Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands
PREVYMIS is indicated for prophylaxis of cytomegalovirus (CMV) reactivation and disease in adult and paediatric patients weighing at least 5 kg who are CMV-seropositive recipients [R+] of an allogeneic haematopoietic stem cell transplant (HSCT).
PREVYMIS is indicated for prophylaxis of CMV disease in CMV-seronegative adult and paediatric patients weighing at least 40 kg who have received a kidney transplant from a CMV-seropositive donor [D+/R-].
Consideration should be given to official guidance on the appropriate use of antiviral agents.
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.
Letermovir is also available for oral administration (240 mg and 480 mg film-coated tablets, and 20 mg and 120 mg granules in sachet).
Letermovir tablets, granules in sachet, and concentrate for solution for infusion may be used interchangeably at the discretion of the physician. Dose adjustm ent 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 film-coated tablets or letermovir granules in sachet for dosing information.
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 i n clinical trials.
The recommended dose of letermovir is 480 mg once daily.
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).
The recommended doses of letermovir for paediatric patients weighing less than 30 kg are shown in Table 1 (see also section 5.2). Letermovir should be administered once daily.
If intravenous letermovir is co-administered with cyclosporine, the dose of letermovir does not require adjustment as shown in Table 1 (see also sections 4.5 and 5.2).
Table 1. Recommended dose of letermovir concentrate for solution for infusion without or with cyclosporine in paediatric patients weighing less than 30 kg:
| Body weight | Daily intravenous dose without or with cyclosporine |
|---|---|
| 15 kg to less than 30 kg | 120 mg |
| 7.5 kg to less than 15 kg | 60 mg |
| 5 kg to less than 7.5 kg | 40 mg |
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.
The recommended dose of letermovir is 480 mg once daily.
recipients If letermovir is co-administered with cyclosporine, the dose of letermovir should be dec reased to 240 mg once daily (see sections 4.5 and 5.2).
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.
No dose adjustment of letermovir is required based on age (see sections 5.1 and 5.2).
No dose adjustment of letermovir is required based on mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) hepatic impairment. Letermovir is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment (see section 5.2).
Letermovir is not recommended in patients with moderate hepatic impairment combined with moderate or severe renal impairment (see section 5.2).
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 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 (see sections 4.4 and 5.3). In patients with moderate or severe renal impairment (creatinine clearance less than 50 mL/min), or in young children (less than 2 years of age) receiving PREVYMIS, accumulation of hydroxypropylbetadex could occur. Serum creatinine levels should be closely monitored in these patients.
If possible, intravenous administration should not exceed 4 weeks.
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 supp orted by pharmacokinetic/pharmacodynamic extrapolation.
For intravenous use only.
Letermovir concentrate for solution for infusion requires dilution (see section 6.6) prior to administration.
Letermovir diluted solution must be administered through a sterile 0.2 micron or 0.22 micron polyethersulfone (PES) in-line filter. Do not administer the diluted solution through a filter other than a sterile 0.2 micron or 0.22 micron PES in-line filter.
Letermovir should be administered as an intravenous infusion only.
After dilution, letermovir 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 intravenous bag should be administered.
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.
Unopened vial: 3 years.
After opening: Use immediately.
Storage of diluted solution:
Chemical and physical in-use stability has been demonstrated for 48 hours at 25°C and for 48 hours at 2 to 8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
This medicinal product does not require any special temperature storage conditions.
Store in original carton to protect from light.
For storage conditions after dilution of the medicinal product, see section 6.3.
Type I (30 mL) clear glass vial with a 20 mm fluorocoated chlorobutyl stopper with aluminium flip-off cap containing 12 mL (medium green cap) or 24 mL (dark blue cap) of solution.
Pack size: 1 vial.
PREVYMIS vials are for single use only.
PREVYMIS concentrate for solution for infusion must be diluted prior to intravenous use.
Inspect vial contents for discolouration and particulate matter prior to dilution. PREVYMIS concentrate for solution for infusion is a clear, colourless solution and may contain a few product-related small translucent or white particles. Do not use the vial if the solution is cloudy, discoloured or contains matter other than a few small translucent or white particles.
Do not use PREVYMIS concentrate for solution for infusion with intravenous bags and infusion set materials containing polyurethane or the plasticizer diethylhexyl phthalate (DEHP). Materials that are phthalate-free are also DEHP-free.
