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Identification
NameAtazanavir
Accession NumberDB01072  (APRD00804)
Typesmall molecule
Groupsapproved, investigational
Description

Atazanavir (formerly known as BMS-232632) is an antiretroviral drug of the protease inhibitor (PI) class. Like other antiretrovirals, it is used to treat infection of human immunodeficiency virus (HIV). Atazanavir is distinguished from other PIs in that it can be given once-daily (rather than requiring multiple doses per day) and has lesser effects on the patient’s lipid profile (the amounts of cholesterol and other fatty substances in the blood). Like other protease inhibitors, it is used only in combination with other HIV medications. The U.S. Food and Drug Administration (FDA) approved atazanavir on June 20, 2003. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
ATVNot AvailableNot Available
ATZNot AvailableNot Available
Salts
Name/CAS Structure Properties
Atazanavir sulfate
229975-97-7
Thumb
  • InChI Key: DQSGVVGOPRWTKI-QVFAWCHISA-N
  • Monoisotopic Mass: 802.35712729
  • Average Mass: 802.934
DBSALT000426
Brand names
NameCompany
LatazanavirNot Available
ReyatazNot Available
ZrivadaNot Available
Brand mixturesNot Available
Categories
CAS number198904-31-3
WeightAverage: 704.8555
Monoisotopic: 704.389748048
Chemical FormulaC38H52N6O7
InChI KeyAXRYRYVKAWYZBR-GASGPIRDSA-N
InChI
InChI=1S/C38H52N6O7/c1-37(2,3)31(41-35(48)50-7)33(46)40-29(22-25-14-10-9-11-15-25)30(45)24-44(43-34(47)32(38(4,5)6)42-36(49)51-8)23-26-17-19-27(20-18-26)28-16-12-13-21-39-28/h9-21,29-32,45H,22-24H2,1-8H3,(H,40,46)(H,41,48)(H,42,49)(H,43,47)/t29-,30-,31+,32+/m0/s1
IUPAC Name
methyl N-[(1S)-1-{N'-[(2S,3S)-2-hydroxy-3-[(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethylbutanamido]-4-phenylbutyl]-N'-{[4-(pyridin-2-yl)phenyl]methyl}hydrazinecarbonyl}-2,2-dimethylpropyl]carbamate
SMILES
COC(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)[C@@H](O)CN(CC1=CC=C(C=C1)C1=CC=CC=N1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C(C)(C)C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentN-acyl-alpha Amino Acids and Derivatives
Alternative parentsAlpha Amino Acid Amides; Phenylpyridines; Amphetamines and Derivatives; Dicarboxylic Acids and Derivatives; Secondary Carboxylic Acid Amides; Secondary Alcohols; Carbamic Acids and Derivatives; Carboxylic Acid Hydrazides; Carboxylic Acids; Polyamines; Ethers; Enolates; Hydrazines and Derivatives
Substituentsamphetamine or derivative; pyridine; dicarboxylic acid derivative; benzene; carboxamide group; carbamic acid derivative; secondary carboxylic acid amide; secondary alcohol; carboxylic acid hydrazide; enolate; carboxylic acid; ether; polyamine; hydrazine derivative; alcohol; amine; organonitrogen compound
Classification descriptionThis compound belongs to the n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at his terminal nitrogen atom.
Pharmacology
IndicationUsed in combination with other antiretroviral agents for the treatment of HIV-1 infection, as well as postexposure prophylaxis of HIV infection in individuals who have had occupational or nonoccupational exposure to potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.
PharmacodynamicsAtazanavir (ATV) is an azapeptide HIV-1 protease inhibitor (PI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Atazanavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. Atazanivir is pharmacologically related but structurally different from other protease inhibitors and other currently available antiretrovirals.
Mechanism of actionAtazanavir selectively inhibits the virus-specific processing of viral Gag and Gag-Pol polyproteins in HIV-1 infected cells by binding to the active site of HIV-1 protease, thus preventing the formation of mature virions. Atazanavir is not active against HIV-2.
AbsorptionAtazanavir is rapidly absorbed with a Tmax of approximately 2.5 hours. Administration of atazanavir with food enhances bioavailability and reduces pharmacokinetic variability. Oral bioavailability is 60-68%.
Volume of distributionNot Available
Protein binding86% bound to human serum proteins (alpha-1-acid glycoprotein and albumin). Protein binding is independent of concentration.
Metabolism

Atazanavir is extensively metabolized in humans, primarily by the liver. The major biotransformation pathways of atazanavir in humans consisted of monooxygenation and dioxygenation. Other minor biotransformation pathways for atazanavir or its metabolites consisted of glucuronidation, N-dealkylation, hydrolysis, and oxygenation with dehydrogenation. In vitro studies using human liver microsomes suggested that atazanavir is metabolized by CYP3A.

