tenofovir alafenamide Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
antivirals phosphonic acid derivatives 4944 379270-37-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • GS 7340
  • tenofovir alagenamide
  • tenofovir alafenamide
  • tenofovir alafenamide fumarate
  • GS-7340
a phosphonoamidate prodrug of tenofovir (2'deoxyadenosine monophosphate analog). Plasma exposure to tenofovir alafenamide allows for permeation into cells and then tenofovir alafenamide is intracellularly converted to tenofovir through hydrolysis by cathepsin A. Tenofovir is subsequently phosphorylated by cellular kinases to the active metabolite tenofovir diphosphate. Tenofovir diphosphate inhibits HIV replication through incorporation into viral DNA by the HIV reverse transcriptase, which results in DNA chain-termination
  • Molecular weight: 476.47
  • Formula: C21H29N6O5P
  • CLOGP: 2.18
  • LIPINSKI: 1
  • HAC: 11
  • HDO: 2
  • TPSA: 143.48
  • ALOGS: -3.30
  • ROTB: 12

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
25 mg O

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Feb. 20, 2014 EMA
Nov. 5, 2015 FDA GILEAD SCIENCES INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Maternal exposure during pregnancy 359.35 23.62 164 3120 102385 46580393
Weight increased 141.74 23.62 106 3178 164367 46518411
Abortion spontaneous 137.08 23.62 65 3219 43581 46639197
Blood HIV RNULL increased 88.66 23.62 18 3266 669 46682109
Viral load increased 81.48 23.62 19 3265 1356 46681422
Genotype drug resistance test positive 74.48 23.62 15 3269 535 46682243
Product use complaint 71.28 23.62 18 3266 1794 46680984
Product dispensing error 59.77 23.62 23 3261 9210 46673568
Drug interaction 51.26 23.62 67 3217 203027 46479751
Gastrointestinal tube insertion 48.38 23.62 12 3272 1111 46681667
Foetal exposure during pregnancy 43.42 23.62 27 3257 30720 46652058
Gastrostomy 39.70 23.62 9 3275 566 46682212
Exposure during pregnancy 35.82 23.62 41 3243 108171 46574607
CD4 lymphocytes decreased 34.94 23.62 10 3274 1600 46681178
Abortion induced 31.27 23.62 15 3269 10245 46672533
Treatment noncompliance 29.59 23.62 21 3263 29710 46653068
Product storage error 29.29 23.62 15 3269 11777 46671001
Immune reconstitution inflammatory syndrome 29.16 23.62 12 3272 5713 46677065
Headache 25.05 23.62 82 3202 478270 46204508

