Identification

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Name
Tenofovir alafenamide
Accession Number
DB09299
Type
Small Molecule
Groups
Approved
Description

Tenofovir alafenamide is a novel tenofovir prodrug developed in order to improve renal safety when compared to the counterpart tenofovir disoproxil.1 Both of these prodrugs were first created to cover the polar phosphonic acid group on tenofovir by using a novel oxycarbonyloxymethyl linkers to improve the oral bioavailability and intestinal diffusion.8 Tenofovir alafenamide is an alanine ester form characterized for presenting low systemic levels but high intracellular concentration.2 It has been reported to produce a large antiviral efficacy at doses ten times lower than tenofovir disoproxil.6

The first approved product including tenofovir alafenamide was developed by Gilead Sciences Inc and FDA approved on 2015.10

Structure
Thumb
Synonyms
  • Tenofovir alafenamide
External IDs
GS 7340 / GS 7340 03 / GS 734003 / GS-7340 / GS-7340-03 / GS-734003 / GS7340 / GS734003
Product Ingredients
IngredientUNIICASInChI Key
Tenofovir alafenamide fumarateFWF6Q91TZO1392275-56-7SVUJNSGGPUCLQZ-FQQAACOVSA-N
Active Moieties
NameKindUNIICASInChI Key
TenofovirprodrugW4HFE001U5147127-20-6SGOIRFVFHAKUTI-ZCFIWIBFSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
OdefseyTablet, film coatedOralGilead Sciences Ireland Uc2016-06-21Not applicableEu
OdefseyTablet, film coatedOralGilead Sciences Ireland Uc2016-06-21Not applicableEu
VemlidyTablet25 mg/1OralGilead Sciences, Inc.2016-11-10Not applicableUs
VemlidyTablet25 mgOralGilead Sciences2017-06-20Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
BiktarvyTenofovir alafenamide fumarate (25 mg/1) + Bictegravir sodium (50 mg/1) + Emtricitabine (200 mg/1)TabletOralGilead Sciences, Inc.2018-02-07Not applicableUs
DescovyTenofovir alafenamide (10 mg) + Emtricitabine (200 mg)TabletOralGilead Sciences2016-06-03Not applicableCanada
DescovyTenofovir alafenamide fumarate (25 mg/1) + Emtricitabine (200 mg/1)TabletOralGilead Sciences2016-04-04Not applicableUs
DescovyTenofovir alafenamide fumarate (25 mg/1) + Emtricitabine (200 mg/1)TabletOralREMEDYREPACK INC.2019-02-16Not applicableUs
DescovyTenofovir alafenamide (25 mg) + Emtricitabine (200 mg)TabletOralGilead Sciences2016-06-03Not applicableCanada
GenvoyaTenofovir alafenamide (10 mg) + Cobicistat (150 mg) + Elvitegravir (150 mg) + Emtricitabine (200 mg)Tablet, film coatedOralGilead Sciences Ireland Uc2015-11-19Not applicableEu
GenvoyaTenofovir alafenamide fumarate (10 mg/1) + Cobicistat (150 mg/1) + Elvitegravir (150 mg/1) + Emtricitabine (200 mg/1)TabletOralA-S Medication Solutions2015-11-05Not applicableUs
GenvoyaTenofovir alafenamide fumarate (10 mg/1) + Cobicistat (150 mg/1) + Elvitegravir (150 mg/1) + Emtricitabine (200 mg/1)TabletOralREMEDYREPACK INC.2017-06-06Not applicableUs
GenvoyaTenofovir alafenamide fumarate (10 mg/1) + Cobicistat (150 mg/1) + Elvitegravir (150 mg/1) + Emtricitabine (200 mg/1)TabletOralGilead Sciences, Inc.2015-11-05Not applicableUs
GenvoyaTenofovir alafenamide (10 mg) + Cobicistat (150 mg) + Elvitegravir (150 mg) + Emtricitabine (200 mg)Tablet, film coatedOralGilead Sciences Ireland Uc2015-11-19Not applicableEu
Categories
UNII
J4414G3BUK
CAS number
379270-37-8
Weight
Average: 476.474
Monoisotopic: 476.193705056
Chemical Formula
C21H29N6O5P
InChI Key
LDEKQSIMHVQZJK-CAQYMETFSA-N
InChI
InChI=1S/C21H29N6O5P/c1-14(2)31-21(28)16(4)26-33(29,32-17-8-6-5-7-9-17)13-30-15(3)10-27-12-25-18-19(22)23-11-24-20(18)27/h5-9,11-12,14-16H,10,13H2,1-4H3,(H,26,29)(H2,22,23,24)/t15-,16+,33+/m1/s1
IUPAC Name
propan-2-yl (2S)-2-{[(S)-({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)(phenoxy)phosphoryl]amino}propanoate
SMILES
CC(C)OC(=O)[C@H](C)N[P@](=O)(CO[C@H](C)CN1C=NC2=C(N)N=CN=C12)OC1=CC=CC=C1

