Livtencity (maribavir) dosing, indications, interactions, adverse effects, and more (original) (raw)
Dosing & Uses
AdultPediatric
Dosage Forms & Strengths
tablet
- 200mg
Cytomegalovirus Infection
Indicated for treatment of posttransplant CMV infection/disease that is refractory to treatment with or without genotypic resistance (eg, ganciclovir, valganciclovir, cidofovir, foscarnet) in adults and pediatric patients aged ≥12 years who weigh ≥35 kg
400 mg PO BID with or without food
Dosage Modifications
Coadministration with anticonvulsants
- Coadministered with carbamazepine: Increase dose to 800 mg PO BID
- Coadministered with phenytoin or phenobarbital: Increase dosage to 1,200 mg PO BID
Renal impairment
- Mild-to-severe (CrCl 12-70 mL/min): No dosage adjustment necessary
- End-stage renal disease: Not studied
Hepatic impairment
- Mild-to-moderate (Child-Pugh A or B): No dosage adjustment necessary
- Severe (Child-Pugh C): Not studied
Dosage Forms & Strengths
tablet
- 200mg
Cytomegalovirus Infection
Indicated for treatment of posttransplant CMV infection/disease that is refractory to treatment with or without genotypic resistance (eg, ganciclovir, valganciclovir, cidofovir, foscarnet) in adults and pediatric patients aged ≥12 years who weigh ≥35 kg
400 mg PO BID with or without food
Dosage Modifications
Coadministration with anticonvulsants
- Coadministered with carbamazepine: Increase dose to 800 mg PO BID
- Coadministered with phenytoin or phenobarbital: Increase dosage to 1,200 mg PO BID
Renal impairment
- Mild-to-severe (CrCl 12-70 mL/min): No dosage adjustment necessary
- End-stage renal disease: Not studied
Hepatic impairment
- Mild-to-moderate (Child-Pugh A or B): No dosage adjustment necessary
- Severe (Child-Pugh C): Not studied
Adverse Effects
>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%)
Warnings
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 & Lactation
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.
Pharmacology
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%])
Administration
Oral Administration
Take with or without food
Storage
Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
Images
No images available for this drug.
Patient Handout
A Patient Handout is not currently available for this monograph.
Formulary
FormularyPatient Discounts
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View explanations for tiers and restrictions
| Tier | Description |
|---|---|
| 1 | This drug is available at the lowest co-pay. Most commonly, these are generic drugs. |
| 2 | This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. |
| 3 | This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. |
| 4 | This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. |
| 5 | This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. |
| 6 | This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. |
| NC | NOT COVERED – Drugs that are not covered by the plan. |
| Code | Definition |
|---|---|
| PA | Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. |
| QL | Quantity Limits Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered. |
| ST | Step Therapy Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription. |
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.