Route of eliminationNot Available
Half lifeElimination half-life in adults (healthy and HIV infected) is approximately 7 hours (following a 400 mg daily dose with a light meal). Elimination half-life in hepatically impaired is 12.1 hours (following a single 400 mg dose).
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Human Immunodeficiency Virus
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.7997
Blood Brain Barrier - 0.9409
Caco-2 permeable - 0.7017
P-glycoprotein substrate Substrate 0.832
P-glycoprotein inhibitor I Inhibitor 0.81
P-glycoprotein inhibitor II Non-inhibitor 0.844
Renal organic cation transporter Non-inhibitor 0.924
CYP450 2C9 substrate Non-substrate 0.7898
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.6463
CYP450 1A2 substrate Non-inhibitor 0.7553
CYP450 2C9 substrate Non-inhibitor 0.7041
CYP450 2D6 substrate Non-inhibitor 0.848
CYP450 2C19 substrate Non-inhibitor 0.5948
CYP450 3A4 substrate Non-inhibitor 0.8425
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7718
Ames test Non AMES toxic 0.6714
Carcinogenicity Non-carcinogens 0.7261
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.7082 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9766
hERG inhibition (predictor II) Inhibitor 0.6538
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb co
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
Prices
Unit descriptionCostUnit
Reyataz 300 mg capsule36.63USDcapsule
Reyataz 150 mg capsule18.49USDcapsule
Reyataz 200 mg capsule18.49USDcapsule
Reyataz 100 mg capsule18.12USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States60873831998-12-212018-12-21
United States58499111997-06-202017-06-20
Canada22508402006-07-042017-04-14
Canada23177362004-11-022018-12-22
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilityFree base slightly soluble (4-5 mg/mL)Not Available
logP4.5Not Available
Predicted Properties
PropertyValueSource
water solubility3.27e-03 g/lALOGPS
logP4.08ALOGPS
logP4.54ChemAxon
logS-5.3ALOGPS
pKa (strongest acidic)11.92ChemAxon
pKa (strongest basic)4.42ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count7ChemAxon
hydrogen donor count5ChemAxon
polar surface area171.22ChemAxon
rotatable bond count18ChemAxon
refractivity191.8ChemAxon
polarizability76.83ChemAxon
number of rings3ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US5849911
General Reference
  1. Croom KF, Dhillon S, Keam SJ: Atazanavir: a review of its use in the management of HIV-1 infection. Drugs. 2009 May 29;69(8):1107-40. doi: 10.2165/00003495-200969080-00009. Pubmed
  2. von Hentig N: Atazanavir/ritonavir: a review of its use in HIV therapy. Drugs Today (Barc). 2008 Feb;44(2):103-32. Pubmed
  3. Swainston Harrison T, Scott LJ: Atazanavir: a review of its use in the management of HIV infection. Drugs. 2005;65(16):2309-36. Pubmed
  4. Le Tiec C, Barrail A, Goujard C, Taburet AM: Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035-50. Pubmed
  5. Lopez-Cortes LF: [Pharmacology, pharmacokinetic features and interactions of atazanavir] Enferm Infecc Microbiol Clin. 2008 Dec;26 Suppl 17:2-8. Pubmed
  6. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. Pubmed
External Links
ResourceLink
KEGG DrugD01276
PubChem Compound148192
PubChem Substance46508504
ChemSpider130642
BindingDB13934
ChEBI37924
ChEMBLCHEMBL1163
Therapeutic Targets DatabaseDNC000332
PharmGKBPA10251
Drug Product Database2248610
RxListhttp://www.rxlist.com/cgi/generic/reyataz.htm
Drugs.comhttp://www.drugs.com/cdi/atazanavir.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/rey1671.shtml
WikipediaAtazanavir
ATC CodesJ05AE08
AHFS Codes
  • 08:18.08.08
PDB EntriesNot Available
FDA labelshow(412 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbacavirThe serum concentration of Abacavir may be decreased by protease inhibitors such as Atazanavir. The antiviral response should be closely monitored.
AbirateroneStrong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
AcenocoumarolThe protease inhibitor, atazanavir, may increase the anticoagulant effect of acenocoumarol.
AluminiumThis gastric pH modifier decreases the levels/effects of atazanavir
AmiodaroneIncreased risk of cardiotoxicity and arrhythmias.
AmitriptylineAtazanavir may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if atazanavir if initiated, discontinued or dose changed.
AmoxapineAtazanavir may increase the effect and toxicity of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if atazanavir if initiated, discontinued or dose changed.
AnisindioneThe protease inhibitor, atazanavir, may increase the anticoagulant effect of anisindione.
AtorvastatinAtazanavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
BepridilAtazanavir may increase the effect and toxicity of bepridil.
Bismuth SubsalicylateThis gastric pH modifier decreases the levels/effects of atazanavir
BromazepamAtazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if atazanavir is initiated, discontinued or dose changed. Dosage adjustments may be required.