Pharmacology

Indication

Tenofovir alafenamide is indicated for the treatment of chronic hepatitis B in adult patients with compensated liver disease.9

In combination with emtricitabine and other antiretrovirals, it is indicated for the treatment of HIV-1 infection in patients with a weight higher than 35 kg. When combined with antiretrovirals other than protease inhibitors that require a CYP3A inhibitor, it can be used in pediatric patients weighing between 25 and 35 kg.11

In the combination product with emtricitabine and bictegravir, tenofovir alafenamide is considered as a complete regimen for the treatment of HIV-1 infection in treatment-naive patients or in patients virologically suppressed for at least 3 months with no history of treatment failure.12

Additionally, the combination product including elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide and the combination product including emtricitabine, rilpivirine and tenofovir alafenamide can be used in the treatment of HIV-1 infection in patients older than 12 years with no previous antiretroviral therapy history or who are virologically suppressed for at least 6 months with no history of treatment failure.13

Lastly, the combination product including darunavir, cobicistat, emtricitabine, and tenofovir alafenamide is indicated for the treatment of HIV-1 infection in adults without prior antiretroviral therapy or in patients virologically suppressed for 6 months and no reported resistance to darunavir or tenofovir.14

Associated Conditions
Pharmacodynamics

Tenofovir alafenamide has been shown to be a potent inhibitor of the hepatitis B virus replication.4

Tenofovir alafenamide presents a better renal tolerance when compared with the counterpart tenofovir disoproxil. This improved safety profile seems to be related to a lower plasma concentration of tenofovir.1

In clinical trials, tenofovir alafenamide was shown to present 5-fold more potent antiviral activity against HIV-1 when compared to tenofovir disoproxil.1

Mechanism of action

Tenofovir alafenamide presents even a 91% lower plasma concentration with an intracellular presence of about 20-fold higher when compared to tenofovir disoproxil.2 It is a great alternative to obtain a higher potency against viral-target cells. This is due to its prolonged systemic exposure and its driven higher intracellular accumulation of the active metabolite tenofovir diphosphate.5

Tenofovir alafenamide mechanism of action has been studied and it has been reported that this prodrug presents a high accumulation in peripheral blood mononuclear cells when compared to red blood cells.5

Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase causing chain termination and the inhibition of viral synthesis.9 To know more about the specific mechanism of action of the active form, please visit the drug entry of tenofovir.

