Maribavir (Livtencity)
The Pharmacy and Therapeutics Committee approved the addition of Maribavir (Livtencity) to the inpatient formulary April 2022 with use restricted to the infectious diseases (ID) services. Maribavir is a first in class antiviral agent that inhibits CMV enzyme pUL97.
Efficacy
Maribavir is currently approved by the FDA for use in refractory CMV infection and disease in post-transplant patients.1-2 The current agent recommended for first line treatment of CMV is ganciclovir, but resistance to ganciclovir is increasingly becoming an issue.3Current guidelines recommend foscarnet or cidofovir as an agent in refractory or resistant CMV, but one of the more common gene mutations in UL97 is also resistant to foscarnet and cidofovir.3 As shown in the phase 2 and 3 studies outlined in Table 3, maribavir has shown superiority over regimens including valganciclovir, cidofovir, foscarnet, and ganciclovir for refractory CMV treatment in HSCT and SOT.4-7 In the phase 2 study done by Papanicolaou and colleagues, maribavir 400-1200 mg BID led to undetectable CMV viral load in 67% of patients by week 6 who had refractory CMV history.4-5 This was followed by the phase 3 study by Avery and colleagues that showed that maribavir 400 mg BID was superior to investigator assigned anti-CMV treatment (IAT) (valganciclovir, ganciclovir, foscarnet, or cidofovir) at 8 weeks for CMV DNA clearance.6-7
Safety
Maribavir has no contraindications or black box warnings against use in refractory CMV post-transplant patients.1 The main precaution for maribavir is the risk of reduced antiviral activity if used in combination with ganciclovir or valganciclovir and the potential for pUL97 resistance after maribavir use. Common side effects are dysgeusia, nausea, vomiting, diarrhea, and fatigue.
Uniqueness
Maribavir has a unique MOA, working by inhibiting protein kinase pUL97.1 Maribavir is a twice daily tablet that can be taken with or without meals for ease of use.1 There are fewer monitoring parameters for maribavir than valganciclovir, foscarnet, or ganciclovir.2 CMV DNA quantification is the main efficacy monitoring parameter required with use. For safety, monitoring is primarily needed for drug interactions. Patients receiving maribavir may be on immunosuppression, which will require levels to be drawn with initiation and dose changes of maribavir.2 Rates of neutropenia and acute kidney injury were low in studies and should only require routine monitoring in patients that have myelosuppression or chronic kidney disease at baseline.4-12 Overall, maribavir is an efficacious option for refractory CMV that is easy to administer and monitor both inpatient and outpatient.