Pediatric HSCT Indication
Pediatric HSCT Indication
Therapeutic indications1
PREVYMIS® is indicated for prophylaxis of cytomegalovirus (CMV) reactivation and disease in adult and pediatric patients weighing at least 15 kg who are CMV-seropositive recipients (R+) of an allogeneic haematopoietic stem cell transplant (allo-HSCT).
Posology and method of administration1
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 pediatric 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. The safety and efficacy of letermovir use for more than 200 days has not been studied in clinical trials.
Pediatric patients weighing at least 15 kg to less than 30 kg who are HSCT recipients
The recommended dose of letermovir granules is 240 mg once daily that can be administered as one 240 mg tablet. The granules may not be available in your country.
The recommended intravenous doses of letermovir for paediatric patients weighing less than 30 kg are:
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
For pediatric patients who cannot swallow tablets, refer to the prescribing information for letermovir granules in sachet for dosing information.
The granules may not be available in your country.
Dose adjustment in pediatric 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. 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.
Adverse reactions1
The safety assessment of letermovir in pediatric 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. Their age distribution was as follows:
28
adolescents
14
children aged 7 to less than 12 years
13
aged 2 to less than 7 years
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.
Clinical efficacy and safety1
P030: Pediatric recipients of an allogeneic hematopoietic stem cell transplant
To evaluate letermovir prophylaxis as a preventive strategy for CMV infection or disease in pediatric transplant recipients, the efficacy of letermovir was assessed in a multicentre, open-label, single-arm Phase 2b trial (P030) in pediatric recipients of an allogeneic HSCT. Study drug was initiated after HSCT (Day 0-28 post-HSCT) and continued through Week 14 post-HSCT. Study drug was administered either orally or intravenously; the dose of letermovir was based on age, body weight and formulation.
Among the 63 treated subjects, 8 were 0 to less than 2 years of age, 27 were 2 to less than 12 years of age and 28 were 12 to less than 18 years of age. At baseline, 87% of subjects received a myeloablative regimen, 67% were receiving cyclosporine, and 27% were receiving tacrolimus. The most common primary reasons for transplant were acute myeloid leukaemia (18%) and aplastic anaemia (10%) in the overall population, and combined immunodeficiency (37.5%) and familial haemophagocytic lymphohistiocytosis (25.0%) in children less than 2 years of age.
Secondary efficacy endpoint
The efficacy endpoints of P030 were secondary and included the incidence of clinically significant CMV infection through Week 14 post-HSCT and through Week 24 post-HSCT. Clinically significant CMV infection was defined as the occurrence of either CMV end-organ disease, or initiation of anti-CMV PET based on documented CMV viremia and the clinical condition of the subject. The incidence of clinically significant CMV infection was 7.1% and 10.7% through Week 14 post-HSCT and Week 24 post-HSCT, respectively.
Pharmacokinetic properties1
In healthy adult subjects, the pharmacokinetics of letermovir have been characterised following oral and intravenous administration. Letermovir exposure increased in a greater than dose-proportional manner with both oral or intravenous administration. The mechanism is likely saturation/autoinhibition of OATP1B1/3.
Letermovir AUC in pediatric HSCT recipients was estimated via population pharmacokinetic analysis using observed PK data from study P030 (see Table 1 and Table 2). Exposures for pediatric HSCT recipients across body weight bands are within the range of exposures achieved in the adult HSCT reference exposures.
Table 1: Letermovir AUC (ng•hr/mL) values following oral administration in paediatric HSCT recipients
Body weight
Oral dose, no cyclosporine
Median (90% prediction interval)*
Oral dose, with cyclosporine
Median (90% prediction interval)*
30 kg and above
480 mg
39 100
(18 700-81 300)
240 mg
49 100
(23 200-104 000)
15 kg to less than 30 kg
240 mg
38 900
(20 200-74 300)
120 mg
51 000
(26 600-98 200)
7.5 kg to less than 15 kg
120 mg
32 000
(16 700-59 300)
60 mg
41 600
(22 300-81 100)
5 kg to less than 7.5 kg
80 mg
30 600
(16 200-55 000)
40 mg
39 000
(20 600-72 000)
*Medians and 90% prediction intervals are based on simulations using the paediatric HSCT population PK model with inter-individual variability.
