DRUG INTERACTIONS-(summary)-­ 

 • Coadministration with strong CYP3A4 inducers: not recommended. Refer to full prescribing information for dosage modification when coadministered with certain anticonvulsants. 

BRIEF SUMMARY

MARIBAVIR- (Nov 2021)

Indn-  To treat PostTransition Clitomegalovirus (CMV) Infection /Disease that does nor respond (or without Genetic Mutation that cause resistence) to available Antiviral Treatment for CMV 

Comp-   Tablets: 200 mg of maribavir. 400 mg (two 200 mg tablets) orally twice daily with or without food. 

ADR-  The most common adverse events (all grades, >10%) in subjects treated with  were taste disturbance, nausea, diarrhea, vomiting, and fatigue.

 WARNINGS AND PRECAUTIONS-

­ •  may antagonize the antiviral activity of ganciclovir and valganciclovir. Coadministration is not recommended.

 • Virologic failure can occur during and after treatment . Monitor CMV DNA levels and check for resistance if patient does not respond to treatment.r.

Pat Inform

nform patients that LIVTENCITY may interact with other drugs. Advise patients to report to their healthcare provider the use of any other medication

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U.S. FDA APPROVED DRUGS SURING 2021                                        

Serial No 46

Name of the Drug-    LIVTENCITY

Active Ingredient -   Maribavir

Pharmacological Classification- To treat PostTransition Clitomegalovirus (CMV)                                                               Infection /Disease that does nor respond (or                                                                   without Genetic Mutation that cause resistence)                                                             to available Antiviral Treatment for CMV                                                                                                                                                                                                                                                                                                               Date of Approval-          11/23/21 

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use                                  LIVTENCITY safely and effectively.                                                                                See full prescribing information for LIVTENCITY LIVTENCITY (maribavir) tablets, for oral use

Initial U.S. Approval: 2021

 INDICATIONS AND USAGE-

­ LIVTENCITY is a cytomegalovirus (CMV) pUL97 kinase inhibitor indicated for the treatment of adults and pediatric patients (12 years of age and older and weighing at least 35 kg) with post-transplant CMV infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir or foscarnet.

DOSAGE AND ADMINISTRATION-

­ 400 mg (two 200 mg tablets) orally twice daily with or without food. 

 DOSAGE FORMS AND STRENGTHS-

­ Tablets: 200 mg of maribavir. 

PATIENT COUNSELING INFORMATION-

Advise the patient to read the FDA-approved patient labeling (Patient Information). 

Inform patients that LIVTENCITY may interact with other drugs.

Advise patients to report to their healthcare provider the use of any other medication

Distributed by: Takeda Pharmaceuticals America, Inc. Lexington, MA 02421 LIVTENCITY™ and the LIVTENCITY™ logo are trademarks or registered trademarks of Takeda Pharmaceuticals International AG. TAKEDA® and the TAKEDA Logo® are registered trademarks of Takeda Pharmaceutical Company Limited. ©2021 Takeda Pharmaceuticals U.S.A., Inc. All rights reserved. MAR358

CLINICAL PHARMACOLOGY-

1. Mechanism of Action-                                                                                         LIVTENCITY is an antiviral drug against human CMV [see Microbiology (12.4)].

2. Pharmacodynamics-                                                                                               Exposure-response In dose-ranging studies that evaluated doses of 400 mg twice daily and twice daily doses of two and three times the recommended dose, no exposure-response relationship was observed for viral load or probability of unquantifiable plasma CMV DNA.

Cardiac Electrophysiology-                                                                                             At three times the recommended dose (approximately twice the peak concentration observed following the recommended dose), LIVTENCITY does not prolong the QT interval to any clinically relevant extent

.3. Pharmacokinetics-                                                                                             LIVTENCITY pharmacological activity is due to the parent drug.                                        Following oral administration, plasma maribavir exposure (Cmax and AUC) increased approximately dose-proportionally following a single dose of 50 to 1600 mg (0.125 to four times the recommended dose) and multiple doses up to 2400 mg per day (three times the recommended daily dose).