BuprenorphineAtazanavir may increase the serum concentration of Buprenorphine. Buprenorphine may decrease the serum concentration of Atazanavir. Avoid use of buprenorphine in patients receiving atazanavir without ritonavir boosting due to possible decreases in atazanavir exposure. In patients receiving buprenorphine with atazanavir/ritonavir, monitor for increased buprenorphine effects and consider dose reductions if patients experience adverse effects.
CabazitaxelConcomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
CalciumThis gastric pH modifier decreases the levels/effects of atazanavir
CimetidineThis gastric pH modifier decreases the levels/effects of atazanavir
CisaprideIncreased risk of cardiotoxicity and arrhythmias
ClarithromycinAtazanavir may increase serum level of clarithromycin.
ClomipramineAtazanavir may increase the effect and toxicity of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if atazanavir is initiated, discontinued or dose changed.
CyclosporineAtazanavir may increase the therapeutic and adverse effects of cyclosporine.
DantroleneAtazanavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if atazanavir is initiated, discontinued or dose changed.
DesipramineAtazanavir may increase the effect and toxicity of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if atazanavir is initiated, discontinued or dose changed.
DicoumarolThe protease inhibitor, atazanavir, may increase the anticoagulant effect of dicumarol.
DihydroergotamineAtazanavir may increase the therapeutic and adverse effects of dihydroergotamine.
Dihydroquinidine barbiturateIncreased risk of cardiotoxicity and arrhythmias
DihydroxyaluminiumThis gastric pH modifier decreases the levels/effects of atazanavir
DiltiazemAtazanavir may increase the therapeutic and adverse effects of diltiazem resulting in increased risk of AV block. Consider alternate therapy, a 50% dose reduction of diltiazem and monitor for changes in the therapeutic and adverse effects of diltiazem if atazanavir is initiated, discontinued or dose changed.
DoxepinAtazanavir may increase the effect and toxicity of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if atazanavir if initiated, discontinued or dose changed.
EfavirenzEfavirenz decreases the levels/effects of atazanavir
EltrombopagDecreases metabolism, will increase effect/level of eltrombopag. UDP-glucuronosyltransferase inhibition.
ErgotamineAtazanavir may increase the effect and toxicity of ergotamine.
ErlotinibThis CYP3A4 inhibitor increases levels/toxicity of erlotinib
EsomeprazoleThis gastric pH modifier decreases the levels/effects of atazanavir
EtravirineAtazanavir, when administered concomitantly with etravirine, may experience a decrease in serum concentrations. Etravirine, when administered concomitantly with Atazanavir, may expereince an increase in serum concentrations. Recommended to avoid use of this combination.
FamotidineThis gastric pH modifier decreases the levels/effects of atazanavir
ImipramineAtazanavir may increase the effect and toxicity of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if atazanavir if initiated, discontinued or dose changed.
IndinavirIncreased risk of hyperbilirubinemia with this association
IrinotecanIncreases levels/effect of irinotecan
LansoprazoleThis gastric pH modifier decreases the levels/effects of atazanavir
LidocaineIncreased risk of cardiotoxicity and arrhythmias
LovastatinAtazanavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
LurasidoneConcomitant therapy with a strong CYP3A4 inhibitor will increase level or effect of lurasidone. Coadministration with lurasidone is contraindicated.
MagnesiumThis gastric pH modifier decreases the levels/effects of atazanavir
Magnesium oxideThis gastric pH modifier decreases the levels/effects of atazanavir
Magnesium SulfateThis gastric pH modifier decreases the levels/effects of atazanavir
MethylergometrineIncreases the effect and toxicity of ergot derivative
MidazolamAtazanavir may increase the effect and toxicity of the benzodiazepine, midazolam.
NevirapineNevirapine, a strong CYP3A4 inducer, may decrease the serum concentration of atazanavir by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atazanavir if nevirapine is initiated, discontinued or dose changed.
NizatidineThis gastric pH modifier decreases the levels/effects of atazanavir
NortriptylineAtazanavir may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if atazanavir if initiated, discontinued or dose changed.
OmeprazoleThis gastric pH modifier decreases the levels/effects of atazanavir
PantoprazoleThis gastric pH modifier decreases the levels/effects of atazanavir
PimozideThe protease inhibitor, atazanavir, may increase the effect and toxicity of pimozide.
PitavastatinIncreases serum concentration of pitavastatin and the potential for adverse drug reactions. Avoid concomitant drug therapy.
ProtriptylineAtazanavir may increase the effect and toxicity of the tricyclic antidepressant, protriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of protriptyline if atazanavir if initiated, discontinued or dose changed.
QuinidineIncreased risk of cardiotoxicity and arrhythmias.
Quinidine barbiturateIncreased risk of cardiotoxicity and arrhythmias
RabeprazoleRabeprazole may decrease the serum levels and therapeutic effects of atazanavir.
RamelteonAtazanavir increases levels/toxicity of ramelteon
RanitidineRanitidine may decrease the levels/effects of atazanavir.
RanolazineAtazanavir, a strong CYP3A4 inhibitor, may increase the serum level of ranolazine. Concomitant therapy is contraindicated.
RifabutinAtazanavir may increase levels/toxicity of rifabutin.
RifampicinRifampin reduces levels and efficacy of atazanavir
RitonavirAssociation with dose adjustment
SildenafilIncreases the effect and toxicity of sildenafil
SimvastatinIncreased risk of myopathy/rhabdomyolysis
SirolimusIncreases the effect and toxicity of immunosuppressant
Sodium bicarbonateThis gastric pH modifier decreases the levels/effect of atazanavir
St. John's WortSt. John's Wort decreases the levels/effects of atazanavir
SunitinibPossible increase in sunitinib levels
TacrolimusThe protease inhibitor, Atazanavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Atazanavir therapy is initiated, discontinued or altered.
TadalafilAtazanavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
TamoxifenAtazanavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
TamsulosinAtazanvir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Atazanavir is initiated, discontinued, or dose changed.
TelithromycinCo-administration may result in altered plasma concentrations of Atazanavir and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.
TemsirolimusAtazanavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
TeniposideThe strong CYP3A4 inhibitor, Atazanavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Atazanavir is initiated, discontinued or dose changed.
TenofovirConcomitant therapy may result in decreased serum levels of Atazanavir and increased levels of Tenofovir. Concomitant therapy should only be used with the inclusion of Ritonavir.
TiagabineThe strong CYP3A4 inhibitor, Atazanavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Atazanavir is initiated, discontinued or dose changed.
TipranavirTipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Atazanavir. Consider alternate therapy.
TolterodineAtazanavir may decrease the metabolism and clearance of Tolterodine. Adjust the Tolterodine dose and monitor for efficacy and toxicity.
TramadolAtazanavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
TrazodoneThe protease inhibitor, Atazanavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Atazanavir is initiated, discontinued or dose changed.
TretinoinThe strong CYP2C8 inhibitor, Atazanavir, may decrease the metabolism and clearance of oral Tretinoin. Consider alternate therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Atazanavir is initiated, discontinued to dose changed.
TriazolamAtazanavir may increase the effect and toxicity of the benzodiazepine, triazolam.
TrimipramineThe strong CYP3A4 inhibitor, Atazanavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Atazanavir is initiated, discontinued or dose changed.
VardenafilAtazanavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
VemurafenibStrong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
VenlafaxineAtazanavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Atazanavir is initiated, discontinued, or dose changed.
VerapamilAtazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Atazanavir is initiated, discontinued or dose changed.
VilazodoneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. imit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors.
VinblastineAtazanavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Atazanavir is initiated, discontinued or dose changed.
VincristineAtazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Atazanavir is initiated, discontinued or dose changed.
VinorelbineAtazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Atazanavir is initiated, discontinued or dose changed.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of atazanavir by decreasing its metabolism. The serum concentration of voriconazole may be increased by atazanavir. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
WarfarinThe protease inhibitor, atazanavir, may increase the anticoagulant effect of warfarin.
ZolpidemAtazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if atazanavir is initiated, discontinued or dose changed.
ZonisamideAtazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if atazanavir is initiated, discontinued or dose changed.
ZopicloneAtazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if atazanavir is initiated, discontinued or dose changed.
Food Interactions
  • Administration with food reduces pharmacokinetic variability.
  • Food increases product absorption.

