Identification
- Summary
Maribavir is a cytomegalovirus (CMV) pUL97 kinase inhibitor used for the treatment of refractory post-transplant CMV infection.
- Brand Names
- Livtencity
- Generic Name
- Maribavir
- DrugBank Accession Number
- DB06234
- Background
Maribavir is an inhibitor of the cytomegalovirus (CMV; HHV5) pUL97 kinase which is used to treat CMV infections in patients post-transplantation.5 Most standard CMV therapies, such as ganciclovir or foscarnet, target CMV DNA polymerase - while generally effective, these medications tend to promote the development of CMV resistance to DNA polymerase-based therapies, and their use is often limited by toxicities like myelosuppression and renal injury.4 Maribavir is novel in that it instead targets the CMV pUL97 kinase, thereby providing an effective alternative treatment option in cases of resistant infections.
Maribavir was approved by the FDA in November 2021, under the name Livtencity (Takeda), for the treatment of resistant CMV infections in post-transplant patients.6 The drug was also approved by Health Canada in September 2022 7 and by European Commission in November 2022.9
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Maribavir (DB06234)
- Weight
- Average: 376.23
Monoisotopic: 375.0752615 - Chemical Formula
- C15H19Cl2N3O4
- Synonyms
- Maribavir
- External IDs
- 1263-W-94
- 1263W94
Pharmacology
- Indication
Maribavir is indicated for the treatment of post-transplant cytomegalovirus (CMV) infection (following hematopoietic stem cell transplant or solid organ transplant) which is refractory to standard treatment with ganciclovir, valganciclovir, cidofovir, or foscarnet.5,7,8
In the US, patients receiving the treatment should weigh more than 35 kg and be at least 12 years old.5 In Canada and Europe, maribavir is only approved in adults.7,8
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Post-transplant cytomegalovirus (cmv) infection •••••••••••• ••••• •••••••••• •• •••••••• ••••••••• •••••• Treatment of Post-transplant cytomegalovirus (cmv) infection •••••••••••• •••••••••• •• •••••••• •••••••••• •••••• •• ••••• •• •• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Maribavir exerts its antiviral efficacy via an alternative target as compared to traditional CMV antivirals and is thus useful in the treatment of CMV infections that have proven resistant to standard therapy.6
Maribavir should not be used concomitantly with ganciclovir or valganciclovir, as these molecules both require activation via CMV pUL97 in order to exert their antiviral effect. Taking them alongside maribavir - an inhibitor of this same kinase - will therefore significantly reduce their antiviral activity.5
- Mechanism of action
Human cytomegalovirus (CMV) is a herpesvirus commonly causing infection in patients following stem cell or organ transplants.6 As with other herpesviruses, CMV tends to persist in the host and become reactivated under immunosuppressive conditions3 - patients requiring multiple immunosuppressive medications to combat transplant rejection are thus at a much higher risk of developing serious CMV infections.3,6
Maribavir belongs to a class of anti-cytomegalovirus antivirals called benzimidazole ribosides.3 It competitively inhibits the human CMV pUL97 viral protein kinase, which results in viable but severely defective viruses upon replication,4 although the reasons for this remain poorly defined. In addition, maribavir also inhibits viral release from the nucleus to the cytoplasm by inhibiting pUL97-dependent phosphorylation of the nuclear lamina component lamin A/C, although the extent to which this activity contributes to its antiviral efficacy is unclear.4
Target Actions Organism ASerine/threonine protein kinase UL97 inhibitorHHV-5 - Absorption
Population pharmacokinetic modeling in patients receiving maribavir 400mg twice daily showed an AUC0-tau and Cmax of 128 µg.h/mL and 17.2 µg/mL, respectively.5 It has a median Tmax of one to three hours.5
- Volume of distribution
The mean apparent steady-state volume of distribution for maribavir was 27.3 L.5
- Protein binding
Across all concentration ranges tested, maribavir was extensively (~98%) protein-bound in plasma,5 likely primarily to serum albumin and alpha-1-acid glycoprotein.3
- Metabolism
Maribavir is extensively metabolized following oral administration, primarily by CYP3A4 and, to a lesser extent, by CYP1A2.5 Its major circulating metabolite is VP 44469, an inactive N-dealkylated metabolite.5
Hover over products below to view reaction partners
- Route of elimination
Maribavir is eliminated primarily via hepatic metabolism.5 Following the oral administration of radiolabeled maribavir, 61% of the dose was excreted in the urine (<2% as unchanged drug) and 14% was excreted in the feces (5.7% as unchanged drug).5
- Half-life
In post-transplant patients, the mean half-life of elimination was 4.32 hours.5
- Clearance
In post-transplant patients, the mean oral clearance of maribavir was 2.85 L/h.5
- Adverse Effects
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Data are limited regarding overdosage with maribavir. As there is no specific antidote for maribavir overdose, patients suspected of overdosage should be monitored closely for adverse reactions and treated symptomatically as clinically indicated.5 As maribavir is extensively protein-bound in plasma, dialysis is unlikely to be of benefit.5
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Maribavir can be increased when it is combined with Abametapir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Maribavir. Adenovirus type 7 vaccine live The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Maribavir. Afatinib The serum concentration of Afatinib can be increased when it is combined with Maribavir. Allopurinol Maribavir may decrease the excretion rate of Allopurinol which could result in a higher serum level. - Food Interactions
- Avoid St. John's Wort. Co-administration with St. John's wort decreases serum levels of maribavir and may decrease its therapeutic efficacy.
