maribavir
Sources réglementaires consultées
Indications approuvées
- Traitement de l’infection ou maladie à CMV post-greffe résistante ou réfractaire à une ou plusieurs thérapies antérieures chez l’adulte.
Contre-indications
Absolues
- Hypersensibilité au maribavir ou aux excipients.
- Association au ganciclovir ou au valganciclovir.
Mises en garde cliniques
- Une résistance et un échec virologique peuvent survenir ; surveiller charge virale et génotype en cas de réponse insuffisante. — CIMA/AEMPS, ficha técnica 1221672002
Interactions médicamenteuses
- ModéréeGanciclovir ou valganciclovir
Mécanisme: Le maribavir antagonise l’activation de ces médicaments par pUL97.
Recommandation: Ne pas associer.
CIMA/AEMPS, ficha técnica 1221672002
- SévèreTacrolimus, ciclosporine, sirolimus ou évérolimus
Mécanisme: Le maribavir peut augmenter leurs concentrations.
Recommandation: Surveiller les concentrations et ajuster l’immunosuppresseur lors de l’instauration et de l’arrêt du maribavir.
CIMA/AEMPS, ficha técnica 1221672002
Effets indésirables
Communs (≥1%)
Trouble du goût, nausées, diarrhée et vomissements
Rares mais graves
Échec virologique et résistance du CMV
Grossesse et allaitement
Non recommandé pendant la grossesse ni chez les femmes en âge de procréer sans contraception efficace. Interrompre l’allaitement pendant le traitement.
Bibliographie récente (PubMed)
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433.
Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through the inhibition of UL97 protein kinase. In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up. The primary endpoint was confirmed cytomegalovirus clearance at end of week 8. The key secondary endpoint was achievement of cytomegalovirus clearance and symptom control at end of week 8, maintained through week 16. 352 patients were randomized (235 maribavir; 117 IAT). Significantly more patients in the maribavir versus IAT group achieved the primary endpoint (55.7% vs 23.9%; adjusted difference [95% confidence interval (CI)]: 32.8% [22.80-42.74]; P < .001) and key secondary endpoint (18.7% vs 10.3%; adjusted difference [95% CI]: 9.5% [2.02-16.88]; P = .01). Rates of treatment-emergent adverse events (TEAEs) were similar between groups (maribavir, 97.4%; IAT, 91.4%). Maribavir was associated with less acute kidney injury versus foscarnet (8.5% vs 21.3%) and neutropenia versus valganciclovir/ganciclovir (9.4% vs 33.9%). Fewer patients discontinued treatment due to TEAEs with maribavir (13.2%) than IAT (31.9%). One patient per group had fatal treatment-related TEAEs. Maribavir was superior to IAT for cytomegalovirus viremia clearance and viremia clearance plus symptom control maintained post-therapy in transplant recipients with R/R cytomegalovirus. Maribavir had fewer treatment discontinuations due to TEAEs than IAT. Clinical Trials Registration. NCT02931539 (SOLSTICE). Maribavir is an orally available, antiviral agent which inhibits the pUL97 kinase of cytomegalovirus (CMV) and is used to treat refractory forms of post-transplant C
Despite advances in monitoring and treatment, cytomegalovirus (CMV) infections remain one of the most common complications after solid organ transplantation (SOT). CMV infection may fail to respond to standard first- and second-line antiviral therapies with or without the presence of antiviral resistance to these therapies. This failure to respond after 14 days of appropriate treatment is referred to as "resistant/refractory CMV." Limited data on refractory CMV without antiviral resistance are available. Reported rates of resistant CMV are up to 18% in SOT recipients treated for CMV. Therapeutic options for treating these infections are limited due to the toxicity of the agent used or transplant-related complications. This is often the challenge with conventional agents such as ganciclovir, foscarnet and cidofovir. Recent introduction of new CMV agents including maribavir and letermovir as well as the use of adoptive T cell therapy may improve the outcome of these difficult-to-treat infections in SOT recipients. In this expert review, we focus on new treatment options for resistant/refractory CMV infection and disease in SOT recipients, with an emphasis on maribavir, letermovir, and adoptive T cell therapy.