Targets

1. Protease

Kind: protein

Organism: Human immunodeficiency virus 1

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
HIV-1 Protease Q72874 Details

References:

  1. Dierynck I, De Wit M, Gustin E, Keuleers I, Vandersmissen J, Hallenberger S, Hertogs K: Binding kinetics of darunavir to HIV-1 protease explain the potent antiviral activity and high genetic barrier. J Virol. 2007 Oct 10;. Pubmed
  2. Dandache S, Sevigny G, Yelle J, Stranix BR, Parkin N, Schapiro JM, Wainberg MA, Wu JJ: In Vitro Antiviral Activity and Cross-Resistance Profile of PL-100, a Next Generation Protease Inhibitor of Human Immunodeficiency Virus Type 1. Antimicrob Agents Chemother. 2007 Jul 16;. Pubmed
  3. Wood R: Atazanavir: its role in HIV treatment. Expert Rev Anti Infect Ther. 2008 Dec;6(6):785-96. Pubmed
  4. Le Tiec C, Barrail A, Goujard C, Taburet AM: Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035-50. Pubmed
  5. Pyrko P, Kardosh A, Wang W, Xiong W, Schonthal AH, Chen TC: HIV-1 protease inhibitors nelfinavir and atazanavir induce malignant glioma death by triggering endoplasmic reticulum stress. Cancer Res. 2007 Nov 15;67(22):10920-8. Pubmed
  6. Menendez-Arias L, Tozser J: HIV-1 protease inhibitors: effects on HIV-2 replication and resistance. Trends Pharmacol Sci. 2008 Jan;29(1):42-9. Epub 2007 Dec 4. Pubmed
  7. Lopez-Cortes LF: [Pharmacology, pharmacokinetic features and interactions of atazanavir] Enferm Infecc Microbiol Clin. 2008 Dec;26 Suppl 17:2-8. Pubmed
  8. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. Pubmed
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Le Tiec C, Barrail A, Goujard C, Taburet AM: Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035-50. Pubmed
  2. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. Pubmed
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

2. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Perloff ES, Duan SX, Skolnik PR, Greenblatt DJ, von Moltke LL: Atazanavir: effects on P-glycoprotein transport and CYP3A metabolism in vitro. Drug Metab Dispos. 2005 Jun;33(6):764-70. Epub 2005 Mar 11. Pubmed
  2. Lucia MB, Golotta C, Rutella S, Rastrelli E, Savarino A, Cauda R: Atazanavir inhibits P-glycoprotein and multidrug resistance-associated protein efflux activity. J Acquir Immune Defic Syndr. 2005 Aug 15;39(5):635-7. Pubmed
  3. Chinn LW, Gow JM, Tse MM, Becker SL, Kroetz DL: Interindividual variability in the effect of atazanavir and saquinavir on the expression of lymphocyte P-glycoprotein. J Antimicrob Chemother. 2007 Jul;60(1):61-7. Epub 2007 May 17. Pubmed
  4. Wood R: Atazanavir: its role in HIV treatment. Expert Rev Anti Infect Ther. 2008 Dec;6(6):785-96. Pubmed
  5. Janneh O, Anwar T, Jungbauer C, Kopp S, Khoo SH, Back DJ, Chiba P: P-glycoprotein, multidrug resistance-associated proteins and human organic anion transporting polypeptide influence the intracellular accumulation of atazanavir. Antivir Ther. 2009;14(7):965-74. Pubmed
  6. Storch CH, Theile D, Lindenmaier H, Haefeli WE, Weiss J: Comparison of the inhibitory activity of anti-HIV drugs on P-glycoprotein. Biochem Pharmacol. 2007 May 15;73(10):1573-81. Epub 2007 Jan 24. Pubmed

2. Multidrug resistance-associated protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 1 P33527 Details

References:

  1. Janneh O, Anwar T, Jungbauer C, Kopp S, Khoo SH, Back DJ, Chiba P: P-glycoprotein, multidrug resistance-associated proteins and human organic anion transporting polypeptide influence the intracellular accumulation of atazanavir. Antivir Ther. 2009;14(7):965-74. Pubmed
  2. Lucia MB, Golotta C, Rutella S, Rastrelli E, Savarino A, Cauda R: Atazanavir inhibits P-glycoprotein and multidrug resistance-associated protein efflux activity. J Acquir Immune Defic Syndr. 2005 Aug 15;39(5):635-7. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on December 04, 2013 16:12