letermovir 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| antivirals | 5262 | 917389-32-3 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
Letermovir inhibits the CMV DNA terminase complex (pUL51, pUL56, and pUL89) which is required for viral DNA processing and packaging. Biochemical characterization and electron microscopy demonstrated that letermovir affects the production of proper unit length genomes and interferes with virion maturation. Genotypic characterization of virus resistant to letermovir confirmed that letermovir targets the terminase complex.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 0.48 | g | O |
| 0.48 | g | P |
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| S (Water solubility) | 0.35 mg/mL | Bocci G, Oprea TI, Benet LZ |
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 4 | Bocci G, Oprea TI, Benet LZ |
| BA (Bioavailability) | 0.94 % | Kawashima H, Watanabe R, Esaki T, Kuroda M, Nagao C, Natsume-Kitatani Y, Ohashi R, Komura H, Mizuguchi K |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Jan. 8, 2018 | EMA | Merck Sharp & Dohme Limited | |
| Nov. 8, 2017 | FDA | MERCK SHARP DOHME | |
| March 23, 2018 | PMDA | MSD KK |
FDA Adverse Event Reporting System (Female)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Cytomegalovirus infection reactivation | 196.24 | 56.21 | 37 | 1068 | 3926 | 63483991 |
| Off label use | 91.44 | 56.21 | 82 | 1023 | 674380 | 62813537 |
| Pathogen resistance | 89.34 | 56.21 | 21 | 1084 | 6377 | 63481540 |
| Cytomegalovirus viraemia | 86.58 | 56.21 | 20 | 1085 | 5629 | 63482288 |
| Post transplant lymphoproliferative disorder | 57.22 | 56.21 | 14 | 1091 | 5017 | 63482900 |
FDA Adverse Event Reporting System (Male)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Cytomegalovirus infection reactivation | 163.52 | 61.89 | 38 | 1279 | 5080 | 34950534 |
| Off label use | 108.86 | 61.89 | 103 | 1214 | 419421 | 34536193 |
| Pathogen resistance | 108.08 | 61.89 | 31 | 1286 | 9451 | 34946163 |
| Oesophagitis | 89.59 | 61.89 | 29 | 1288 | 13232 | 34942382 |
| Encephalitis cytomegalovirus | 63.02 | 61.89 | 12 | 1305 | 606 | 34955008 |
FDA Adverse Event Reporting System (Geriatric)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Cytomegalovirus infection reactivation | 333.65 | 50.82 | 72 | 2327 | 8644 | 79733345 |
| Off label use | 174.53 | 50.82 | 171 | 2228 | 907044 | 78834945 |
| Pathogen resistance | 174.35 | 50.82 | 47 | 2352 | 14295 | 79727694 |
| Cytomegalovirus viraemia | 132.52 | 50.82 | 37 | 2362 | 12784 | 79729205 |
| Drug resistance | 92.70 | 50.82 | 38 | 2361 | 42175 | 79699814 |
| Oesophagitis | 86.10 | 50.82 | 31 | 2368 | 24258 | 79717731 |
| Cytomegalovirus infection | 82.24 | 50.82 | 35 | 2364 | 42609 | 79699380 |
| Thrombotic microangiopathy | 68.69 | 50.82 | 25 | 2374 | 20144 | 79721845 |
| Cystitis haemorrhagic | 66.02 | 50.82 | 20 | 2379 | 9152 | 79732837 |
| Encephalitis cytomegalovirus | 64.15 | 50.82 | 13 | 2386 | 1137 | 79740852 |
| Graft versus host disease | 64.02 | 50.82 | 22 | 2377 | 15004 | 79726985 |
| Acute graft versus host disease in skin | 60.75 | 50.82 | 18 | 2381 | 7640 | 79734349 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | J05AX18 | ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Other antivirals |
| MeSH PA | D000890 | Anti-Infective Agents |
