Letermovir

Common name: Letermowe tablet

Product name: Prevymis

Full names: letermovir tablets, letermovir, Prevymis, letermovir

Indications:

is used 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:

480mg orally taken once a day.

Adverse reactions:

The most common adverse reactions:

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

Taboo:

Take pimozide at the same time.

Pitavastatin and simvastatin are administered together.

Take cyclosporine at the same time.

Notes:

Drug interactions causing adverse reactions or reducing efficacy: The compatibility of letermovir with certain drugs may have potential interactions, causing serious adverse reactions or reducing efficacy: such as with the antiarrhythmic drug amiodarone hydrochloride, the anticoagulant drug warfarin sodium, the anticonvulsant drug phenytoin sodium, the antidiabetic drug metformin, and glyburide (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 evaluate 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 developmental toxicity, skeletal malformations and umbilical cord shortening. In addition, maternal toxicity caused fetal body weight loss and skeletal malformations. The dose was 50 mg·kg-1·d-1, which was about 3 times the RHD and had no embryotoxicity. Pregnant rabbits were fed 0, 25, 75 or 225 mg·kg-1·d-1, respectively, on days 6 to 20 of pregnancy. The mg·kg-1·d-1 dose group was about 2 times the RHD and showed embryonic developmental toxicity, including spontaneous abortion, increased post-implantation loss rate and skeletal deformities, while the 75 mg·kg-1·d-1 dose group was slightly less than the RHD and had no embryotoxicity. Pregnant rats were fed 0, 10, 45 or 180 mg·kg-1·d-1,180 respectively on the 6th day of prenatal pregnancy or the 22nd day of postpartum lactation. In the mg·kg-1·d-1 dose group, it was about 2 times the RHD. On the 4th day after delivery or on the fourth day of lactation, 5 of 23 pregnant female mice had stillbirths or the total number of litters was reduced due to maternal negligence. The auricles of the surviving offspring expanded, their body weight decreased, and the vaginal opening of female mice was retarded. The 45 mg·kg-1·d-1 dose group was approximately similar to the RHD and had no embryotoxicity.

Lactation medication: It is unknown; whether letermovir is present in human milk and has any effect on milk production or feeding the baby. Letermovir was administered intravenously to lactating rats at 10 mg·kg-1 on the 10th day of postpartum lactation. Letermovir could still be detected in the blood of mothers nursing pups on day 21 of postpartum lactation. Whether to breastfeed the infant should be weighed against 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.

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

Drug for patients with renal impairment: CLcr>10 mL·(min)-1, no dose adjustment is required. For patients with end-stage renal disease, CLcr<10 mL·(min)-1 and patients undergoing hemodialysis, the pharmacokinetic parameters are still unclear and the drug is not recommended for the time being. Patients with CLcr<50 mL·(min)-1 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.

Drugs for patients with liver damage: Patients with mild liver damage (Child-Pugh Class A) Or patients with moderate liver impairment (Child-Pugh Class B) do not need to adjust the dose, and it is not recommended for patients with severe liver impairment (Child-Pugh Class C)

Store:

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

Store in original carton to prevent 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) that inhibits viral replication by targeting the viral terminase (terminase) complex.

Safety and efficacy:

The data showed that compared with the placebo group, a significantly lower proportion of patients in the letermovir-treated group experienced post-transplantation Clinically significant CMV infection within 24 weeks (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).