Maribavir PK is time-independent. With twice-daily dosing, steady state is reached within 2 days, with mean accumulation ratios of Cmax and AUC ranging from 1.37 to 1.47. The pharmacokinetic properties of maribavir following administration of LIVTENCITY are displayed in Table 4

Distribution- Mean apparent steady-state volume of distribution (Vss, L) 27.3 % bound to human plasma proteins 98.0 across the concentration range of 0.05-200 µg/mL Blood-to plasma ratio 1.37

Elimination -                                                                                                                Major route of elimination Hepatic metabolism Half-life (t1/2) in transplant patients (h), mean 4.32 Oral clearance (CL/F) in transplant patients (L/h), mean 2.85 Metabolism Metabolic pathwaysb CYP3A4 (major) and CYP1A2 (minor)

Excretion % of dose excreted as total 14C (unchanged drug) in urinec 61 (<2) % of dose excreted as total 14C (unchanged drug) in fecesc 14 (5.7)

Specific Populations -                                                                                                 There were no clinically significant differences in the pharmacokinetics of maribavir based on age (18-79 years), gender, race (Caucasian, Black, Asian, or others), ethnicity (Hispanic/Latino or non-Hispanic/Latino),

Pediatric Patients The pharmacokinetics of maribavir in patients less than 18 years of age have not been evaluated.

USE IN SPECIFIC POPULATIONS-

1. Pregnancy Risk Summary-

No adequate human data are available to establish whether LIVTENCITY poses a risk to pregnancy outcomes.

The background risk of major birth defects and miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

2. Lactation Risk Summary-

It is not known whether maribavir or its metabolites are present in human or animal milk, affect milk production, or have effects on the breastfed infant.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LIVTENCITY and any potential adverse effects to the breast-fed child.

3.Pediatric Use-                                                                                                              The recommended dosing regimen in pediatric patients 12 years of age and older and weighing at least 35 kg is the same as that in adults.

Use of LIVTENCITY in this age group is based on the following:                                         • Evidence from controlled studies of LIVTENCITY in adults

• Population pharmacokinetic (PK) modeling and simulation demonstrating that age and body weight had no clinically meaningful effect on plasma exposures of LIVTENCITY

• LIVTENCITY exposure is expected to be similar between adults and children 12 years of age and older and weighing at least 35 kg

• The course of the disease is similar between adults and pediatric patients to allow extrapolation of data in adults to pediatric patients

 The safety and effectiveness of LIVTENCITY have not been established in children younger than 12 years of age.

4. Geriatric Use-                                                                                                              No dosage adjustment is required for patients over 65 years of age based on the results from population pharmacokinetics analysis [see Clinical Pharmacology (12.3)] and efficacy and safety data from the clinical studies. In the clinical Study 303, 54 patients aged 65 years and over were treated with LIVTENCITY. Safety, effectiveness, and pharmacokinetics were consistent between elderly patients (=65 years) and younger patients (<65 years).

5. Impaired Renal Function -                                                                                           No dose adjustment of LIVTENCITY is needed for patients with mild, moderate, or severe renal impairment

 Administration of LIVTENCITY in patients with end stage renal disease (ESRD), including patients on dialysis, has not been studied.

6. Impaired Hepatic Function-                                                                                        No dose adjustment of LIVTENCITY is needed for patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment

. Administration of LIVTENCITY in patients with severe hepatic impairment has not been studied. 10

OVERDOSAGE-

There is no known specific antidote for LIVTENCITY. In case of overdose, it is recommended that the patient be monitored for adverse reactions and appropriate symptomatic treatment instituted.

Due to the high plasma protein binding of LIVTENCITY, dialysis is unlikely to reduce plasma concentrations of LIVTENCITY significantly.