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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PREVYMIS (PREVYMIS).
| Breastfeeding | No human data on breastfeeding; excreted in rat milk. M/P ratio unknown. Caution advised; use only if clearly needed. |
| 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. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["Coadministration with pimozide or ergot alkaloids","Coadministration with atorvastatin (due to increased risk of myopathy/rhabdomyolysis)","Coadministration with strong and moderate CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's wort)"]
| 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)"] |
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| Fertility Effects | No human data on fertility effects. In animal studies, no adverse effects on male or female fertility observed. |