PREVYMIS

2. 1. 1 Therapeutic indications PREVYMIS is indicated for prophylaxis of cytomegalovirus (CMV) reactivation and disease in adult CMV-seropositive recipients [R+] of an allogeneic haematopoietic stem cell transplant (HSCT). Consideration should be given to official guidance on the appropriate use of antiviral agents.

2 Posology and method of administration PREVYMIS should be initiated by a physician experienced in the management of patients who have had an allogeneic haematopoietic stem cell transplant. Posology PREVYMIS is also available for oral administration (240 mg and 480 mg film-coated tablets).

PREVYMIS tablets and concentrate for solution for infusion may be used interchangeably at the discretion of the physician, and no dose adjustment is necessary. The recommended dosage of PREVYMIS is 480 mg once daily. PREVYMIS should be started after HSCT.

PREVYMIS may be started on the day of transplant and no later than 28 days post-transplant. PREVYMIS may be started before or after engraftment. Prophylaxis with PREVYMIS should continue through 100 days post-transplant. The safety and efficacy of letermovir use for more than 100 days has not been studied in clinical trials.

1). Use of letermovir prophylaxis for greater than 100 days requires a careful assessment of the benefit-risk balance. 2). • If ciclosporin is initiated after starting PREVYMIS, the next dose of PREVYMIS should be decreased to 240 mg once daily.

• If ciclosporin is discontinued after starting PREVYMIS, the next dose of PREVYMIS should be increased to 480 mg once daily. • If ciclosporin dosing is temporarily interrupted due to high ciclosporin levels, no dose adjustment of PREVYMIS is needed.

Missed dose If a dose is missed, it should be given to the patient as soon as possible. If it is time for the next dose, skip the missed dose and go back to the regular schedule. Do not double the next dose or give more than the prescribed dose.

2). Hepatic impairment No dose adjustment of PREVYMIS is required based on mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) hepatic impairment. 2). 2). Renal impairment No dose adjustment of PREVYMIS is recommended for patients with mild, moderate, or severe renal impairment.

No dose recommendation can be made for patients with end stage renal disease (ESRD) with or without dialysis. Efficacy and safety has not been demonstrated for patients with ESRD. PREVYMIS concentrate for solution for infusion contains hydroxypropylbetadex.

The anticipated clinical exposure to hydroxypropylbetadex with intravenously administered letermovir is expected to be approximately 3,600 mg/day for a letermovir dose of 480 mg. There were no cases of kidney injury caused by hydroxypropylbetadex in human studies of intravenously administered letermovir with treatment durations of up to 47 days.

3). Serum creatinine levels should be closely monitored in these patients. Paediatric population The safety and efficacy of PREVYMIS in patients below 18 years of age have not been established. 1). Method of administration For intravenous use only.

6) prior to administration. 22 micron polyethersulfone (PES) in-line filter. 22 micron PES in-line filter. PREVYMIS should be administered as an intravenous (IV) infusion only. PREVYMIS should not be administered as an intravenous push or bolus.

After dilution, PREVYMIS should be administered by intravenous infusion via peripheral or central venous catheter using a total time of approximately 60 minutes. The entire contents of the IV bag should be administered.

1). 9%). 5%). Tabulated summary of adverse reactions The following adverse reactions were identified in patients taking PREVYMIS 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 PREVYMIS 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 Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Monitoring of CMV DNA The safety and efficacy of letermovir has been established in 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 PREVYMIS 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). 22 micron PES in-line filter PREVYMIS concentrate for solution for infusion may contain a few product-related small translucent or white particles. 6). 0 mmol) sodium per dose. This should be taken into consideration by patients on a controlled sodium diet.

0 mmol) sodium per dose. This should be taken into consideration by patients on a controlled sodium diet.

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