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Viral load increased 421.80 17.91 109 8794 2745 29940830
Product storage error 251.86 17.91 88 8815 6303 29937272
Weight increased 241.21 17.91 190 8713 74723 29868852
Blood HIV RNULL increased 218.48 17.91 56 8847 1360 29942215
Gastrointestinal tube insertion 209.14 17.91 53 8850 1228 29942347
Immune reconstitution inflammatory syndrome 183.86 17.91 77 8826 9024 29934551
Product dispensing error 175.55 17.91 66 8837 5823 29937752
CD4 lymphocytes decreased 127.69 17.91 40 8863 2030 29941545
Product dose omission issue 88.68 17.91 122 8781 91509 29852066
Gastrostomy 75.09 17.91 21 8882 715 29942860
Rash 70.13 17.91 167 8736 191722 29751853
Product use complaint 69.95 17.91 22 8881 1130 29942445
HIV infection 65.78 17.91 23 8880 1645 29941930
Abnormal dreams 63.79 17.91 36 8867 8079 29935496
Syphilis 63.26 17.91 16 8887 367 29943208
Drug interaction 61.69 17.91 163 8740 199405 29744170
Viraemia 57.24 17.91 19 8884 1160 29942415
Endotracheal intubation 57.17 17.91 23 8880 2427 29941148
Genotype drug resistance test positive 55.41 17.91 20 8883 1569 29942006
Therapy cessation 51.97 17.91 40 8863 15097 29928478
Intentional dose omission 49.93 17.91 18 8885 1407 29942168
Treatment noncompliance 48.66 17.91 48 8855 25205 29918370
Nausea 43.75 17.91 189 8714 296768 29646807
Insomnia 42.70 17.91 89 8814 93247 29850328
HIV viraemia 42.19 17.91 9 8894 94 29943481
Virologic failure 41.78 17.91 20 8883 3199 29940376
Nightmare 41.64 17.91 32 8871 12044 29931531
Hypothalamic pituitary adrenal axis suppression 40.60 17.91 10 8893 205 29943370
Fat tissue increased 40.17 17.91 11 8892 346 29943229
Inability to afford medication 39.51 17.91 13 8890 772 29942803
HIV test positive 38.79 17.91 10 8893 248 29943327
Wrong technique in product usage process 38.69 17.91 47 8856 31108 29912467
Insurance issue 38.67 17.91 13 8890 825 29942750
Dysphagia 35.73 17.91 62 8841 56636 29886939
Headache 35.66 17.91 127 8776 182179 29761396
Product dispensing issue 34.60 17.91 7 8896 55 29943520
Fanconi syndrome acquired 33.31 17.91 15 8888 2088 29941487
Mechanical ventilation 32.91 17.91 14 8889 1700 29941875
Blood triglycerides increased 29.54 17.91 28 8875 13989 29929586
Liver function test increased 28.73 17.91 25 8878 11191 29932384
Drug resistance 27.67 17.91 32 8871 20101 29923474
Hepatitis B DNULL increased 27.62 17.91 9 8894 518 29943057
Product temperature excursion issue 26.25 17.91 4 8899 3 29943572
Suicidal ideation 26.09 17.91 42 8861 36072 29907503
Renal tubular dysfunction 25.85 17.91 8 8895 389 29943186
Glomerular filtration rate decreased 24.52 17.91 23 8880 11339 29932236
Therapy change 24.43 17.91 13 8890 2596 29940979
Sleep disorder 24.21 17.91 33 8870 24446 29919129
Circumstance or information capable of leading to medication error 23.91 17.91 11 8892 1608 29941967
Abdominal distension 23.75 17.91 46 8857 45663 29897912
Hemiparaesthesia 23.54 17.91 5 8898 51 29943524
Heart transplant rejection 23.28 17.91 10 8893 1243 29942332
Hypotension 22.68 17.91 16 8887 200549 29743026
Alopecia 22.18 17.91 28 8875 19247 29924328
Depression 22.09 17.91 68 8835 90369 29853206
Product distribution issue 21.93 17.91 6 8897 188 29943387
Intercepted product dispensing error 21.47 17.91 5 8898 80 29943495
Mental disorder 21.26 17.91 23 8880 13426 29930149
Renal tubular disorder 21.16 17.91 15 8888 4991 29938584
Hospitalisation 21.09 17.91 43 8860 44276 29899299
Lung transplant rejection 20.64 17.91 8 8895 764 29942811
Blood HIV RNULL 20.05 17.91 4 8899 29 29943546
Acquired immunodeficiency syndrome 19.93 17.91 7 8896 507 29943068
Blood creatinine increased 19.85 17.91 66 8837 91309 29852266
Pneumonia 18.89 17.91 45 8858 334261 29609314
Product use issue 18.84 17.91 42 8861 45974 29897601
Osteoporosis 18.21 17.91 19 8884 10644 29932931

Pharmacologic Action:

SourceCodeDescription
ATC J05AF13 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Nucleoside and nucleotide reverse transcriptase inhibitors
ATC J05AR17 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
ATC J05AR18 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
ATC J05AR19 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
ATC J05AR20 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
ATC J05AR22 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
CHEBI has role CHEBI:36044 anti-virus drug
CHEBI has role CHEBI:50266 prodrugs
CHEBI has role CHEBI:53756 reverse transcriptase inhibitor

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Human immunodeficiency virus infection indication 86406008 DOID:526

