Prevymis

Letermovir should be initiated by a physician experienced in the management of patients who have had an allogeneic haematopoietic stem cell transplant or kidney transplant. Posology Letermovir is also available as granules in sachet (20 mg and 120 mg) and as concentrate for solution for infusion (240 mg and 480 mg).

Letermovir tablets, granules in sachet, and concentrate for solution for infusion may be used interchangeably at the discretion of the physician. Dose adjustment may be necessary for paediatric patients weighing less than 30 kg when switching between oral and intravenous formulations.

Refer to the prescribing information for the letermovir concentrate for solution for infusion for dosing information. HSCT Letermovir should be started after HSCT. Letermovir may be started on the day of transplant and no later than 28 days post-HSCT.

Letermovir may be started before or after engraftment. Prophylaxis with letermovir should continue through 100 days post-HSCT. 1). The safety and efficacy of letermovir use for more than 200 days has not been studied in clinical trials.

Adult and paediatric patients weighing at least 30 kg who are HSCT recipients The recommended dose of letermovir is 480 mg once daily that can be administered either as one 480 mg tablet or as two 240 mg tablets. For patients who cannot swallow tablets, refer to the prescribing information for the letermovir granules in sachet for dosing information.

2). • If cyclosporine is initiated after starting letermovir, the next dose of letermovir should be decreased to 240 mg once daily. • If cyclosporine is discontinued after starting letermovir, the next dose of letermovir should be increased to 480 mg once daily.

• If cyclosporine dosing is temporarily interrupted due to high cyclosporine levels, no dose adjustment of letermovir is needed. 2). For paediatric patients who cannot swallow tablets, refer to the prescribing information for letermovir granules in sachet for dosing information.

2). For patients requiring a 120 mg dose, refer to the prescribing information for the letermovir granules in sachet for dosing information. • If cyclosporine is initiated after starting letermovir, the next dose of letermovir should be decreased to 120 mg once daily.

4 • If cyclosporine is discontinued after starting letermovir, the next dose of letermovir should be increased to 240 mg once daily. • If cyclosporine dosing is temporarily interrupted due to high cyclosporine levels, no dose adjustment of letermovir is needed.

Summary of the safety profile The safety assessment of letermovir was based on three Phase 3 clinical trials. 1). 9%). 5%). 1). The adverse reactions reported were consistent with the safety profile of letermovir as characterised in study P001.

1). Tabulated summary of adverse reactions The following adverse reactions were identified in adult patients taking letermovir in clinical trials. The adverse reactions are listed below by body system organ class and frequency. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000) or very rare (< 1/10 000).

Table 2:

Adverse reactions identified with letermovir Frequency Adverse reactions Immune system disorders Uncommon hypersensitivity Metabolism and nutrition disorders Uncommon decreased appetite Nervous system disorders Uncommon dysgeusia, headache Ear and labyrinth disorders Uncommon vertigo Gastrointestinal disorders Common nausea, diarrhoea, vomiting Uncommon abdominal pain Hepatobiliary disorders Uncommon alanine aminotransferase increased, aspartate aminotransferase increased Musculoskeletal and connective tissue disorders Uncommon muscle spasms Renal and urinary disorders Uncommon blood creatinine increased General disorders and administration site conditions Uncommon fatigue, oedema peripheral 19 Paediatric population The safety assessment of letermovir in paediatric patients from birth up to 18 years old was based on a Phase 2b clinical trial (P030).

In P030, 63 HSCT recipients were treated with letermovir through Week 14 post-HSCT. , 28 adolescents, 14 children aged 7 to less than 12 years, 13 aged 2 to less than 7 years, and 8 less than 2 years old (5 of them less than 1 year old).

The adverse reactions were consistent with those observed in clinical studies of letermovir in adults. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

Monitoring of CMV DNA in HSCT recipients In a Phase 3 trial (P001), the safety and efficacy of letermovir has been established in HSCT patients with a negative CMV DNA test result prior to initiation of prophylaxis. CMV DNA was monitored on a weekly basis until post-transplant Week 14, and subsequently every two weeks until Week 24.

In cases of clinically significant CMV DNAemia or disease, letermovir prophylaxis was stopped and standard-of-care pre-emptive therapy (PET) or treatment was initiated. 1). Risk of adverse reactions or reduced therapeutic effect due to medicinal product interactions The concomitant use of letermovir and certain medicinal products may result in known or potentially significant medicinal product interactions, some of which may lead to: • possible clinically significant adverse reactions from greater exposure of concomitant medicinal products or letermovir.

• significant decrease of concomitant medicinal product plasma concentrations which may lead to reduced therapeutic effect of the concomitant medicinal product. 5). , alfentanil, fentanyl, and quinidine) as co-administration may result in increases in the plasma concentrations of CYP3A substrates.

5). 5) as well as after changing route of administration of letermovir. Letermovir is a moderate inducer of enzymes and transporters. 5). Therapeutic drug monitoring (TDM) is therefore recommended for voriconazole. Concomitant use of dabigatran should be avoided due to risk of reduced dabigatran efficacy.

5 and Table 1). Excipients PREVYMIS contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

1. 5). 5). Concomitant administration with St. 5). 5).