TargetActionsOrganism
AReverse transcriptase/RNaseH
inhibitor
Human immunodeficiency virus 1
NReverse transcriptase
inhibitor
HBV
NDNA polymerase
inhibitor
Human herpesvirus 2 (strain 186)
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

As compared to the parent molecule, tenofovir, tenofovir alafenamide presents a lipophilic group that masks the negative charge of the parent moiety which in order improves its oral bioavailability.1

Due to the molecular properties of tenofovir alafenamide, this molecule is highly stable in the plasma and, after administration of this prodrug, there is a low concentration of tenofovir in plasma. After oral administration, tenofovir alafenamide is rapidly absorbed by the gut. When a single dose is administered, a peak concentration of 16 ng/ml of the parent compound, corresponding to about 73% of the dose, is observed after 2 hours with an AUC of 270 ng.h/ml.1,5 Once inside the body, tenofovir alafenamide enters hepatocytes by passive diffusion regulated by the organic anion transporters 1B1 and 1B3 for its activation.4

Administration of tenofovir alafenamide concomitantly with a high-fat meal results in an increase of about 65% in its internal exposure.15

Volume of distribution

In clinical trials, the reported volume of distribution of tenofovir alafenamide was higher than 100 L.7

Protein binding

Tenofovir alafenamide is reported to bind to plasma proteins and ex vivo studies have registered that approximately 80% of the administered dose of this drug is presented in a bound state.3

Metabolism

To be activated, tenofovir alafenamide is required to be hydrolyzed to the parent compound tenofovir by the activity of cathepsin A or carboxylesterase 1. Tenofovir alafenamide presents significant plasma stability and hence, its activation is performed inside the target cells.1

After activation, tenofovir is further processed and after 1-2 days, it is detected in plasma almost completely transformed to uric acid.1

Route of elimination

Tenofovir alafenamide has been registered to present a bile elimination that corresponds to 47% of the administered dose and a renal elimination the represents about 36%. From the recovered dose in urine, about 75% is represented as unchanged tenofovir followed by uric acid and a small dose of tenofovir alafenamide. On the other hand, in feces, 99% of the recovered dose corresponds to tenofovir.1

Half life

The reported half-life for tenofovir alafenamide is of 0.51 hours.3

Clearance

The reported clearance rate of tenofovir alafenamide us of 117 L/h. In patients with severe renal impairment, this value can be found to be decreased by 50% reporting a rate of 61.7 L/h.16

Toxicity

The LD50 of tenofovir alafenamide has not been reported. In cases of overdose, continuous monitoring of vital signs is required as the adverse effects in high doses has not been evaluated. However, in case of overdose, tenofovir is efficiently removed by hemodialysis with an extraction coefficient of 54%.15

Carcinogenic reports have only been performed with tenofovir disoproxil and it is important to consider that tenofovir alafenamide does not present a high systemic exposure. However, long-term exposure with 10-fold dosages of tenofovir disoproxil was reported to produce liver adenomas in females. Tenofovir alafenamide was not reported to present mutagenic potential and it did not present effects on fertility.15

Affected organisms
  • Herpes simplex virus
  • Hepatitis B virus
  • HIV-1
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirTenofovir alafenamide may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbemaciclibThe serum concentration of Tenofovir alafenamide can be increased when it is combined with Abemaciclib.
AcarboseTenofovir alafenamide may decrease the excretion rate of Acarbose which could result in a higher serum level.
AcebutololThe serum concentration of Tenofovir alafenamide can be increased when it is combined with Acebutolol.
AceclofenacAceclofenac may increase the nephrotoxic activities of Tenofovir alafenamide.
AcemetacinAcemetacin may increase the nephrotoxic activities of Tenofovir alafenamide.
AcetaminophenTenofovir alafenamide may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideThe excretion of Tenofovir alafenamide can be decreased when combined with Acetazolamide.
AcetylcysteineThe excretion of Tenofovir alafenamide can be decreased when combined with Acetylcysteine.
Acetylsalicylic acidAcetylsalicylic acid may increase the nephrotoxic activities of Tenofovir alafenamide.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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  • Action
    Evidence Level

