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.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Bictegravir (DB11799)
- 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.
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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.
Target Actions Organism AReverse transcriptase/RNaseH antagonistHuman immunodeficiency virus 1 AIntegrase antagonistHuman 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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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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Bictegravir can be increased when it is combined with Abametapir. Abemaciclib The excretion of Abemaciclib can be decreased when combined with Bictegravir. Acyclovir The excretion of Acyclovir can be decreased when combined with Bictegravir. Adenine The metabolism of Bictegravir can be decreased when combined with Adenine. Adenovirus type 7 vaccine live The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Bictegravir. Amiodarone The metabolism of Bictegravir can be decreased when combined with Amiodarone. Amitriptyline The metabolism of Bictegravir can be decreased when combined with Amitriptyline. Amprenavir The metabolism of Bictegravir can be decreased when combined with Amprenavir. Anthrax vaccine The therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Bictegravir. Apalutamide The metabolism of Bictegravir can be increased when combined with Apalutamide. 
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- 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
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.- Product Ingredients
Ingredient UNII CAS InChI Key Bictegravir sodium 4L5MP1Y7W7 1807988-02-8 WJNFBIVCQMPPJC-FQYDJHLKSA-M - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image BIKTARVY Bictegravir (50 MG) + Emtricitabine (200 MG) + Tenofovir alafenamide (25 MG) Tablet, coated Oral บริษัท ดีซีเอช ออริกา (ประเทศไทย) จำกัด 2020-01-02 Not applicable Thailand 
Biktarvy Bictegravir sodium (50 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide fumarate (25 mg) Tablet, film coated Oral Gilead Sciences Ireland Uc 2020-12-15 Not applicable EU 
Biktarvy Bictegravir sodium (50 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide fumarate (25 mg) Tablet Oral Gilead Sciences 2018-08-08 Not applicable Canada 
Biktarvy Bictegravir sodium (50 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide fumarate (25 mg/1) Tablet Oral REMEDYREPACK INC. 2021-04-28 Not applicable US 
Biktarvy Bictegravir sodium (50 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide fumarate (25 mg/1) Tablet Oral Gilead Sciences, Inc. 2018-02-07 Not applicable US Biktarvy Bictegravir sodium (50 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide fumarate (25 mg) Tablet, film coated Oral Gilead Sciences Ireland Uc 2021-06-01 Not applicable EU Biktarvy Bictegravir sodium (50 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide fumarate (25 mg) Tablet, film coated Oral Gilead Sciences Ireland Uc 2020-12-15 Not applicable EU Biktarvy Bictegravir sodium (30 mg/1) + Emtricitabine (120 mg/1) + Tenofovir alafenamide fumarate (15 mg/1) Tablet Oral Gilead Sciences, Inc. 2021-10-07 Not applicable US Biktarvy Bictegravir sodium (50 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide fumarate (25 mg) Tablet, film coated Oral Gilead Sciences Ireland Uc 2021-06-01 Not applicable EU BİKTARVY 50 MG / 200 MG / 25 MG FİLM KAPLI TABLET, 30 TABLET Bictegravir (50 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide (25 mg) Tablet, coated Oral GİLEAD SCİENCES İLAÇ TİC. LTD. ŞTİ. 2020-08-14 Not applicable Turkey 
Categories
- ATC Codes
- J05AR20 — Emtricitabine, tenofovir alafenamide and bictegravir
- Drug Categories
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals used in combination for the treatment of HIV infections
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Heterocyclic Compounds, Fused-Ring
- Human Immunodeficiency Virus Integrase Strand Transfer Inhibitor
- MATE 1 Inhibitors
- MATE inhibitors
- Pyridines
- UGT1A1 Substrates
- 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
- Chase SP, Freimanis AK: Abdominal echography. Ohio State Med J. 1971 Oct;67(10):901-6. [Article]
- Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1–Infected Adults [Link]
- BICTEGRAVIR [Link]
- FDA APPROVES BIKTARVY [Link]
- BICTEGRAVIR SODIUM [Link]
- FDA Approved Drug Products: BIKTARVY (bictegravir, emtricitabine, and tenofovir alafenamide) tablets, for oral use [Link]
- External Links
- PubChem Compound
- 90311989
- PubChem Substance
- 347828148
- ChemSpider
- 44208822
- BindingDB
- 330048
- 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
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Human Immunodeficiency Virus Type 1 (HIV-1) Infection 1 4 Completed Basic Science ART / Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Prevention HIV, Prevention 1 4 Completed Treatment Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Treatment Human Immunodeficiency Virus Type 1 (HIV-1) Infection 2 4 Enrolling by Invitation Treatment Human Immunodeficiency Virus Type 1 (HIV-1) Infection 1 4 Not Yet Recruiting Treatment Coronary Artery Disease (CAD) / Human Immunodeficiency Virus (HIV) Infections 1 4 Not Yet Recruiting Treatment HIV-infected Patient Kidney Transplant Recipient 1 4 Not Yet Recruiting Treatment Human Immunodeficiency Virus (HIV) Infections 3 4 Not Yet Recruiting Treatment Human Immunodeficiency Virus Type 1 (HIV-1) Infection 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet, film coated Oral Tablet, coated Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6642245 Yes 2003-11-04 2021-05-04 US US6703396 Yes 2004-03-09 2021-09-09 US US9296769 Yes 2016-03-29 2033-02-15 US US7803788 No 2010-09-28 2022-02-02 US US8754065 Yes 2014-06-17 2033-02-15 US US7390791 Yes 2008-06-24 2025-10-17 US US9216996 No 2015-12-22 2033-12-19 US US9708342 No 2017-07-18 2035-06-19 US US9732092 No 2017-08-15 2033-12-19 US US10385067 No 2019-08-20 2035-06-19 US US10548846 No 2020-02-04 2036-11-08 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source boiling point (°C) 682.5±55.0 °C at 760 mmHg [L1221] - Predicted Properties
Property Value Source Water Solubility 0.0537 mg/mL ALOGPS logP 1.28 ALOGPS logP 1.36 ChemAxon logS -3.9 ALOGPS pKa (Strongest Acidic) 9.81 ChemAxon pKa (Strongest Basic) -0.3 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 6 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 99.18 Å2 ChemAxon Rotatable Bond Count 3 ChemAxon Refractivity 105.44 m3·mol-1 ChemAxon Polarizability 41.14 Å3 ChemAxon Number of Rings 5 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 Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- 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
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
- Biktarvy FDA label [File]
Drug created at October 20, 2016 20:49 / Updated at February 03, 2022 21:01