Livtencity Maribavir Tablets

1. Indications and Usage
Treatment of Refractory Cytomegalovirus (CMV) Infection/Disease:
Indicated for the treatment of adults and pediatric patients (12 years of age and older and weighing at least 35 kg) with refractory (with or without genotype-resistance) CMV infection/disease following allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), who have failed to respond to one or more prior anti-CMV therapies, including ganciclovir, valganciclovir, cidofovir, or foscarnet.
2. Dosage and Administration
Recommended Dosage:
Adults and Pediatric Patients (≥12 years and ≥35 kg): 400 mg (two 200 mg tablets) orally twice daily.
Administration Instructions:
Can be taken with or without food.
Tablets can be swallowed whole, dispersed in water, or crushed and administered orally or via nasogastric (NG) or orogastric (OG) tubes.
Dosage Adjustments with Anticonvulsants:
Carbamazepine: Increase dosage to 800 mg twice daily.
Phenytoin or Phenobarbital: Increase dosage to 1200 mg twice daily.
Missed Dose:
If a dose is missed, it should be taken as soon as possible unless it is within 3 hours of the next scheduled dose. Do not double the dose.
3. Mechanism of Action
CMV pUL97 Kinase Inhibitor:
Maribavir is an antiviral agent that specifically inhibits the human cytomegalovirus (CMV) pUL97 protein kinase.
Physiological Effect:
Inhibition of pUL97 blocks viral replication and the nuclear egress of viral capsids. It acts independently of viral DNA polymerase, making it effective against many ganciclovir-resistant strains.
4. Safety and Warnings
Antiviral Activity Reduction with Ganciclovir/Valganciclovir:
Maribavir may antagonize the antiviral activity of ganciclovir and valganciclovir by inhibiting the pUL97 kinase required for their phosphorylation. Concomitant use is not recommended.
Treatment Failure and Viral Recurrence:
Treatment failure due to resistance may occur. Viral recurrence typically happens within 4-8 weeks after stopping treatment. Monitoring of CMV DNA levels is required.
Drug Interactions:
Immunosuppressants: Maribavir may increase concentrations of CYP3A4 and/or P-gp substrate immunosuppressants (e.g., tacrolimus, cyclosporine). Frequent monitoring and dose adjustments are necessary.
CYP3A Inducers: Concomitant use with strong CYP3A inducers (e.g., rifampin) is not recommended as it may decrease maribavir efficacy.
5. Adverse Reactions
Most Common:
Dysgeusia (altered taste), nausea, diarrhea, vomiting, and fatigue.
Laboratory Abnormalities:
Neutropenia, anemia, thrombocytopenia, and elevated creatinine.
6. Drug Interactions
Substrates of CYP3A and P-gp:
Maribavir is an inhibitor of CYP3A and P-gp. Co-administration with substrates (e.g., tacrolimus, sirolimus) requires therapeutic drug monitoring.
P-gp Inducers:
(e.g., Rifampin, St. John’s wort) May significantly decrease maribavir plasma concentrations.
7. Pharmaceutical Information
Chemical Name:
(2S,3S,4R,5S)-2-(5,6-dichloro-2-(isopropylamino)-1H-benzo[d]imidazol-1-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol