Bictegravir

Identification

Summary

Bictegravir is an integrase inhibitor used to treat HIV infections.

Brand Names
Biktarvy
Generic Name
Bictegravir
DrugBank Accession Number
DB11799
Background

Bictegravir is a recently approved investigational drug that has been used in trials studying the treatment of HIV-1 and HIV-2 infection. It has been approved for HIV-1 monotherapy combined with 2 other antiretrovirals in a single tablet.7

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 449.386
Monoisotopic: 449.119855181
Chemical Formula
C21H18F3N3O5
Synonyms
  • Bictegravir
External IDs
  • GS-9883
  • GS-9883-01

Pharmacology

Indication

Bictegravir is indicated in the management of HIV-1 infection in patients not previously treated with antiretroviral therapy. Additionally, Bictegravir is indicated in the management of HIV-1 infection in patients who are virologically suppressed (HIV-1 RNA <50 c/mL) on a regular antiretroviral regimen for a minimum of three months without a history of failure in treatment and no known factors associated with the resistance to the individual components of the medication. It is used in combination with tenofovir and emtricitabine.3,4,8

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatHuman immunodeficiency virus type 1 (hiv-1) infectionCombination Product in combination with: Emtricitabine (DB00879), Tenofovir alafenamide (DB09299)••••••••••••••••••••••••• •••••••••• •••••• ••• •••• •••• •• •••••• ••• •••• •••••• •• ••••• •• ••• •• ••••••• •• ••••••••• •••••••• •••••• •••••••••••••• •••••••••••••
Used in combination to treatHuman immunodeficiency virus type 1 (hiv-1) infectionCombination Product in combination with: Tenofovir alafenamide (DB09299), Emtricitabine (DB00879)•••••••••••••••••• ••••••••••••••• •• ••••• •• ••• •••••••••••••• ••••••••• •••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Bictegravir is an HIV-1 integrase strand transfer inhibitor (INSTI). Bictegravir (BIC) inhibits HIV-1 virus replication into the human genome. It can be taken once daily without additional dosing 2,3,4,5. Bictegravir (BIC) inhibits strand transfer of viral DNA into the host genome and thereby prevents HIV-1 replication 5.

Mechanism of action

This single dose medication inhibits the strand transfer of viral DNA into the human genome, preventing HIV-1 virus replication and propagation 2.

In vitro, bictegravir has shown powerful antiviral activity against HIV-2 and various subtypes of HIV-1. It has shown synergistic effects when combined with other ARVs, including tenofovir alafenamide (TAF), emtricitabine (FTC), and darunavir (DRV). The three components of the first USA approved medication ( trade name: Biktarvy ) are as follows:

Bictegravir: integrase strand transfer inhibitor; INSTI), an HIV-1 encoded enzyme necessary for viral replication. Inhibition of the integrase enzyme prevents the integration of HIV-1 into host DNA, blocking the conversion of the HIV-1 provirus and progression of the virus Label.

Emtricitabine: FTC, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine is phosphorylated to form emtricitabine 5'-triphosphate intracellularly. This metabolite inhibits the activity of human immunodeficiency virus (HIV) reverse transcriptase by competing with the substrate deoxycytidine 5'-triphosphate and by incorporating itself into viral DNA preventing DNA chain elongation Label.

Tenofovir Alafenamide: TAF is a phosphonamidate prodrug of tenofovir (2′-deoxyadenosine monophosphate analog). Plasma exposure to TAF leads to leakage into cells and then TAF is intracellularly converted to tenofovir by hydrolysis by cathepsin. Tenofovir is subsequently phosphorylated by cellular kinases to the metabolite tenofovir diphosphate, which is the active form of the drug. Tenofovir diphosphate inhibits HIV-1 replication by incorporating into viral DNA by the HIV reverse transcriptase, resulting in DNA chain-termination. Tenofovir diphosphate also weakly inhibits mammalian DNA polymerases Label.