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
  1. Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [PubMed:27438578]
  2. Grant PM, Cotter AG: Tenofovir and bone health. Curr Opin HIV AIDS. 2016 May;11(3):326-32. doi: 10.1097/COH.0000000000000248. [PubMed:26859637]
  3. Deeks ED: Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. [PubMed:30460547]
  4. Ogawa E, Furusyo N, Nguyen MH: Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy. Drug Des Devel Ther. 2017 Nov 6;11:3197-3204. doi: 10.2147/DDDT.S126742. eCollection 2017. [PubMed:29158666]
  5. Ray AS, Fordyce MW, Hitchcock MJ: Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27. [PubMed:26640223]
  6. Antela A, Aguiar C, Compston J, Hendry BM, Boffito M, Mallon P, Pourcher-Martinez V, Di Perri G: The role of tenofovir alafenamide in future HIV management. HIV Med. 2016 May;17 Suppl 2:4-16. doi: 10.1111/hiv.12401. [PubMed:26952360]
  7. Markowitz M, Zolopa A, Squires K, Ruane P, Coakley D, Kearney B, Zhong L, Wulfsohn M, Miller MD, Lee WA: Phase I/II study of the pharmacokinetics, safety and antiretroviral activity of tenofovir alafenamide, a new prodrug of the HIV reverse transcriptase inhibitor tenofovir, in HIV-infected adults. J Antimicrob Chemother. 2014 May;69(5):1362-9. doi: 10.1093/jac/dkt532. Epub 2014 Feb 6. [PubMed:24508897]
  8. Wolpe P. and Howard J. (2007). Comprehensive Medicinal Chemistry II. Elsevier.
  9. Pubmed books [Link]
  10. FDA approvals [Link]
  11. DESCOVY® (emtricitabine and tenofovir alafenamide) FDA label [Link]
  12. FDA label [Link]
  13. FDA label [Link]
  14. FDA label [Link]
  15. DPD label [Link]
  16. EMA labels [Link]
External Links
KEGG Drug
D10428
PubChem Compound
9574768
PubChem Substance
310265191
ChemSpider
7849225
ChEBI
90926
ChEMBL
CHEMBL2107825
Wikipedia
Tenofovir_alafenamide
ATC Codes
J05AR19 — Emtricitabine, tenofovir alafenamide and rilpivirineJ05AR20 — Emtricitabine, tenofovir alafenamide and bictegravirJ05AR17 — Emtricitabine and tenofovir alafenamideJ05AF13 — Tenofovir alafenamideJ05AR22 — Emtricitabine, tenofovir alafenamide, darunavir and cobicistatJ05AR18 — Emtricitabine, tenofovir alafenamide, elvitegravir and cobicistat
AHFS Codes
  • 08:18.08.20 — Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
FDA label
Download (1.08 MB)
MSDS
Download (254 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingBasic ScienceHealthy Volunteers1
1Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I1
1CompletedHealth Services ResearchHuman Immunodeficiency Virus (HIV)1
1CompletedPreventionHealthy Volunteers1
1CompletedPreventionHuman Immunodeficiency Virus (HIV)1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentHepatitis B Chronic Infection1
1CompletedTreatmentHepatitis B Virus (HBV)1
1RecruitingBasic ScienceAmyotrophic Lateral Sclerosis (ALS)1
1RecruitingBasic ScienceHealthy Volunteers1
1RecruitingPreventionHuman Immunodeficiency Virus (HIV) Infections1
1RecruitingTreatmentInsulin Resistance1
1, 2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2Active Not RecruitingTreatmentHIV and Hepatitis B Coinfection1
2Active Not RecruitingTreatmentHIV-1-infection1
2Active Not RecruitingTreatmentHepatitis B Chronic Infection3
2CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections2
2CompletedTreatmentInfection, Human Immunodeficiency Virus I1
2Not Yet RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Large-B-cell Diffuse Lymphoma1
2Not Yet RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2RecruitingTreatmentHepatitis B Chronic Infection3
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
2TerminatedTreatmentHBV / Human Immunodeficiency Virus (HIV)1
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
2, 3RecruitingTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