- Take with or without food. The co-administration of food with maribavir does not significantly affect its disposition.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Camvia (ViroPharma Inc.) / Livtencity (Takeda Pharmaceuticals America, Inc.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Livtencity Tablet, coated 200 mg/1 Oral Takeda Pharmaceuticals America, Inc. 2021-11-23 Not applicable US 
Livtencity Tablet, film coated 200 mg Oral Takeda Pharmaceuticals International Ag Ireland Branch 2023-02-08 Not applicable EU 
Livtencity Tablet, film coated 200 mg Oral Takeda Pharmaceuticals International Ag Ireland Branch 2023-02-08 Not applicable EU Livtencity Tablet 200 mg Oral Takeda 2022-10-25 Not applicable Canada 
Livtencity Tablet, film coated 200 mg Oral Takeda Pharmaceuticals International Ag Ireland Branch 2023-02-08 Not applicable EU
Categories
- ATC Codes
- J05AX10 — Maribavir
- Drug Categories
- Anti-Infective Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- BCRP/ABCG2 Inhibitors
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Cytomegalovirus pUL97 Kinase Inhibitor
- Direct Acting Antivirals
- Glycosides
- Heterocyclic Compounds, Fused-Ring
- Nucleic Acids, Nucleotides, and Nucleosides
- Nucleosides
- P-glycoprotein inhibitors
- Ribonucleosides
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzimidazole ribonucleosides and ribonucleotides. These are nucleosides with a structure that consists of an imidazole moiety of benzimidazole is N-linked to a ribose (or deoxyribose). Nucleotides have a phosphate group linked to the C5 carbon of the ribose (or deoxyribose) moiety.
- Kingdom
- Organic compounds
- Super Class
- Nucleosides, nucleotides, and analogues
- Class
- Benzimidazole ribonucleosides and ribonucleotides
- Sub Class
- Not Available
- Direct Parent
- Benzimidazole ribonucleosides and ribonucleotides
- Alternative Parents
- Glycosylamines / Pentoses / Benzimidazoles / Secondary alkylarylamines / N-substituted imidazoles / Aminoimidazoles / Benzenoids / Aryl chlorides / Heteroaromatic compounds / Tetrahydrofurans show 7 more
- Substituents
- 1-ribofuranosylbenzimidazole / Alcohol / Amine / Aminoimidazole / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Azole / Benzenoid show 23 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- HHV-5
Chemical Identifiers
- UNII
- PTB4X93HE1
- CAS number
- 176161-24-3
- InChI Key
- KJFBVJALEQWJBS-XUXIUFHCSA-N
- InChI
- InChI=1S/C15H19Cl2N3O4/c1-6(2)18-15-19-9-3-7(16)8(17)4-10(9)20(15)14-13(23)12(22)11(5-21)24-14/h3-4,6,11-14,21-23H,5H2,1-2H3,(H,18,19)/t11-,12-,13-,14-/m0/s1
- IUPAC Name
- (2S,3S,4R,5S)-2-{5,6-dichloro-2-[(propan-2-yl)amino]-1H-1,3-benzodiazol-1-yl}-5-(hydroxymethyl)oxolane-3,4-diol
- SMILES
- CC(C)NC1=NC2=CC(Cl)=C(Cl)C=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O
References
- Synthesis Reference
Glover BN, Huang LF, Lancaster RW, Long ST, Rizzolio MC, Schmitt EA, Sickles BR. (2010). Crystalline forms of an antiviral benzimidazole compound (US Patent No. US7714123B2).