TargetActionsOrganism
AReverse transcriptase/RNaseH
antagonist
Human immunodeficiency virus 1
AIntegrase
antagonist
Human immunodeficiency virus 1
Absorption

Bictegravir is rapidly absorbed within the body. Tmax= 2.0-4.0h 3

Volume of distribution

0.2 L/Kg in humans 2

Protein binding

> 99 % bound to human plasma Blood to plasma ratio: 0.64 2

Metabolism

In a 10-day dose-ranging study, monotherapy (5 mg to 100 mg) once daily in adults who were not previously treated with bictegravir, the median half-life of BIC ranged from 15.9 h - 20.9 h 3. Bictegravir is metabolized in the liver and kidneys. CYP3A4 and UGT1A are the primary enzymes involved in the metabolism of bictegravir. Administration of bictegravir is not advised in patients with renal creatinine clearance of <30 mL/min and patients with hepatic disease Label.

Route of elimination

BIC is mainly eliminated through UGT1A1 glucuronidation and CYP3A4 oxidation, equally 2. About 1% of the bictegravir dose is excreted in the urine, unchanged 2,3.

Half-life

Half-life is 17.3 hours.6

Clearance

Bictegravir is mainly cleared by the kidneys. Those with renal clearance <30 should not take bictegravir Label

Adverse Effects
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Toxicity

Those with renal disease and creatinine clearance of <30 mL/min should not take bictegravir Label. Patients with hepatic disease should not take bictegravir.

Most common adverse reactions include diarrhea, nausea, and headache Label.

Lactic acidosis/severe hepatomegaly with steatosis: Discontinue treatment in patients who develop symptoms/laboratory findings suggesting lactic acidosis or hepatotoxicity.

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.
DrugInteraction
AbametapirThe serum concentration of Bictegravir can be increased when it is combined with Abametapir.
AbemaciclibThe excretion of Abemaciclib can be decreased when combined with Bictegravir.
AcyclovirThe excretion of Acyclovir can be decreased when combined with Bictegravir.
AdenineThe metabolism of Bictegravir can be decreased when combined with Adenine.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Bictegravir.
Food Interactions
  • Avoid St. John's Wort.
  • Take at the same time every day.
  • Take separate from antacids. Take bictegravir at least 2 hours before or 6 hours after taking antacids containing aluminum or magnesium.
  • Take with food. When taking iron or calcium-containing products, bictegravir should be taken with food.
  • Take with or without food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Bictegravir sodium4L5MP1Y7W71807988-02-8WJNFBIVCQMPPJC-FQYDJHLKSA-M
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BiktarvyBictegravir sodium (50 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide fumarate (25 mg)Tablet, film coatedOralGilead Sciences Ireland Uc2021-06-01Not applicableEU flag
BIKTARVYBictegravir (50 MG) + Emtricitabine (200 MG) + Tenofovir alafenamide (25 MG)Tablet, film coatedOralGilead Sciences Ireland Uc2019-01-29Not applicableItaly flag
BiktarvyBictegravir sodium (50 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide fumarate (25 mg)TabletOralGilead Sciences2018-08-08Not applicableCanada flag
BiktarvyBictegravir sodium (50 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide fumarate (25 mg/1)TabletOralREMEDYREPACK INC.2021-04-28Not applicableUS flag
BiktarvyBictegravir sodium (50 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide fumarate (25 mg)Tablet, film coatedOralGilead Sciences Ireland Uc2020-12-15Not applicableEU flag

Categories

ATC Codes
J05AR20 — Emtricitabine, tenofovir alafenamide and bictegravir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyridinecarboxylic acids and derivatives. These are compounds containing a pyridine ring bearing a carboxylic acid group or a derivative thereof.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Pyridinecarboxylic acids and derivatives
Direct Parent
Pyridinecarboxylic acids and derivatives
Alternative Parents
2-heteroaryl carboxamides / 1,3-oxazepines / Hydroxypyridines / Fluorobenzenes / 1,3-oxazinanes / Aryl fluorides / Vinylogous amides / Vinylogous acids / Tertiary carboxylic acid amides / Heteroaromatic compounds
show 9 more
Substituents
1,3-oxazinane / 2-heteroaryl carboxamide / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Carboxamide group / Carboxylic acid derivative / Cyclic ketone
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Human Immunodeficiency Virus

