PREVYMIS Film-coated tablet Ref.[8782] Active ingredients: Letermovir

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.

Prolonged letermovir prophylaxis beyond 100 days post-HSCT may be of benefit in some patients at high risk for late CMV reactivation (see section 5.1). 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.

Dose adjustment in adult and paediatric patients weighing at least 30 kg who are HSCT recipients

If letermovir is co-administered with cyclosporine, the dose of letermovir should be decreased to 240 mg once daily (see sections 4.5 and 5.2).

• 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.

Paediatric patients weighing at least 15 kg to less than 30 kg who are HSCT recipients

The recommended dose of letermovir is 240 mg once daily that can be administered as one 240 mg tablet (see also section 5.2).

For paediatric patients who cannot swallow tablets, refer to the prescribing information for letermovir granules in sachet for dosing information.

Dose adjustment in paediatric patients weighing at least 15 kg to less than 30 kg who are HSCT recipients

If oral letermovir is co-administered with cyclosporine, the dose of letermovir should be decreased to 120 mg once daily (see also sections 4.5 and 5.2) . 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.
• 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.

Kidney transplant

Letermovir should be started on the day of transplant and no later than 7 days post-kidney transplant and continued through 200 days post-transplant.

Adult and paediatric patients weighing at least 40 kg who are kidney transplant 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 dosi ng information.

Dose adjustment in adult and paediatric patients weighing at least 40 kg who are kidney transplant recipients

If letermovir is co -administered with cyclosporine, the dose of letermovir should be decreased to 240 mg once daily (see sections 4.5 and 5.2).

• 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.

Missed dose

Patients should be instructed that if they miss a dose of letermovir, they should take it as s oon as they remember. If they do not remember until it is time for the next dose, they should skip the missed dose and go back to the regular schedule. Patients should not double their next dose or take more than the prescribed dose.

Special populations

Elderly

No dose adjustment of letermovir is required based on age (see sections 5.1 and 5.2).

Hepatic impairment

No dose adjustment of letermovir is required based on mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) hepatic impairme nt. Letermovir is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment (see section 5.2).

Combined hepatic and renal impairment

Letermovir is not recommended in patients with moderate hepatic impairment combined with moderate or severe renal impairment (see section 5.2).

Renal impairment

No dose adjustment of letermovir is recommended for patients with mild, moderate, or severe renal impairment. No dose recommendation can be made for patients with end stage renal dise ase (ESRD) with or without dialysis. Efficacy and safety has not been demonstrated for patients with ESRD.

Paediatric population

The safety and efficacy of letermovir in HSCT patients weighing less than 5 kg or in kidney transplant patients weighing less than 40 kg have not been established. No data are available. No recommendation on posology for kidney transplant patients weighing less than 40 kg could be supported by pharmacokinetic/pharmacodynamic extrapo lation.

Method of administration

For oral use.

The tablet should be swallowed whole and may be taken with or without food. The tablet should not be divided, crushed, or chewed because these methods have not been studied.

There is no experience with human overdose with letermovir. During Phase 1 clinical trials, 86 healthy adult subjects received doses ranging from 720 mg/day to 1 440 mg/day of letermovir for up to 14 days. The adverse reaction profile was similar to that of the clinical dose of 480 mg/day. There is no specific antidote for overdose with letermovir. In case of overdose, it is recommended that the patient be monitored for adverse reactions and appropriate symptomatic treatment instituted.

It is unknown whether dialysis will result in meaningful removal of letermovir from systemic circulation.

3 years.

This medicinal product does not require any special temperature storage conditions. Store in the original package in order to protect from moisture.

Packs of 28x1 tablets in Polyamide/Aluminium/PVC – Aluminium perforated unit dose blisters.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.