- General References
- Sun K, Welty D: Elucidation of Metabolic and Disposition Pathways for Maribavir in Nonhuman Primates through Mass Balance and Semi-Physiologically Based Modeling Approaches. Drug Metab Dispos. 2021 Nov;49(11):1025-1037. doi: 10.1124/dmd.121.000493. Epub 2021 Aug 30. [Article]
- Goldwater DR, Dougherty C, Schumacher M, Villano SA: Effect of ketoconazole on the pharmacokinetics of maribavir in healthy adults. Antimicrob Agents Chemother. 2008 May;52(5):1794-8. doi: 10.1128/AAC.00951-07. Epub 2008 Mar 3. [Article]
- Koszalka GW, Johnson NW, Good SS, Boyd L, Chamberlain SC, Townsend LB, Drach JC, Biron KK: Preclinical and toxicology studies of 1263W94, a potent and selective inhibitor of human cytomegalovirus replication. Antimicrob Agents Chemother. 2002 Aug;46(8):2373-80. doi: 10.1128/AAC.46.8.2373-2380.2002. [Article]
- Hakki M: Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy. Curr Hematol Malig Rep. 2020 Apr;15(2):90-102. doi: 10.1007/s11899-020-00557-6. [Article]
- FDA Approved Drug Products: Livtencity (maribavir) tablets for oral use [Link]
- FDA News Release: FDA Approves First Treatment for Common Type of Post-Transplant Infection that is Resistant to Other Drugs [Link]
- Health Canada Approved Drug Products: LIVTENCITY (maribavir) Oral Tablets [Link]
- EMA Approved Drug Products: LIVTENCITY (maribavir) Oral Tablets [Link]
- Takeda: European Commission (EC) Approves LIVTENCITYTM▼ (maribavir) for the Treatment of Adults With Post-transplant Cytomegalovirus (CMV) Infection And/or Disease That Are Refractory (With or Without Resistance) to One or More Prior Therapies [Link]
- External Links
- ChemSpider
- 413807
- 2586068
- ChEMBL
- CHEMBL515408
- ZINC
- ZINC000003824412
- Wikipedia
- Maribavir
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Recruiting Prevention CMV / Transplantation complications 1 3 Completed Prevention Cytomegalovirus (CMV) Infections 2 3 Completed Treatment Cytomegalovirus (CMV) 3 3 Recruiting Treatment Cytomegalovirus (CMV) 1 2 Completed Prevention Cytomegalovirus (CMV) Infections 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 200 mg Tablet, coated Oral 200 mg/1 Tablet, film coated Oral 200 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US11684632 No 2012-01-04 2032-01-04 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.72 mg/mL ALOGPS logP 2.15 ALOGPS logP 1.84 Chemaxon logS -2.7 ALOGPS pKa (Strongest Acidic) 12.45 Chemaxon pKa (Strongest Basic) 6.38 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 99.77 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 90.01 m3·mol-1 Chemaxon Polarizability 37.49 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-002f-0095000000-6ef44332dfa1629cdc72 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00e9-0079000000-ff97fec70a7880b739f7 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-052f-0092000000-274a477099d51a662b4e Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0gx3-0293000000-7f44a4abd9c0a2e9adbb Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0zmi-1196000000-2ed5cf55d4a0a300485c Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0059-3792000000-1db97438d94e9bb7faa0 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 177.5251 predictedDeepCCS 1.0 (2019) [M+H]+ 179.92067 predictedDeepCCS 1.0 (2019) [M+Na]+ 187.14189 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- HHV-5
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Protein kinase activity
- Specific Function
- Serine/threonine protein kinase that plays important roles in several processes including nuclear viral egress, viral replication or regulation of host cell cycle progression. Participates in the a...
- Gene Name
- UL97
- Uniprot ID
- P16788
- Uniprot Name
- Serine/threonine protein kinase UL97
- Molecular Weight
- 78231.9 Da
References
- FDA Approved Drug Products: Livtencity (maribavir) tablets for oral use [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: Livtencity (maribavir) tablets for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- FDA Approved Drug Products: Livtencity (maribavir) tablets for oral use [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Koszalka GW, Johnson NW, Good SS, Boyd L, Chamberlain SC, Townsend LB, Drach JC, Biron KK: Preclinical and toxicology studies of 1263W94, a potent and selective inhibitor of human cytomegalovirus replication. Antimicrob Agents Chemother. 2002 Aug;46(8):2373-80. doi: 10.1128/AAC.46.8.2373-2380.2002. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Not Available
- Specific Function
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23511.38 Da
References
- Koszalka GW, Johnson NW, Good SS, Boyd L, Chamberlain SC, Townsend LB, Drach JC, Biron KK: Preclinical and toxicology studies of 1263W94, a potent and selective inhibitor of human cytomegalovirus replication. Antimicrob Agents Chemother. 2002 Aug;46(8):2373-80. doi: 10.1128/AAC.46.8.2373-2380.2002. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- FDA Approved Drug Products: Livtencity (maribavir) tablets for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: Livtencity (maribavir) tablets for oral use [Link]
Drug created at March 19, 2008 16:18 / Updated at December 23, 2022 00:49