maribavir (Rx)

>10%

*Denotes incidence slightly less than investigator-assigned treatment that was compared with maribavir

Taste disturbance (46%)

Creatinine ≥1.5 to <2.5 mg/dL (33%)

Hemoglobin ≥8 to <9.5 g/dL (32%)

Nausea (21%)*

Diarrhea (19%)*

Platelet cell count ≥50,000 to <100,000 cells/µL (18%)

Hemoglobin ≥6.5 to <8 g/dL (15%)

Vomiting (14%)*

Fatigue (12%)

Platelet cell count ≥25,000 to <50,000 cells/µL (12%)

1-10%

Creatinine >2.5 mg/dL (7%)

Platelet cell count <25,000 cells/µL (5%)

Neutrophils ≥750 to <1,000 cells/µL (4%)

Neutrophils ≥500 to <750 cells/µL (3%)

Neutrophils <500 cells/µL (2%)

Hemoglobin <6.5 g/dL (1%)

Contraindications

None

Cautions

Virologic failure during treatment and relapse post-treatment

• Virologic failure due to resistance can occur during and after treatment
• Virologic relapse during posttreatment period usually occurred within 4-8 weeks after treatment discontinuation
• Monitor CMV DNA levels and check for maribavir resistance if nonresponsive to treatment or relapses occurs

Drug interaction overview

• Substrate of CYP3A4; weak inhibitor of CYP3A4, P-gp, and BCRP

• Strong CYP3A4 inducers (anticonvulsants)

  • Increase maribavir dose
  • Strong CYP3A4 inducers (eg, phenytoin, phenobarbital, carbamazepine) decrease maribavir plasma concentration and may result in reduced virologic response

• Strong CYP3A4 inducers (other)

  • Not recommended
  • Strong CYP3A4 inducers (eg, rifabutin, rifampin, St. John’s wort) decrease maribavir plasma concentration and may result in reduced virologic response

• Valganciclovir and ganciclovir

  • Not recommended
  • Maribavir may antagonize antiviral activity of ganciclovir and valganciclovir by inhibiting human CMV pUL97 kinase, which is required for activation/phosphorylation of ganciclovir and valganciclovir

• Immunosuppressants

  • Frequently monitor immunosuppressant drug levels during treatment, especially following initiation and after discontinuation and adjust immunosuppressant dose, as needed
  • Maribavir may increase concentrations of immunosuppressive drugs that are CYP3A4 and P-gp substrates (eg, tacrolimus, everolimus, sirolimus, cyclosporine) where minimal concentration changes may lead to serious adverse effects

• Digoxin

  • Use with caution; monitor digoxin levels; digoxin dose may need to be reduced
  • Maribavir may increase digoxin levels by inhibiting P-gp

• Rosuvastatin

  • Closely monitor for rosuvastatin-related events (eg, myopathy, rhabdomyolysis)
  • Maribavir may increase rosuvastatin levels

Pregnancy

No adequate human data are available to establish drug-related risks to pregnancy outcomes

Animal data

• Embryofetal survival was decreased in rats at maribavir exposures less than those observed in humans at the recommended human dose (RHD)
• Decreased number of viable fetuses and increase in early resorptions and post-implantation losses were observed at ≥100 mg/kg/day (at exposures approximately half the human exposure at the RHD)
• Intermittent reduced body weight gain was observed in pregnant animals at ≥200 mg/kg/day

Lactation

Unknown whether maribavir or its metabolites are present in human or animal milk, its effects on milk production, or its effect on breastfed infants

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Antiviral activity mediated by competitive inhibition of the protein kinase activity of human CMV enzyme pUL97, which inhibits protein phosphorylation

Maribavir inhibited human CMV replication in virus yield reduction, DNA hybridization, and plaque reduction assays in human lung fibroblast cell line, human embryonic kidney, and human foreskin fibroblast cells

Absorption

Peak plasma time: 1-3 hr

AUC: 128 µg·hr/mL

Peak plasma concentration: 17.2 µg·hr/mL

Distribution

Vd (steady-state): 27.3 L

Plasma bound: 98%

Blood-to-plasma ratio: 1.37

Metabolism

Metabolized by CYP3A4 (major) and CYP1A2 minor

Elimination

Clearance: 2.85 L/hr

Half-life: 4.32 hr

Excretion: Urine (61% [<2% unchanged]); feces (14% [5.7%])

Oral Administration

Take with or without food

Storage

Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)