PREVYMIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PREVYMIS (PREVYMIS).
Letermovir is an anti-cytomegalovirus (CMV) inhibitor that targets the CMV terminase complex, specifically the pUL56 subunit, thereby preventing cleavage and packaging of viral DNA into capsids, which inhibits viral replication.
| Metabolism | Letermovir is primarily metabolized by UGT1A1/1A3 with minor contributions from CYP3A4. It is also a substrate of OATP1B1/1B3 and P-glycoprotein (P-gp). |
| Excretion | Primarily excreted unchanged in feces via biliary secretion (93%), with renal excretion accounting for <2% of the dose. |
| Half-life | Terminal elimination half-life is approximately 12 hours in healthy subjects, prolonged to ~19 hours in renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 98.8% bound to human plasma proteins, predominantly albumin. |
| Volume of Distribution | Volume of distribution is about 48 L (0.69 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Absolute oral bioavailability is 27% (range 21–33%). |
| Onset of Action | Oral: Steady-state achieved within 6–8 days with once-daily dosing; clinical antiviral effect observed within 1–2 weeks. |
| Duration of Action | Duration of antiviral effect persists for 24 hours (once-daily dosing). Dosing continues through 100 days post-transplant for prophylaxis. |
| Molecular Weight | 572.6 |
480 mg orally once daily, with food.
| Dosage form | PELLETS |
| Renal impairment | For GFR ≥ 30 mL/min: 480 mg once daily. For GFR 10-29 mL/min: 200 mg once daily. For GFR < 10 mL/min (not on hemodialysis): not recommended. |
| Liver impairment | No dose adjustment required for mild or moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | For pediatric patients (≥ 12 years and weighing ≥ 40 kg): 480 mg once daily with food. For < 12 years or weight < 40 kg: safety and efficacy not established. |
| Geriatric use | No specific dose adjustment based solely on age; use renal function to guide dosing. Monitor renal function closely. |
| 1st trimester | Limited human data; animal studies show embryo-fetal toxicity at exposures slightly above clinical exposure. Not recommended unless benefit outweighs risk. |
| 2nd trimester | Limited human data; potential risk based on animal studies. Use only if clearly needed. |
| 3rd trimester | Limited human data; animal studies show possible fetotoxicity. Use only if benefit justifies risk. |
Clinical note
Comprehensive clinical and safety monograph for PREVYMIS (PREVYMIS).
| Placental transfer | Effective in vitro human placental perfusion assay at 0.5 μM, placental transfer index of 0.38. |
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Because of potential for serious adverse reactions, breastfeeding should be discontinued or drug avoided. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Hypersensitivity to letermovir or any component of the formulation
| Precautions | Risk of increased letermovir plasma concentrations when coadministered with cyclosporine, requiring dose reduction of letermovir, Risk of reduced efficacy when coadministered with strong inducers of CYP3A4, UGTs, or P-gp (e.g., rifampin), Potential for drug interactions with immunosuppressants such as tacrolimus, sirolimus, and cyclosporine, necessitating therapeutic drug monitoring, Risk of myelosuppression when used with certain antineoplastic agents, Not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C) |
| Food/Dietary | No significant food interactions; can be taken with or without food. Avoid grapefruit or grapefruit juice as they may increase drug levels. |
Loading safety data…
| Lactation Rating |
| L5 |
| Teratogenic Risk | First trimester: Limited data; animal studies show no evidence of teratogenicity. Second and third trimesters: No known fetal risks; use only if benefit justifies risk. |
| Fetal Monitoring | Monitor for hepatotoxicity (ALT, AST, bilirubin), nephrotoxicity (serum creatinine), and gastrointestinal symptoms. Fetal monitoring per standard obstetric care. |
| Fertility Effects | No human data on fertility effects. In animal studies, no adverse effects on male or female fertility observed. |
| Clinical Pearls | PREVYMIS (letermovir) is a CMV terminase complex inhibitor for prophylaxis in CMV-seropositive hematopoietic stem cell transplant (HSCT) recipients. It has no activity against HSV or VZV. Significant drug interactions occur via CYP3A4 and OATP1B1/3; avoid coadministration with atorvastatin, simvastatin, and significantly reduce pitavastatin dose. Letermovir reduces anti-HIV protease inhibitor and cyclosporine levels; monitor cyclosporine trough and adjust dose. Administer with or without food. Monitor for CYP3A4 induction effect persisting up to 2 weeks after discontinuation. |
| Patient Advice | Take PREVYMIS exactly as prescribed at the same time each day. · Do not stop taking this medication without talking to your doctor; it prevents a serious viral infection. · Inform your doctor about all other medications, especially statins (cholesterol-lowering drugs) and cyclosporine, as dose adjustments may be needed. · If you miss a dose, take it as soon as you remember unless it is within 12 hours of the next dose; do not double dose. · Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Common side effects include nausea, diarrhea, and vomiting; contact your doctor if these become severe. |