Instructions for use and marketing status of Letermovir

1. Generic name: Letermovir, Letermovir

Product name: Premin, Prevymis

2. Indications:

Letermovir is indicated to treat the following conditions:

1. Cytomegalovirus prophylaxis in hematopoietic stem cell transplant (HSCT) recipients: Indicated for the prevention of cytomegalovirus (CMV) infection and disease in adult and pediatric patients aged 6 months and older and weighing at least 6 kg who have received a CMV-seropositive allogeneic hematopoietic stem cell transplant [R+].

2. Cytomegalovirus prevention in kidney transplant recipients: It is suitable for preventing CMV disease in adult and pediatric patients aged 12 years and above and weighing at least 40 kg. These patients are high-risk kidney transplant recipients (donor CMV seropositive/recipient CMV seronegative [D+/R-]).

3. Usage and dosage:

1. Medication instructions: Letermovir is available in 3 dosage forms: tablets, injections, and oral granules; it is taken orally and can be taken on an empty stomach or with food. The tablet should be swallowed whole and should not be broken, crushed, or chewed. When combined with cyclosporine, the dosage of this product should be adjusted; after completing the prophylactic course of this product, it is recommended to monitor CMV reactivation in HSCT recipients.

2. Recommended dosage:

(1)Adult recipients of allogeneic hematopoietic stem cell transplant (HSCT) and Pediatric patients 12 years and above and weighing at least 30kg; Or adult recipients of kidney transplants andPediatric patients 12 years and above and weighing at least 40kg Pediatric patients:

1) After HSCT transplantation: Each time480mg (tablet) , taken orally, once a day. Start taking this product on the day after surgery or no later than 28 days after surgery, and continue to take it until 100 days after transplantation; If the patient has a recent risk ofCMV infection and disease, continue to take it until 200 days after transplantation.

2) After kidney transplantation: each time480mg (tablet) , taken orally, once a day. Start taking this product on the day after surgery or no later than 7 days after surgery, and continue to take it until 200 days after transplantation.

（2）AgeHSCT transplant recipients over 6 months old to under 12 years old and weighing at least 30kg: The dose is calculated based on the patient's weight(see below), taken orally, once daily, and continued to be taken until 100 days after transplantation; If the patient has a recent risk ofCMV infection and disease, continued to be taken until 200 days after transplantation.

-Weight 30kg and above: each time480mg, once a day, orally;

-Weight between 15kg and 30kg: each time240mg, once a day, orally;

-Weight 7.5kg to less than 15kg: Recommended to take once a day One pack of 120mg oral granules or 60mg intravenous injection once a day;

-Weight 6kg to 7.5kg or less: Recommended to be taken once dailyFour packs20mg oral granules or dailyonce 40mg intravenous injection.

4. Adverse reactions:

In clinical studies of letermovir, adverse reactions may include nausea, vomiting, diarrhea, abdominal pain, headache, fatigue, cough, and edema. In general, the drug's adverse effects were comparable to those seen with placebo treatment.

5. Supply and storage:

1. Tablets: including 240mg and 480mg tablets; before use, keep the temovir tablets in the original packaging to prevent moisture. Store at20°C to 25°C (68°F to 77°F); excursions allowed within 15°C to 30°C (59°F to 86°F).

2. Oral granules: including 20mg and 120mg oral granules, which can be stored in the temperature range of 20°C to 25°C (68°F to 77°F); excursions are allowed between 15°C to 30°C (59°F to 86°F).

3. Injection: Letermovir is a sterile, transparent, colorless solution for intravenous injection, with a concentration of 240mg/12mL (20mg/mL) or 480mg/2 4 mL (20 mg/L); store vial at 20°C to 25°C (68°F to 77°F); excursions allowed within 15°C to 30°C (59°F to 86°F). Please store in original carton to avoid exposure to light.

6. Mechanism of action:

Letermovir inhibits the CMV DNA terminase complex (pUL51, pUL56 and pUL89) required for viral DNA processing and packaging. Biochemical characterization and electron microscopy demonstrated that letomovir affects the production of appropriate unit length genomes and interferes with virion maturation. Genotypic characterization of letermovir-resistant viruses confirms that letermovir targets the terminator complex.

7. Listing situation:

Letermovir was approved for use in the United States by the U.S. Food and Drug Administration (FDA) in January 2017;2 In January 2018, it was approved by the European Medicines Agency (EMA) for use in the EU, with the trade name Prevymis; in December 2021, the National Medical Products Administration approved the use of letermovir tablets in China, with the trade name Prevymis.

Reference materials:https://www.mayoclinic.org/drugs-supplements/letermovir-intravenous-route/description/drg-20406607