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Adverse events (AE) in adult HSCT patients

Safety profile through Week 14 (~100 days) post-HSCT in adults

Safety profile from Week 14 (~100 days) through Week 28 (~200 days) post-HSCT in adults

Safety profile through Week 14 (~100 days) post-HSCT in adults

Cardiac AEs

The cardiac AE rate 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

Adverse Events Reported in a Clinical Trial of Adult Patients Receiving PREVYMIS® (letermovir) vs Placebo

Drug-related renal and hepatic AEs1

Drug-Related Renal and Hepatic Adverse Events Reported in a Clinical Trial.

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

No differences in incidence of, or time to, engraftmenta between PREVYMIS and placebo2

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

Safety profile from Week 14 (~100 days) through Week 28 (~200 days) post-HSCT in adults

  • The most commonly reported adverse events with prophylaxis with PREVYMIS from Week 14 through Week 28 post-HSCT were similar to those reported with prophylaxis with PREVYMIS through Week 14 post-HSCT.
  • Study drug was discontinued due to an adverse event in 5% of PREVYMIS subjects and 1% of placebo subjects.
  • The cardiac adverse event rate was 4% in the PREVYMIS and placebo groups.
  • The rates of hematologic laboratory abnormalities were comparable in the PREVYMIS and placebo groups. Serum creatinine abnormalities >1.5 mg/dL occurred in 15% of PREVYMIS and 8% of placebo subjects.

References

  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-01362.
  2. Marty FM, Ljungman P, Chemaly RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017;377(25)(suppl):1-54. Accessed January 5, 2024. http://www.nejm.org/doi/suppl/10.1056/NEJMoa1706640/suppl_file/nejmoa1706640_appendix.pdf

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Indications

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

 

PREVYMIS® is indicated for prophylaxis of CMV disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).

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.
  • Intravenous formulation of PREVYMIS contains the excipient hydroxypropyl betadex. PREVYMIS injection should be used only in patients unable to take oral therapy and patients should be switched to oral PREVYMIS as soon as they are able to take oral medications. If possible, intravenous administration should not exceed 4 weeks.
  • In patients with renal impairment, accumulation of hydroxypropyl betadex may occur. In adult patients with CLcr less than 50 mL/min and in pediatric patients with a similar degree of renal impairment (based on age-appropriate assessment of renal function) receiving PREVYMIS injection, closely monitor serum creatinine levels.
  • Animal studies have shown the potential for hydroxypropyl betadex to cause ototoxicity. The active ingredient, letermovir, is not known to be associated with ototoxicity.
  • The rate of adverse events occurring in at least 10% of adult HSCT recipients treated with PREVYMIS 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%).
  • Hypersensitivity reaction, with associated moderate dyspnea, occurred in one adult HSCT recipient following the first infusion of IV PREVYMIS after switching from oral PREVYMIS, leading to treatment discontinuation.
  • The most common adverse event occurring in at least 10% of adult kidney transplant recipients treated with PREVYMIS and at a frequency greater than valganciclovir was diarrhea (32% vs 29%).
  • If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily.
  • Co-administration of PREVYMIS may alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PREVYMIS. Consult the full Prescribing Information prior to and during treatment for potential drug interactions.
  • Closely monitor serum creatinine levels in patients with CLcr less than 50 mL/min using PREVYMIS injection.
  • PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment.
  • 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.

Before prescribing PREVYMIS® (letermovir), please read the accompanying Prescribing Information. The Patient Information and Instructions for Use also are available.

Indications

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

 

PREVYMIS® is indicated for prophylaxis of CMV disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).

PREVYMIS® (letermovir) is indicated for prophylaxis of cytomegalovirus (CMV) infection and disease in adult

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

PREVYMIS® is indicated for prophylaxis of CMV disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).

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.
  • Intravenous formulation of PREVYMIS contains the excipient hydroxypropyl betadex. PREVYMIS injection should be used only in patients unable to take oral therapy and patients should be switched to oral PREVYMIS as soon as they are able to take oral medications. If possible, intravenous administration should not exceed 4 weeks.
  • In patients with renal impairment, accumulation of hydroxypropyl betadex may occur. In adult patients with CLcr less than 50 mL/min and in pediatric patients with a similar degree of renal impairment (based on age-appropriate assessment of renal function) receiving PREVYMIS injection, closely monitor serum creatinine levels.
  • Animal studies have shown the potential for hydroxypropyl betadex to cause ototoxicity. The active ingredient, letermovir, is not known to be associated with ototoxicity.
  • The rate of adverse events occurring in at least 10% of adult HSCT recipients treated with PREVYMIS 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%).
  • Hypersensitivity reaction, with associated moderate dyspnea, occurred in one adult HSCT recipient following the first infusion of IV PREVYMIS after switching from oral PREVYMIS, leading to treatment discontinuation.
  • The most common adverse event occurring in at least 10% of adult kidney transplant recipients treated with PREVYMIS and at a frequency greater than valganciclovir was diarrhea (32% vs 29%).
  • If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily.
  • Co-administration of PREVYMIS may alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PREVYMIS. Consult the full Prescribing Information prior to and during treatment for potential drug interactions.
  • Closely monitor serum creatinine levels in patients with CLcr less than 50 mL/min using PREVYMIS injection.
  • PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment.
  • 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.

Before prescribing PREVYMIS® (letermovir), please read the accompanying Prescribing Information. The Patient Information and Instructions for Use also are available.

PREVYMIS is contraindicated in patients receiving pimozide or

  • PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids.
    • Increased pimozide concentrations may lead to QT prolongation and torsades de pointes.