Chemical Identifiers

UNII
8GB79LOJ07
CAS number
1611493-60-7
InChI Key
SOLUWJRYJLAZCX-LYOVBCGYSA-N
InChI
InChI=1S/C21H18F3N3O5/c22-9-3-14(23)12(15(24)4-9)6-25-20(30)13-7-26-8-16-27(10-1-2-11(5-10)32-16)21(31)17(26)19(29)18(13)28/h3-4,7,10-11,16,29H,1-2,5-6,8H2,(H,25,30)/t10-,11+,16+/m0/s1
IUPAC Name
(1S,11R,13R)-5-hydroxy-3,6-dioxo-N-[(2,4,6-trifluorophenyl)methyl]-12-oxa-2,9-diazatetracyclo[11.2.1.0^{2,11}.0^{4,9}]hexadeca-4,7-diene-7-carboxamide
SMILES
OC1=C2N(C[C@H]3O[C@@H]4CC[C@@H](C4)N3C2=O)C=C(C(=O)NCC2=C(F)C=C(F)C=C2F)C1=O

References

General References
  1. Chase SP, Freimanis AK: Abdominal echography. Ohio State Med J. 1971 Oct;67(10):901-6. [Article]
  2. Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1–Infected Adults [Link]
  3. BICTEGRAVIR [Link]
  4. FDA APPROVES BIKTARVY [Link]
  5. BICTEGRAVIR SODIUM [Link]
  6. FDA Approved Drug Products: BIKTARVY (bictegravir, emtricitabine, and tenofovir alafenamide) tablets, for oral use [Link]
  7. FDA Approved Drug Products: BIKTARVY (bictegravir, emtricitabine, and tenofovir alafenamide) tablets, for oral use (October 2022) [Link]
  8. EMA Approved Drug Products: Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) Oral Tablets [Link]
PubChem Compound
90311989
PubChem Substance
347828148
ChemSpider
44208822
BindingDB
330048
RxNav
1999660
ChEBI
172943
ChEMBL
CHEMBL3989866
PDBe Ligand
KLQ
Wikipedia
Bictegravir
PDB Entries
6puw / 6rwm / 6rwo / 7ouh
FDA label
Download (720 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingHealth Services ResearchHuman Immunodeficiency Virus (HIV) Infections1
4Active Not RecruitingTreatmentAcute HIV Infection1
4Active Not RecruitingTreatmentDrug Use / Human Immunodeficiency Virus (HIV) Infections / Reduction, Harm1
4Active Not RecruitingTreatmentHIV-infected Patient Kidney Transplant Recipient1
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral
Tablet, coatedOral
Tablet, film coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6642245Yes2003-11-042021-05-04US flag
US6703396Yes2004-03-092021-09-09US flag
US9296769Yes2016-03-292033-02-15US flag
US7803788No2010-09-282022-02-02US flag
US8754065Yes2014-06-172033-02-15US flag
US7390791Yes2008-06-242025-10-17US flag
US9216996No2015-12-222033-12-19US flag
US9708342No2017-07-182035-06-19US flag
US9732092No2017-08-152033-12-19US flag
US10385067No2019-08-202035-06-19US flag
US10548846No2020-02-042036-11-08US flag
US11744802No2016-11-082036-11-08US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
boiling point (°C)682.5±55.0 °C at 760 mmHg[L1221]
Predicted Properties
PropertyValueSource
Water Solubility0.0537 mg/mLALOGPS
logP1.28ALOGPS
logP1.36Chemaxon
logS-3.9ALOGPS
pKa (Strongest Acidic)9.81Chemaxon
pKa (Strongest Basic)-0.3Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area99.18 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity105.44 m3·mol-1Chemaxon
Polarizability41.14 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
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/MSsplash10-0006-0090000000-f7664c9a47d6001aa621
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-0033900000-3261c687e9a3ce0a6042
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000l-0190100000-31cb555762b0823317fe
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03mj-0131900000-c811dd4a24fca6977230
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0fc0-0970100000-992dfacc024c47617ab9
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-1392400000-bda5c48565024141ed21
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-192.42169
predicted
DeepCCS 1.0 (2019)
[M+H]+194.81728
predicted
DeepCCS 1.0 (2019)
[M+Na]+200.72978
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Antagonist
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
Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q7ZJM1
Uniprot Name
Integrase
Molecular Weight
32226.645 Da

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function
Transcription factor that specifically binds to the octamer motif (5'-ATTTGCAT-3'). Regulates transcription in a number of tissues in addition to activating immunoglobulin gene expression. Modulate...
Gene Name
POU2F2
Uniprot ID
P09086
Uniprot Name
POU domain, class 2, transcription factor 2
Molecular Weight
51208.51 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Biktarvy FDA label [File]

Drug created at October 20, 2016 20:49 / Updated at December 06, 2022 13:40