Do not shake PREVYMIS vial.
For the 480 mg or 240 mg dose, add one single-dose vial (either 12 mL (240 mg dose) or 24 mL (480 mg dose)) of PREVYMIS concentrate for solution for infusion to a 250 mL pre-filled intravenous bag containing either sodium chloride 9 mg/mL (0.9%) solution for injection or 5% dextrose, and mix the diluted solution by gentle inversion. Do not shake. If a vial is added to a 250 mL intravenous diluent bag, the final concentration ranges of letermovir would be 0.9 mg/mL (for 240 mg dose) and 1.8 mg/mL (for 480 mg dose).
For the 120 mg or 60 mg dose, prepare PREVYMIS concentrate for solution for infusion according to Table 11 below in sodium chloride 9 mg/mL (0.9%) solution for injection or 5% dextrose, and mix the diluted solution by gentle inversion. Do not shake.
For the 40 mg dose, prepare PREVYMIS concentrate for solution for infusion according to Table 12 below in either sodium chloride 9 mg/mL (0.9%) solution for injection or 5% dextrose, and mix the diluted solution by gentle inversion. Do not shake.
Table 11. Preparation of PREVYMIS intravenous solution for doses of 120 mg or 60 mg:
| Intravenous dose | Volume of 20 mg/mL PREVYMIS concentrate for solution for infusion | Final infusion volume | Final concentration of letermovir |
|---|---|---|---|
| 120 mg | 6 mL of 20 mg/mL | 75 mL | 1.6 mg/mL |
| 60 mg | 3 mL of 20 mg/mL | 50 mL | 1.2 mg/mL |
Table 12. Preparation of PREVYMIS intravenous solution for a dose of 40 mg:
| Intravenous dose | Volume of 2 mg/mL PREVYMIS dilution (1:10)* | Final infusion volume | Final concentration of letermovir |
|---|---|---|---|
| 40 mg | 20 mL of 2 mg/mL | 20 mL | 2 mg/mL |
* To prepare 2 mg/mL PREVYMIS dilution, add 5 mL of 20 mg/mL PREVYMIS concentrate for solution for infusion from the vial to 45 mL of diluent (sodium chloride 9 mg/mL (0.9%) solution for injection or 5% dextrose) and mix gently.
Once diluted, the solution of PREVYMIS is clear, and ranges from colourless to yellow. Variations of colour within this range do not affect the quality of the product. The diluted solution should be inspected visually for particulate matter and discolouration prior to administration. Discard if the diluted solution is cloudy, discoloured or contains matter other than a few small translucent or white particles.
See section 4.2.
PREVYMIS diluted solution must be administered through a sterile 0.2 micron or 0.22 micron polyethersulfone (PES) in-line filter.
PREVYMIS concentrate for solution for infusion is compatible with 0.9% sodium chloride and 5% dextrose solutions.
PREVYMIS should not be co-administered through the same intravenous line (or cannula) with other medicinal products and diluent combinations except those listed below.
List of compatible medicinal products when PREVYMIS and medicinal products* are prepared in 0.9% sodium chloride:
* Refer to the prescribing information to confirm compatibility of simultaneous co-administration.
List of compatible medicinal products when PREVYMIS and medicinal products* are prepared in 5% dextrose:
* Refer to the prescribing information to confirm compatibility of simultaneous co-administration.
† Amphotericin B (lipid complex) is compatible with PREVYMIS. However, Amphotericin B (liposomal) is incompatible (see section 6.2).
PREVYMIS is compatible with the following intravenous bags and infusion set materials. Any intravenous bags or infusion set materials not listed below should not be used.
Intravenous bag materials: Polyvinyl chloride (PVC), ethylene vinyl acetate (EVA) and polyolefin (polypropylene and polyethylene)
Infusion set materials: PVC, polyethylene (PE), polybutadiene (PBD), silicone rubber (SR), styrene–butadiene copolymer (SBC), styrene-butadiene-styrene copolymer (SBS), polystyrene (PS)
Plasticizers: Tris (2-ethylhexyl) trimellitate (TOTM), butyl benzyl phthalate (BBP)
Catheters: Radiopaque polyurethane
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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