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.86 Basic
pKa2 3.96 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
150MG;800MG;200MG;EQ 10MG BASE SYMTUZA JANSSEN PRODS N210455 July 17, 2018 RX TABLET ORAL July 17, 2021 NEW COMBINULLTION
150MG;150MG;200MG;EQ 10MG BASE GENVOYA GILEAD SCIENCES INC N207561 Nov. 5, 2015 RX TABLET ORAL Dec. 10, 2021 DOSING RECOMMENDATION FOR THE USE OF ELVITEGRAVIR/COBICISTAT/EMTRICITABINE/TENOFOVIR ALAFENULLMIDE FIXED DOSE COMBINULLTION IN HIV-1 INFECTED ADULT PATIENTS WITH END-STAGE-RENULLL DISEASE WHO ARE RECEIVING CHRONIC HEMODIALYSIS
EQ 50MG BASE;200MG;EQ 25MG BASE BIKTARVY GILEAD SCIENCES INC N210251 Feb. 7, 2018 RX TABLET ORAL June 18, 2022 NEW PATIENT POPULATION
200MG;EQ 25MG BASE DESCOVY GILEAD SCIENCES INC N208215 April 4, 2016 RX TABLET ORAL Oct. 3, 2022 FOR USE IN AT RISK ADULTS AND ADOLESCENTS WEIGHING AT LEAST 35 KG FOR PRE-EXPOSURE PROPHYLAXIS TO REDUCE THE RISK OF HIV-1 INFECTION FROM SEXUAL ACQUISITION, EXCLUDING INDIVIDUALS AT RISK FROM RECEPTIVE VAGINULLL SEX
EQ 25MG BASE VEMLIDY GILEAD SCIENCES INC N208464 Nov. 10, 2016 RX TABLET ORAL Feb. 4, 2023 INFORMATION ADDED TO THE LABELING TO DESCRIBE STUDY GS-US-320-4018 IN VIROLOGICALLY SUPPRESSED ADULTS W/ CHRONIC HEP B INFECTION WHO SWITCHED FROM TENOFOVIR DISOPROXIL FUMARATE TO TENOFOVIR ALAFENULLMIDE
EQ 50MG BASE;200MG;EQ 25MG BASE BIKTARVY GILEAD SCIENCES INC N210251 Feb. 7, 2018 RX TABLET ORAL Feb. 7, 2023 NEW CHEMICAL ENTITY
EQ 25MG BASE VEMLIDY GILEAD SCIENCES INC N208464 Nov. 10, 2016 RX TABLET ORAL Aug. 22, 2023 INFORMATION ADDED TO THE LABELING TO DESCRIBE STUDY GS-US-320-4035 IN VIROLOGICALLY SUPPRESSED ADULTS W/ CHRONIC HEP B INFECTION WHO SWITCHED FROM TENOFOVIR DISOPROXIL FUMARATE TO TENOFOVIR ALFAENULLMIDE
EQ 50MG BASE;200MG;EQ 25MG BASE BIKTARVY GILEAD SCIENCES INC N210251 Feb. 7, 2018 RX TABLET ORAL Feb. 24, 2024 LABELING REVISIONS RELATED TO CLINICAL STUDIES
200MG;EQ 25MG BASE DESCOVY GILEAD SCIENCES INC N208215 April 4, 2016 RX TABLET ORAL Sept. 28, 2024 IN COMBINULLTION WITH OTHER ANTIRETROVIRAL AGENTS, FOR THE TREATMENT OF HIV-1 INFECTION IN PEDIATRIC PATIENTS UNDER 12 YEARS OF AGE WEIGHING AT LEAST 35KG
200MG;EQ 25MG BASE DESCOVY GILEAD SCIENCES INC N208215 April 4, 2016 RX TABLET ORAL Sept. 28, 2024 IN COMBINULLTION WITH OTHER ANTIRETROVIRAL AGENTS OTHER THAN PROTEASE INHIBITORS THAT REQUIRE A CYP3A INHIBITOR, FOR THE TREATMENT OF HIV-1 INFECTION IN PEDIATRIC PATIENTS UNDER 12 YEARS OF AGE WEIGHING AT LEAST 25KG AND LESS THAN 35KG
EQ 50MG BASE;200MG;EQ 25MG BASE BIKTARVY GILEAD SCIENCES INC N210251 Feb. 7, 2018 RX TABLET ORAL June 18, 2026 FOR HIV-1 INFECTION IN PEDIATRIC PTS AT LEAST 25 KG W/ NO ANTIRETROVIRAL (ARV) TX HX OR TO REPLACE CURRENT ARV REGIMEN FOR VIROLOGICALLY-SUPPRESSED ON STABLE ARV W/ NO HX TX FAILURE AND NO KNOWN SUBSTITUTIONS ASSOCIATED W/ RESISTANCE TO BIC, FTC, OR TAF

Bioactivity Summary:

None

External reference:

IDSource
D10428 KEGG_DRUG
1392275-56-7 SECONDARY_CAS_RN
4035188 VANDF
C1100128 UMLSCUI
CHEBI:90926 CHEBI
CHEMBL2107825 ChEMBL_ID
CHEMBL2364637 ChEMBL_ID
C442442 MESH_SUPPLEMENTAL_RECORD_UI
9980 INN_ID
DB09299 DRUGBANK_ID
EL9943AG5J UNII
9574767 PUBCHEM_CID
1721603 RXNORM
31269 MMSL
31575 MMSL
016564 NDDF
715220007 SNOMEDCT_US
734973002 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Symtuza HUMAN PRESCRIPTION DRUG LABEL 4 59676-800 TABLET, FILM COATED 10 mg ORAL NDA 33 sections
Genvoya HUMAN PRESCRIPTION DRUG LABEL 4 61958-1901 TABLET 10 mg ORAL NDA 32 sections
DESCOVY HUMAN PRESCRIPTION DRUG LABEL 2 61958-2002 TABLET 25 mg ORAL NDA 35 sections
ODEFSEY HUMAN PRESCRIPTION DRUG LABEL 3 61958-2101 TABLET 25 mg ORAL NDA 35 sections
VEMLIDY HUMAN PRESCRIPTION DRUG LABEL 1 61958-2301 TABLET 25 mg ORAL NDA 35 sections
Biktarvy HUMAN PRESCRIPTION DRUG LABEL 3 61958-2501 TABLET 25 mg ORAL NDA 35 sections
DESCOVY HUMAN PRESCRIPTION DRUG LABEL 2 70518-0230 TABLET 25 mg ORAL NDA 32 sections
Genvoya HUMAN PRESCRIPTION DRUG LABEL 4 70518-0568 TABLET 10 mg ORAL NDA 31 sections
Biktarvy HUMAN PRESCRIPTION DRUG LABEL 3 70518-3080 TABLET 25 mg ORAL NDA 34 sections