Prevymis
Prevymis Uses, Dosage, Side Effects, Food Interaction and all others data.
Prevymis recieved approval from the FDA on November 8th, 2017 for use in prophylaxis of cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplant patients . It represents the first entry into a new class of CMV anti-infectives, DNA terminase complex inhibitors . Prevymis has recieved both priority and orphan drug status from the FDA. It is currently marketed under the brand name Prevymis .
Prevymis inhibits the activity of the DNA terminase complex of CMV thereby preventing the cutting of viral DNA into mature length genomes for packaging into viral particles . Letemovir inhibits the DNA terminase complex with an EC50 of 2.1nM.
| Trade Name | Prevymis |
| Availability | Prescription only |
| Generic | Letermovir |
| Letermovir Other Names | Letermovir |
| Related Drugs | valacyclovir, ganciclovir, valganciclovir, Valcyte, Prevymis, Cytovene |
| Weight | 240mg/12ml, 480mg/24ml, 240mg, 480mg, |
| Type | Infusion, Intravenous Solution, Oral Tablet, Oral/injection, Intravenous |
| Formula | C29H28F4N4O4 |
| Weight | Average: 572.561 Monoisotopic: 572.20466805 |
| Protein binding | Letermovir has been observed to be 99% bound to plasma proteins at concentrations of 0.2-50 mg/L in vitro . |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | Merck Sharp & Dohme (UK) Limited |
| Available Country | Australia, Canada, United Kingdom, United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Prevymis is an antiviral medication used to treat CMV infections and disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT).
For use in prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT) .
Prevymis is also used to associated treatment for these conditions: Cytomegalovirus (CMV) Infection
How Prevymis works
CMV relies on a DNA terminase complex consisting of multiple subunits (pUL51, pUL56, and pUL89) for processing of viral DNA. Viral DNA is produced in a single repeating strand which is then cut by the DNA terminase complex into individual viral genomes which can then be packaged into mature viral particles . Letemovir inhibits the activity of this complex to prevent production of mature viral genomes and the production of viable viral particles. The exact nature of Letemovir's binding to this complex is not currently known. Initially, the observation of resistance-causing mutations in pUL56 suggested this subunit was the location of Letemovir binding . However, resistance mutations have now been observed in pUL51, pUL56, and pUL89 . It is possible that changes in amino acid sequence in one subunit could result in conformational changes to interacting subunits affecting Letemovir binding or that Letemovir interacts with multiple subunits of the complex but evidence towards either of these distinctions has not yet been seen. pUL89 is known to contain the endonuclease activity of the complex but because all members of the complex are necessary for targeting as well as protection from proteosomal degradation, it is difficult to discern if Letemovir inhibits pUL89's activity directly .
Toxicity
There is no human data on the safety of Letemovir in pregnancy . Embryo-fetal toxicity and malformations have been observed in rats at exposures 11 times the human exposure at the recommended human dose (RHD) of Letemovir. No such toxicity was noted in rats at 3 times human exposure at the RHD or in rabbits at values less than human exposure with the RHD. Total litter loss was observed in 21.7% of female rats at 2 times human exposure at RHD. This did not occur at values similar to human exposure at RHD.
No human data is available regarding lactation . Letemovir has been observed in the milk of lactating rats and in the blood of their nursing pups.
No data is available concerning the effect of Letemovir on human fertility . Testicular toxicity leading to reduced fertility has been observed in male rats.
No antidote exists for Letemovir overdosage . The effectiveness of dialysis in clearing plasma of Letemovir is unknown.
Food Interaction
- Avoid St. John's Wort. Co-administration may lead to decreased serum concentrations of letermovir.
- Take with or without food.
Prevymis Drug Interaction
Moderate: loratadine, fluticasone nasal, tramadol, ondansetronUnknown: charcoal, mycophenolate mofetil, arginine, levocarnitine, cysteine, lithium, pregabalin, bioflavonoids, valproic acid, albuterol, thiamine, cyanocobalamin, pyridoxine, cholecalciferol, phytonadione, menaquinone
Prevymis Disease Interaction
Volume of Distribution
The mean steady state volume of distrubution is 45.5L
Elimination Route
Prevymis has a bioavailability of 94% in healthy subjects when administered without cyclosporin, 35% in HSCT recipients when administered without cyclosporin, and 85% in HSCT recipients when administered with cyclosporin .
Prevymis's Tmax is 45 min to 2.25 h . Time to steady state has been observed to be 9-10 days.
Taking Prevymis with food increases Cmax by an average of 129.82% (range of 104.35%-161.50%) . No significant effect on AUC has been observed .
Half Life
The mean terminal half-life was observed to be 12 hours following administration of Letemovir 480 mg IV once daily .
Clearance
The mean clearance is 11.25 L/h in healthy subjects
Elimination Route
Letemovir is taken up by the liver through OATP1B1/3 transporters. 93% is excreted in the feces with 70% as the parent drug . <2% is excreted in the urine.
Innovators Monograph
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