Table 2: Letermovir AUC (ng•hr/mL) values following intravenous administration in paediatric HSCT recipients
Body weight
Intravenous dose, no cyclosporine
Median (90% prediction interval)*
Intravenous dose, with cyclosporine
Median (90% prediction interval)*
30 kg and above
480 mg
111 000
(55 700-218 000)
240 mg
59 800
(28 400-120 000)
15 kg to less than 30 kg
120 mg
57 200
(29 700-113 000)
120 mg
61 100
(29 900-121 000)
7.5 kg to less than 15 kg
60 mg
46 000
(24 300-83 900)
60 mg
49 200
(25 800-93 800)
5 kg to less than 7.5 kg
40 mg
43 400
(24 300-81 000)
40 mg
45 900
(24 900-82 200)
*Medians and 90% prediction intervals are based on simulations using the paediatric HSCT population PK model with inter-individual variability.
References:
- PREVYMIS®. Summary of product characteristics, April 2025.
PREVYMIS (letermovir) direkt verkande virushämmande medel (Rx, Subventioneras, SPC 04/2025) filmdragerade tabletter 240 mg och 480 mg, koncentrat till infusionsvätska/lösning 240 mg.
Terapeutiska indikationer: PREVYMIS är avsett som profylax mot reaktivering av cytomegalovirus (CMV) och CMV-sjukdom hos vuxna och pediatriska patienter som väger minst 15 kg som är CMV-seropositiva mottagare [R+] av en allogen hematopoetisk stamcellstransplantation (HSCT).
PREVYMIS är avsett som profylax mot CMV-sjukdom hos CMV-seronegativa vuxna och pediatriska patienter som väger minst 40 kg som har genomgått en njurtransplantation från en CMV-seropositiv donator [D+/R-].
Officiella riktlinjer för korrekt användning av virushämmande medel bör beaktas.
Kontraindikationer: Överkänslighet mot den aktiva substansen eller mot något hjälpämne. Samtidig administrering med pimozid, johannesört (Hypericum perforatum) och/eller med ergotalkaloider. När letermovir kombineras med ciklosporin är samtidig användning av dabigatran, atorvastatin, simvastatin, rosuvastatin eller pitavastatin kontraindicerat.
Varningar och försiktighet:
Monitorering av CMV-DNA: I studier avbröts profylax med letermovir och preemptiv standardbehandling (PET) påbörjades vid kliniskt signifikant CMV-DNAemi eller sjukdom. För patienter där profylax med letermovir påbörjades och för vilka test av CMV-DNA vid baseline senare visade sig vara positivt, kunde profylaktisk behandling fortsätta om kriterierna för PET inte hade uppfyllts.
Risk för biverkningar eller sämre behandlingseffekt på grund av läkemedelsinteraktioner: Samtidig användning av letermovir och vissa läkemedel kan orsaka kända eller potentiellt signifikanta läkemedelsinteraktioner, av vilka några kan leda till:
• eventuellt kliniskt signifikanta biverkningar på grund av högre exponering för samtidiga läkemedel eller för letermovir.
• signifikant lägre plasmakoncentration av det samtidiga läkemedlet, vilket kan leda till sämre behandlingseffekt av det samtidiga läkemedlet.
Se tabell 1 i SPC för information om åtgärder för att förhindra eller hantera dessa kända eller potentiellt signifikanta interaktioner, inklusive doseringsrekommendationer.
Letermovir ska användas med försiktighet tillsammans med läkemedel som är CYP3A‑substrat med snävt terapeutiskt intervall. Noggrann monitorering och/eller dosjustering av samtidigt administrerade CYP3A‑substrat rekommenderas. Ökad monitorering av ciklosporin, takrolimus och sirolimus rekommenderas generellt de två första veckorna efter att letermovir har påbörjats och avslutats (se avsnitt 4.5 i SPCn) såväl som efter förändring av administreringssättet av letermovir.
Graviditet
Letermovir rekommenderas inte under graviditet och till fertila kvinnor som inte använder preventivmedel.
Amning
Det är okänt om letermovir utsöndras i bröstmjölk. Ett beslut måste fattas om man ska avbryta amningen eller avbryta/avstå från behandling med letermovir efter att man tagit hänsyn till fördelen med amning för barnet och fördelen med behandling för kvinnan.
För fullständig information, priser och förpackningar, se www.fass.se
SE-CYT-00033, 04/2025.
