Letermovir

Common name: letermovir tablets

Trade name: Prevymis

All names: letermovir tablets, letermovir, Prevymis, letermovir

Indications:

For use in adult recipients (R+) of allogeneic hematopoietic stem cell transplantation (allo-HSCT) who are seropositive for cytomegalovirus (CMV) to prevent CMV reactivation and infectious diseases.

Usage and dosage:

Take 480mg orally once a day.

Adverse Reactions:

The most common adverse reactions:

Nausea, diarrhea, vomiting, peripheral edema, cough, headache, fatigue, abdominal pain and.

Contraindications:

Concomitant use of pimozide.

Coadministration of pitavastatin and simvastatin.

Take cyclosporine at the same time.

Notes:

Drug interactions may cause adverse reactions or reduce efficacy: Letermovir may potentially interact with certain drugs, causing serious adverse reactions or reducing efficacy: such as with the antiarrhythmic drug amiodarone hydrochloride, the anticoagulant warfarin sodium, and the anticonvulsant phenytoin. sodium), the antidiabetic drugs metformin, glyburide, repaglinide and rosiglitazone tartrate), antifungal drug voriconazole, antimicrobial drug rifampin, antipsychotic drug pimozide, ergot alkaloids, ergotamine caffeine (ergotamine), dihydroergotamine tartrate (dihydroergotamine tartrate), HMG-COA reductase inhibitor (hydroxymethylglutaryl coenzyme reductase inhibitor) a,HMG-COA reductase inhibitor), atorvastatin calcium, pitavastatin calcium, simvastatin, fluvastatin sodium Sodium, lovastatin, pravastatin sodium and rosuvastatin calcium, immunosuppressive drugs cyclosporine, sirolimus and tacrolimus, proton pump inhibitors omeprazole and pantoprazole sodium and other oral preparations are used together.

Pregnancy use: There are insufficient human data to assess the risk of letermovir to pregnant women. Animal reproduction studies have shown that when pregnant rats were fed letermovir 0, 10, 50 or 250 mg·kg-1·d-1 on days 6 to 17 of pregnancy, 250 In the mg·kg-1·d-1 dose group, estimated by AUC, it was about 11 times the RHD, causing embryonic development toxicity, skeletal deformities and umbilical cord shortening. In addition, maternal toxicity caused fetal body weight loss and skeletal deformities. The dose of 50 mg·kg-1·d-1 was about 3 times the RHD, and there was no embryotoxicity. Pregnant rabbits were fed 0, 25, 75 or 225 mg·kg-1·d-1 on the 6th to 20th days of pregnancy respectively. The 225 mg·kg-1·d-1 dose group was about 2 times the RHD, and embryonic development toxicity occurred, including spontaneous abortion, increased post-implantation loss rate and skeletal deformities, while 75 mg·kg-1·d-1, slightly less than RHD, no embryotoxicity. Pregnant rats were fed 0, 10, and 45 mg on the 6th day of prenatal gestation or the 22nd day of postpartum lactation. Or 180 mg·kg-1·d-1. In the 180 mg·kg-1·d-1 dose group, it was about 2 times the RHD. On the 4th day of postpartum or lactation, 5 of 23 pregnant female mice had stillbirths or the total number of litters was reduced due to maternal negligence. The surviving offspring's auricles expanded, their body weight decreased, and the female mice's vaginal openings were retarded. The 45 mg·kg-1·d-1 dose group was approximately similar to the RHD and had no embryotoxicity.

Drugs during lactation: It is unclear whether letermovir is present in human milk and has any effect on milk production or feeding the baby. Give lactating rats intravenous injection of letermovir for 10 days on the 10th day of postpartum lactation period. mg·kg-1, letermovir can still be detected in the blood of maternal rats nursing their pups on the 21st day of postpartum lactation. Whether to breastfeed the infant should weigh the healthy development of the nursing infant and the mother's clinical treatment needs, as well as the potential adverse effects on the infant from letermovir or the mother's illness.

Usage for male and female patients with reproductive potential: There is no data showing that letermovir affects human fertility, but testicular toxicity has been observed in male mice's reproductive experiments, which will reduce fertility.

Dose for patients with renal impairment: CLcr>10 mL·(min)-1, no dosage adjustment is required. For patients with end-stage renal disease, CLcr<10 mL·(min)-1 and patients undergoing hemodialysis, the pharmacokinetic parameters are not yet clear and the medication is not recommended for the time being. CLcr<50 mL·(min)-1 patients receive intravenous injection of letermovir. Its excipient, hydroxypropyl β-cyclodextrin complex, may accumulate in the renal tubules, and the patient's serum creatinine level should be closely monitored.

Usage in patients with liver damage: No dose adjustment is required for patients with mild liver damage (Child-Pugh Class A) or moderate liver damage (Child-Pugh Class B). It is not recommended for patients with severe liver damage (Child-Pugh Class B). Grade C)

Storage:

Store at 20°C to 25°C (68°F to 77°F); excursions allowed at 15°C to 30°C (59°F to 50°F (86°F))

Store in original carton to protect from exposure to light.

Mechanism of action:

Letermovir is an antiviral drug that belongs to a new class of non-nucleoside CMV inhibitors (3,4-dihydroquinazoline). It inhibits viral replication by targeting the viral terminase (terminase) complex.

Safety and Efficacy:

Data showed that a significantly lower proportion of patients in the letermovir-treated group developed a clinically significant CMV infection within 24 weeks of transplantation compared with the placebo group (37.5% [n=122/325] vs 60.6% [n=103/170]; treatment difference: -23.5% [95% CI: -32.5, -14.6]; one-sided test p<0.0001), reaching the primary efficacy endpoint. Additionally, letermovir prophylaxis was associated with lower all-cause mortality within 24 weeks after transplantation (9.8% [n=32/325] vs 15.9% [n=27/170]; log-rank test p =0.0317).