2, 3RecruitingTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
2, 3RecruitingTreatmentInfection, Human Immunodeficiency Virus I1
3Active Not RecruitingOtherViral Hepatitis B1
3Active Not RecruitingTreatmentChronic HBV Infections / Chronic Infection With HIV / HBV1
3Active Not RecruitingTreatmentChronic HBV Infections / HBV3
3Active Not RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV)1
3Active Not RecruitingTreatmentHIV-1-infection2
3Active Not RecruitingTreatmentHepatitis B Chronic Infection1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
3Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I8
3Active Not RecruitingTreatmentPre-Exposure Prophylaxis of HIV-1 Infection1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1)1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHBV / Human Immunodeficiency Virus (HIV)1
3CompletedTreatmentHIV Risk1
3CompletedTreatmentHepatitis C Virus (HCV) Infection / Infection, Human Immunodeficiency Virus I1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections3
3CompletedTreatmentInfection, Human Immunodeficiency Virus I7
3RecruitingPreventionHepatitis B Virus Positive / Malignant Solid Neoplasm1
3RecruitingTreatmentHIV-1/HBV Co-Infection1
3RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
3RecruitingTreatmentHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
4Active Not RecruitingTreatmentHepatitis B Chronic Infection1
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV)2
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4Active Not RecruitingTreatmentViral Hepatitis B1
4CompletedOtherHuman Immunodeficiency Virus (HIV)1
4Not Yet RecruitingTreatmentAcute HIV Infection1
4Not Yet RecruitingTreatmentBone Loss1
4Not Yet RecruitingTreatmentViral Hepatitis B1
4Not Yet RecruitingTreatmentViral Hepatitis B / Virus Hepatitis1
4RecruitingPreventionHepatitis B Virus Infection1
4RecruitingTreatmentBone Diseases, Metabolic / Chronic Hepatitis C Virus (HCV) Infection / Co-Infection / HIV-1-infection / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS) / Intravenous Drug Usage / Methadone Dependence / Opioid Dependence / Substance Abuse1
4RecruitingTreatmentFibrosis and Cirrhosis of Liver / Viral Hepatitis B1
4RecruitingTreatmentHIV-1-infection1
4RecruitingTreatmentHIV-1-infection / Viral Hepatitis B1
4RecruitingTreatmentHepatitis B Chronic Infection2
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections3
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections / Severe Immunosuppression1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Menopause / Osteoporosis1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Renal Insufficiency,Chronic / Therapeutic Agent Toxicity1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV)1
Not AvailableNot Yet RecruitingNot AvailableAntiviral Drug Adverse Reaction / Viral Hepatitis B1
Not AvailableNot Yet RecruitingNot AvailableHepatitis B Chronic Infection1
Not AvailableNot Yet RecruitingTreatmentHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
Not AvailableRecruitingNot AvailableAcute-On-Chronic Liver Failure / Hepatic Failure / Viral Hepatitis B / Virus Diseases1
Not AvailableRecruitingNot AvailableBone Diseases / Chronic Hepatitis B in HIV Patient / Kidney Injury1
Not AvailableRecruitingNot AvailableCardiovascular Disease (CVD) / HIV-1-infection / Hyperglycemias / Metabolic Syndromes / Renal Function Abnormal / Weight gain therapy1
Not AvailableRecruitingNot AvailableHIV-1-infection1
Not AvailableRecruitingNot AvailableHepatitis B Chronic Infection1
Not AvailableRecruitingNot AvailableHepatitis B, Chronic / Hepatitis C Viral Infection1
Not AvailableRecruitingNot AvailableHuman Immunodeficiency Virus (HIV)2
Not AvailableRecruitingTreatmentAcute-On-Chronic Liver Failure / Viral Hepatitis B1
