of or time to engraftmenta between PREVYMIS and placebo


    (a) Engraftment was defined as an absolute neutrophil count ≥500/mm3 on 3 consecutive days after transplantation.

    Reference

    1. Data available on request from Merck Professional Services-DAP, WP1, PO Box 4, West Point, PA 19486-0004. Please specify information package US-CYT-00438.

  • Yes. Please see additional professional resources and medical education videos on the Professional Resources page, at the link below. There you can learn and understand about early CMV reactivation, identify appropriate patients for prophylaxis with PREVYMIS, and view clinical data for PREVYMIS.

    Click here to view Professional Resources

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Indication

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

Selected Safety Information

  • PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids.
    • Increased pimozide concentrations may lead to QT prolongation and torsades de pointes. 
    • Increased ergot alkaloids concentrations may lead to ergotism.
  • PREVYMIS is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine. Significantly increased pitavastatin or simvastatin concentrations may lead to myopathy or rhabdomyolysis.
  • The concomitant use of PREVYMIS and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug. Consider the potential for drug interactions prior to and during PREVYMIS therapy; review concomitant medications during PREVYMIS therapy; and monitor for adverse reactions associated with PREVYMIS and concomitant medications.
  • The cardiac adverse event rate (regardless of investigator-assessed causality) was higher in subjects receiving PREVYMIS than placebo (13% vs 6%). The most common cardiac adverse events were tachycardia (reported in 4% PREVYMIS subjects and 2% placebo subjects) and atrial fibrillation (reported in 3% PREVYMIS subjects and 1% placebo subjects). Among those subjects who experienced one or more cardiac adverse events, 85% of PREVYMIS and 92% of placebo subjects had events reported as mild or moderate in severity.
  • The rate of adverse events occurring in at least 10% of PREVYMIS-treated HSCT recipients and at a frequency at least 2% greater than placebo were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
  • The most frequently reported adverse event that led to study drug discontinuation was nausea (occurring in 2% of PREVYMIS subjects and 1% of placebo subjects). Hypersensitivity reaction, with associated moderate dyspnea, occurred in one subject following the first infusion of IV PREVYMIS after switching from oral PREVYMIS, leading to treatment discontinuation.
  • Co-administration of PREVYMIS with drugs that are inhibitors of organic anion-transporting polypeptide 1B1/3 (OATP1B1/3) transporters may result in increases in letermovir plasma concentrations.
  • Co-administration of PREVYMIS with inducers of transporters (e.g. P-gp) and/or enzymes (e.g. UGTs) is not recommended due to the potential for a decrease in letermovir plasma concentrations.
  • Co-administration of PREVYMIS with midazolam results in increased midazolam plasma concentrations. Co-administration of PREVYMIS with drugs that are CYP3A substrates may result in clinically relevant increases in the plasma concentrations of co-administered CYP3A substrates.
  • Co-administration of PREVYMIS with drugs that are substrates of OATP1B1/3 transporters may result in a clinically relevant increase in plasma concentrations of co-administered OATP1B1/3 substrates.
  • The magnitude of CYP3A- and OATP1B1/3-mediated drug interactions on co-administered drugs may be different when PREVYMIS is co-administered with cyclosporine. See the prescribing information for cyclosporine for information on drug interactions with cyclosporine.
  • If dose adjustments of concomitant medications are made due to treatment with PREVYMIS, doses should be readjusted after PREVYMIS treatment is completed.
  • Drug interactions may occur based on results from studies. Drug interactions may also occur based on predicted interactions. Potentially significant drug interactions include, but are not limited to, the following (information below applies to co-administration of PREVYMIS and the concomitant drug without cyclosporine, unless otherwise indicated):

    • Anti-arrhythmic Agents
      • Amiodarone: increases ↑amiodarone concentration
    • Antibiotics
      • Nafcillin: decreases ↓letermovir concentration
    • Anticoagulants
      • Warfarin: decreases ↓warfarin concentration
    • Anticonvulsants
      • Carbamazepine: decreases ↓letermovir concentration
      • Phenobarbital: decreases ↓letermovir concentration
      • Phenytoin: decreases ↓both phenytoin and letermovir concentrations
    • Antidiabetic Agents
      • Glyburide: increases ↑glyburide concentration
      • Repaglinide: increases ↑repaglinide concentration
      • Rosiglitazone: increases ↑rosiglitazone concentration
    • Antifungals
      • Voriconazole: decreases ↓voriconazole concentration
    • Antimycobacterials
      • Rifabutin: decreases ↓letermovir concentration
      • Rifampin: decreases ↓letermovir concentration
    • Antipsychotics
      • Pimozide: increases ↑pimozide concentration; co-administration is contraindicated
      • Thioridazine: decreases ↓letermovir concentration
    • Endothelin Antagonists
      • Bosentan: decreases ↓letermovir concentration
    • Ergot Alkaloids
      • Ergotamine: increases ↑ergotamine concentration; co-administration is contraindicated
      • Dihydroergotamine: increases ↑dihydroergotamine concentration; co-administration is contraindicated
    • Herbal Products
      • St. John's wort (Hypericum perforatum): decreases ↓letermovir concentration
    • HIV Medications
      • Efavirenz: decreases ↓letermovir concentration
      • Etravirine: decreases ↓letermovir concentration
      • Nevirapine: decreases ↓letermovir concentration
    • HMG-CoA Reductase Inhibitors
      • Pitavastatin, simvastatin: increases ↑HMG-CoA reductase inhibitors concentration; co-administration is contraindicated when PREVYMIS is co-administered with cyclosporine
      • Atorvastatin: increases ↑atorvastatin concentration
      • Fluvastatin, lovastatin, pravastatin, rosuvastatin: increases ↑HMG-CoA reductase inhibitors concentration
    • Immunosuppressants
      • Cyclosporine: increases ↑both cyclosporine and letermovir concentrations
      • Sirolimus: increases ↑sirolimus concentration
      • Tacrolimus: increases ↑tacrolimus concentration
    • Proton Pump Inhibitors
      • Omeprazole: decreases ↓omeprazole concentration
      • Pantoprazole: decreases ↓pantoprazole concentration
    • Wakefulness-Promoting Agents
      • Modafinil: decreases ↓letermovir concentration
    • CYP3A Substrate Examples
      • Alfentanil, fentanyl, midazolam and quinidine: may increase ↑CYP3A substrate concentration
      • Pimozide and ergot alkaloids are contraindicated
  • The safety and efficacy of PREVYMIS in patients below 18 years of age have not been established.
  • For patients with creatinine clearance (CLcr) greater than 10 mL/min (by Cockcroft-Gault equation), no dosage adjustment of PREVYMIS is required based on renal impairment. The safety of PREVYMIS in patients with end-stage renal disease (CLcr less than 10 mL/min), including patients on dialysis, is unknown.
  • No dosage adjustment of PREVYMIS is required based on mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) hepatic impairment. PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment.

Before prescribing PREVYMIS, please read the accompanying Prescribing Information. The Patient Information also is available.

US-CYT-0101810/21