| MeSH PA | D000970 | Antineoplastic Agents |
| MeSH PA | D000998 | Antiviral Agents |
| MeSH PA | D004791 | Enzyme Inhibitors |
| MeSH PA | D000067856 | Poly(ADP-ribose) Polymerase Inhibitors |
| FDA MoA | N0000185507 | Cytochrome P450 2C9 Inducers |
| FDA MoA | N0000185607 | Cytochrome P450 2C19 Inducers |
| FDA MoA | N0000187062 | Cytochrome P450 2C8 Inhibitors |
| FDA MoA | N0000190107 | Organic Anion Transporting Polypeptide 1B1 Inhibitors |
| FDA MoA | N0000190108 | Organic Anion Transporting Polypeptide 1B3 Inhibitors |
| FDA MoA | N0000190114 | Cytochrome P450 3A Inhibitors |
| FDA EPC | N0000193800 | Cytomegalovirus DNA Terminase Complex Inhibitor |
| FDA MoA | N0000193801 | DNA Terminase Complex Inhibitors |
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Cytomegalovirus infection | indication | 28944009 |
🐶 Veterinary Drug Use
None
🐶 Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 5.4 | acidic |
| pKa2 | 6.77 | Basic |
| pKa3 | 4.76 | Basic |
Orange Book patent data (new drug applications)
None
Orange Book exclusivity data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
|---|---|---|---|---|---|---|---|---|---|
| 240MG | PREVYMIS | MERCK SHARP DOHME | N209939 | Nov. 8, 2017 | RX | TABLET | ORAL | Nov. 8, 2024 | PROPHYLAXIS OF CYTOMEGALOVIRUS (CMV) INFECTION AND DISEASE IN ADULT CMV-SEROPOSITIVE RECIPIENTS [R+] OF AN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) |
| 480MG | PREVYMIS | MERCK SHARP DOHME | N209939 | Nov. 8, 2017 | RX | TABLET | ORAL | Nov. 8, 2024 | PROPHYLAXIS OF CYTOMEGALOVIRUS (CMV) INFECTION AND DISEASE IN ADULT CMV-SEROPOSITIVE RECIPIENTS [R+] OF AN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) |
| 240MG/12ML (20MG/ML) | PREVYMIS | MERCK SHARP DOHME | N209940 | Nov. 8, 2017 | RX | SOLUTION | INTRAVENOUS | Nov. 8, 2024 | PROPHYLAXIS OF CYTOMEGALOVIRUS (CMV) INFECTION AND DISEASE IN ADULT CMV-SEROPOSITIVE RECIPIENTS [R+] OF AN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) |
| 480MG/24ML (20MG/ML) | PREVYMIS | MERCK SHARP DOHME | N209940 | Nov. 8, 2017 | RX | SOLUTION | INTRAVENOUS | Nov. 8, 2024 | PROPHYLAXIS OF CYTOMEGALOVIRUS (CMV) INFECTION AND DISEASE IN ADULT CMV-SEROPOSITIVE RECIPIENTS [R+] OF AN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) |
| 240MG | PREVYMIS | MERCK SHARP DOHME | N209939 | Nov. 8, 2017 | RX | TABLET | ORAL | June 5, 2026 | PROPHYLAXIS OF CYTOMEGALOVIRUS (CMV) DISEASE IN ADULT KIDNEY TRANSPLANT RECIPIENTS AT HIGH RISK (DONOR CMV SEROPOSITIVE/RECIPIENT CMV SERONEGATIVE [D+/R-]) |
| 480MG | PREVYMIS | MERCK SHARP DOHME | N209939 | Nov. 8, 2017 | RX | TABLET | ORAL | June 5, 2026 | PROPHYLAXIS OF CYTOMEGALOVIRUS (CMV) DISEASE IN ADULT KIDNEY TRANSPLANT RECIPIENTS AT HIGH RISK (DONOR CMV SEROPOSITIVE/RECIPIENT CMV SERONEGATIVE [D+/R-]) |
| 240MG/12ML (20MG/ML) | PREVYMIS | MERCK SHARP DOHME | N209940 | Nov. 8, 2017 | RX | SOLUTION | INTRAVENOUS | June 5, 2026 | PROPHYLAXIS OF CYTOMEGALOVIRUS (CMV) DISEASE IN ADULT KIDNEY TRANSPLANT RECIPIENTS AT HIGH RISK (DONOR CMV SEROPOSITIVE/RECIPIENT CMV SERONEGATIVE [D+/R-]) |
| 480MG/24ML (20MG/ML) | PREVYMIS | MERCK SHARP DOHME | N209940 | Nov. 8, 2017 | RX | SOLUTION | INTRAVENOUS | June 5, 2026 | PROPHYLAXIS OF CYTOMEGALOVIRUS (CMV) DISEASE IN ADULT KIDNEY TRANSPLANT RECIPIENTS AT HIGH RISK (DONOR CMV SEROPOSITIVE/RECIPIENT CMV SERONEGATIVE [D+/R-]) |