Not AvailableRecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
Tablet, film coatedOral
Tablet, film coatedOral
TabletOral25 mg/1
TabletOral25 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7800788No2010-09-212022-02-02Us
US5914331Yes1999-06-222018-01-02Us
US5814639Yes1998-09-292017-03-29Us
US6642245Yes2003-11-042021-05-04Us
US6703396Yes2004-03-092021-09-09Us
US7470506Yes2008-12-302019-12-23Us
US8597876Yes2013-12-032019-12-23Us
US7700645Yes2010-04-202027-06-26Us
US8518987Yes2013-08-272024-08-16Us
US7125879No2006-10-242022-08-09Us
US6838464No2005-01-042021-02-26Us
US8080551No2011-12-202023-04-11Us
US8101629No2012-01-242022-08-09Us
US7067522No2006-06-272019-12-20Us
US8148374No2012-04-032029-09-03Us
US7635704No2009-12-222026-10-26Us
US7176220No2007-02-132023-11-20Us
US8981103No2015-03-172026-10-26Us
US8633219No2014-01-212030-04-24Us
US9296769No2016-03-292032-08-15Us
US7803788No2010-09-282022-02-02Us
US8754065No2014-06-172032-08-15Us
US7390791No2008-06-242022-05-07Us
US9891239No2018-02-132029-09-03Us
US9889115Yes2018-02-132019-12-23Us
US9216996No2015-12-222033-12-19Us
US9708342No2017-07-182035-06-19Us
US9732092No2017-08-152033-12-19Us
US10039718No2018-08-072032-10-04Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)104-107 ºC'MSDS'
boiling point (°C)640 ºC at 760 mmHg'MSDS'
water solubility4.86 mg/ml at 20 ºCProduct monograph. Gilead Sciences Canada
logP1.6Product monograph. Gilead Sciences Canada
pKa3.96Product monograph. Gilead Sciences Canada
Predicted Properties
PropertyValueSource
Water Solubility0.236 mg/mLALOGPS
logP1.49ALOGPS
logP1.88ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)11.36ChemAxon
pKa (Strongest Basic)5.12ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area143.48 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity122.74 m3·mol-1ChemAxon
Polarizability47.88 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid esters
Alternative Parents
Alanine and derivatives / 6-aminopurines / Phenoxy compounds / Aminopyrimidines and derivatives / Phosphonic amide esters / Phosphonic acid esters / N-substituted imidazoles / Imidolactams / Heteroaromatic compounds / Carboxylic acid esters
show 8 more
Substituents
Alpha-amino acid ester / Alanine or derivatives / 6-aminopurine / Purine / Imidazopyrimidine / Phenoxy compound / Aminopyrimidine / Phosphonic acid ester / Monocyclic benzene moiety / N-substituted imidazole
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rna-dna hybrid ribonuclease activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72547
Uniprot Name
Reverse transcriptase/RNaseH
Molecular Weight
65223.615 Da
References
  1. McConville C, Boyd P, Major I: Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection. Clin Med Insights Womens Health. 2014 Feb 13;7:1-8. doi: 10.4137/CMWH.S10353. eCollection 2014. [PubMed:24741339]
  2. Ray AS, Fordyce MW, Hitchcock MJ: Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27. [PubMed:26640223]
2. Reverse transcriptase
Kind
Protein
Organism
HBV
Pharmacological action
No
Actions
Inhibitor
References
  1. McConville C, Boyd P, Major I: Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection. Clin Med Insights Womens Health. 2014 Feb 13;7:1-8. doi: 10.4137/CMWH.S10353. eCollection 2014. [PubMed:24741339]
  2. Ray AS, Fordyce MW, Hitchcock MJ: Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27. [PubMed:26640223]
3. DNA polymerase
Kind
Protein
Organism
Human herpesvirus 2 (strain 186)
Pharmacological action
No
Actions
Inhibitor
References
  1. McConville C, Boyd P, Major I: Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection. Clin Med Insights Womens Health. 2014 Feb 13;7:1-8. doi: 10.4137/CMWH.S10353. eCollection 2014. [PubMed:24741339]
  2. Ray AS, Fordyce MW, Hitchcock MJ: Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27. [PubMed:26640223]

Enzymes

Kind
Protein
Organism
Not Available
Pharmacological action
No
Actions
Substrate
General Function
Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins.
Specific Function
Carboxypeptidase activity
Gene Name
CTSA
Uniprot ID
P10619
Uniprot Name
Lysosomal protective protein
Molecular Weight
54465.655 Da
References
  1. Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [PubMed:27438578]
  2. Deeks ED: Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. [PubMed:30460547]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [PubMed:27438578]
  2. Deeks ED: Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. [PubMed:30460547]
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
  1. FDA label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Nucleoside diphosphate kinase activity
Specific Function
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Also displays broad nucleoside diphosphate kinase activity. Plays an important role in cellular energy homeost...
Gene Name
AK1
Uniprot ID
P00568
Uniprot Name
Adenylate kinase isoenzyme 1
Molecular Weight
21634.725 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Atp binding
Specific Function
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. Adenylate kinase ...
Gene Name
AK2
Uniprot ID
P54819
Uniprot Name
Adenylate kinase 2, mitochondrial
Molecular Weight
26477.44 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Ribosomal small subunit binding
Specific Function
Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-sit...
Gene Name
NME1
Uniprot ID
P15531
Uniprot Name
Nucleoside diphosphate kinase A
Molecular Weight
17148.635 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Transcription factor activity, sequence-specific dna binding
Specific Function
Major role in the synthesis of nucleoside triphosphates other than ATP. Negatively regulates Rho activity by interacting with AKAP13/LBC. Acts as a transcriptional activator of the MYC gene; binds ...
Gene Name
NME2
Uniprot ID
P22392
Uniprot Name
Nucleoside diphosphate kinase B
Molecular Weight
17297.935 Da

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
  1. Deeks ED: Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. [PubMed:30460547]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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
  1. Soriano V, Labarga P, Fernandez-Montero JV, Mendoza C, Benitez-Gutierrez L, Pena JM, Barreiro P: Drug interactions in HIV-infected patients treated for hepatitis C. Expert Opin Drug Metab Toxicol. 2017 Aug;13(8):807-816. doi: 10.1080/17425255.2017.1351942. Epub 2017 Jul 13. [PubMed:28689442]
  2. Begley R, Das M, Zhong L, Ling J, Kearney BP, Custodio JM: Pharmacokinetics of Tenofovir Alafenamide When Coadministered With Other HIV Antiretrovirals. J Acquir Immune Defic Syndr. 2018 Aug 1;78(4):465-472. doi: 10.1097/QAI.0000000000001699. [PubMed:29649076]
  3. Custodio JM, Fordyce M, Garner W, Vimal M, Ling KH, Kearney BP, Ramanathan S: Pharmacokinetics and Safety of Tenofovir Alafenamide in HIV-Uninfected Subjects with Severe Renal Impairment. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5135-40. doi: 10.1128/AAC.00005-16. Print 2016 Sep. [PubMed:27216057]
  4. Murakami E, Wang T, Park Y, Hao J, Lepist EI, Babusis D, Ray AS: Implications of efficient hepatic delivery by tenofovir alafenamide (GS-7340) for hepatitis B virus therapy. Antimicrob Agents Chemother. 2015;59(6):3563-9. doi: 10.1128/AAC.00128-15. Epub 2015 Apr 13. [PubMed:25870059]
  5. Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [PubMed:27438578]
  6. HIV insite, UCSF: Tenofovir Alafenamide [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [PubMed:27438578]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [PubMed:27438578]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [PubMed:27438578]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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
  1. Deeks ED: Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. [PubMed:30460547]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Ogawa E, Furusyo N, Nguyen MH: Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy. Drug Des Devel Ther. 2017 Nov 6;11:3197-3204. doi: 10.2147/DDDT.S126742. eCollection 2017. [PubMed:29158666]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Ogawa E, Furusyo N, Nguyen MH: Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy. Drug Des Devel Ther. 2017 Nov 6;11:3197-3204. doi: 10.2147/DDDT.S126742. eCollection 2017. [PubMed:29158666]

Drug created on November 08, 2015 14:16 / Updated on May 21, 2019 12:25