| 240MG | PREVYMIS | MERCK SHARP DOHME | N209939 | Nov. 8, 2017 | RX | TABLET | ORAL | June 5, 2030 | FOR PROPHYLAXIS OF CYTOMEGALOVIRUS (CMV) DISEASE IN ADULT KIDNEY TRANSPLANT RECIPIENTS AT HIGH RISK (DONOR CMV SEROPOSITIVE/RECIPIENT CMV SERONEGATIVE [D+/R-]) |
| 480MG | PREVYMIS | MERCK SHARP DOHME | N209939 | Nov. 8, 2017 | RX | TABLET | ORAL | June 5, 2030 | FOR PROPHYLAXIS OF CYTOMEGALOVIRUS (CMV) DISEASE IN ADULT KIDNEY TRANSPLANT RECIPIENTS AT HIGH RISK (DONOR CMV SEROPOSITIVE/RECIPIENT CMV SERONEGATIVE [D+/R-]) |
| 240MG/12ML (20MG/ML) | PREVYMIS | MERCK SHARP DOHME | N209940 | Nov. 8, 2017 | RX | SOLUTION | INTRAVENOUS | June 5, 2030 | FOR PROPHYLAXIS OF CYTOMEGALOVIRUS (CMV) DISEASE IN ADULT KIDNEY TRANSPLANT RECIPIENTS AT HIGH RISK (DONOR CMV SEROPOSITIVE/RECIPIENT CMV SERONEGATIVE [D+/R-]) |
| 480MG/24ML (20MG/ML) | PREVYMIS | MERCK SHARP DOHME | N209940 | Nov. 8, 2017 | RX | SOLUTION | INTRAVENOUS | June 5, 2030 | FOR PROPHYLAXIS OF CYTOMEGALOVIRUS (CMV) DISEASE IN ADULT KIDNEY TRANSPLANT RECIPIENTS AT HIGH RISK (DONOR CMV SEROPOSITIVE/RECIPIENT CMV SERONEGATIVE [D+/R-]) |
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| DNA terminase complex | Enzyme | INHIBITOR | EC50 | 8.68 | DRUG LABEL | DRUG LABEL |
External reference:
| ID | Source |
|---|---|
| 1H09Y5WO1F | UNII |
| 4037136 | VANDF |
| C3852938 | UMLSCUI |
| CHEMBL1241951 | ChEMBL_ID |
| 45138674 | PUBCHEM_CID |
| DB12070 | DRUGBANK_ID |
| D10801 | KEGG_DRUG |
| 9384 | INN_ID |
| 265515 | MMSL |
| 33254 | MMSL |
| d08676 | MMSL |
| 017399 | NDDF |
| 763033005 | SNOMEDCT_US |
| 763568003 | SNOMEDCT_US |
| 1988648 | RXNORM |
| C000588473 | MESH_SUPPLEMENTAL_RECORD_UI |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| PREVYMIS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0006-3075 | TABLET, FILM COATED | 240 mg | ORAL | NDA | 31 sections |
| PREVYMIS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0006-3075 | TABLET, FILM COATED | 240 mg | ORAL | NDA | 31 sections |
| PREVYMIS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0006-3075 | TABLET, FILM COATED | 240 mg | ORAL | NDA | 31 sections |
| PREVYMIS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0006-3076 | TABLET, FILM COATED | 480 mg | ORAL | NDA | 31 sections |
| PREVYMIS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0006-3076 | TABLET, FILM COATED | 480 mg | ORAL | NDA | 31 sections |
| PREVYMIS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0006-3076 | TABLET, FILM COATED | 480 mg | ORAL | NDA | 31 sections |
| PREVYMIS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0006-5003 | INJECTION, SOLUTION | 20 mg | INTRAVENOUS | NDA | 31 sections |
| PREVYMIS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0006-5003 | INJECTION, SOLUTION | 20 mg | INTRAVENOUS | NDA | 31 sections |
| PREVYMIS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0006-5003 | INJECTION, SOLUTION | 20 mg | INTRAVENOUS | NDA | 31 sections |
| PREVYMIS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0006-5004 | INJECTION, SOLUTION | 20 mg | INTRAVENOUS | NDA | 31 sections |
| PREVYMIS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0006-5004 | INJECTION, SOLUTION | 20 mg | INTRAVENOUS | NDA | 31 sections |
| PREVYMIS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0006-5004 | INJECTION, SOLUTION | 20 mg | INTRAVENOUS | NDA | 31 sections |