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Identification
NameItraconazole
Accession NumberDB01167  (APRD00040)
TypeSmall Molecule
GroupsApproved, Investigational
Description

One of the triazole antifungal agents that inhibits cytochrome P-450-dependent enzymes resulting in impairment of ergosterol synthesis. It has been used against histoplasmosis, blastomycosis, cryptococcal meningitis & aspergillosis. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
ItraconazolSpanishNot Available
ItraconazoleNot AvailableNot Available
ItraconazolumLatinNot Available
Itrizole (tn)Not AvailableNot Available
OriconazoleNot AvailableNot Available
Sporanox (tn)Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ItrizoleNot Available
OnmelNot Available
OriconazoleNot Available
SporalNot Available
SporanoxNot Available
Brand mixturesNot Available
Categories
CAS number84625-61-6
WeightAverage: 705.633
Monoisotopic: 704.239307158
Chemical FormulaC35H38Cl2N8O4
InChI KeyVHVPQPYKVGDNFY-ZPGVKDDISA-N
InChI
InChI=1S/C35H38Cl2N8O4/c1-3-25(2)45-34(46)44(24-40-45)29-7-5-27(6-8-29)41-14-16-42(17-15-41)28-9-11-30(12-10-28)47-19-31-20-48-35(49-31,21-43-23-38-22-39-43)32-13-4-26(36)18-33(32)37/h4-13,18,22-25,31H,3,14-17,19-21H2,1-2H3/t25?,31-,35-/m0/s1
IUPAC Name
1-(butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one
SMILES
CCC(C)N1N=CN(C1=O)C1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OC[C@H]2CO[C@@](CN3C=NC=N3)(O2)C2=C(Cl)C=C(Cl)C=C2)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPiperazines
SubclassPhenylpiperazines
Direct parentPhenylpiperazines
Alternative parentsPhenyltriazoles; Dichlorobenzenes; Phenol Ethers; Alkyl Aryl Ethers; Aryl Chlorides; Diazinanes; 1,3-Dioxolanes; Tertiary Amines; Polyamines; Dialkyl Ethers; Acetals; Organochlorides
Substituents1,3-dichlorobenzene; phenol ether; alkyl aryl ether; chlorobenzene; aryl chloride; aryl halide; benzene; 1,4-diazinane; azole; meta-dioxolane; 1,2,4-triazole; tertiary amine; acetal; dialkyl ether; polyamine; ether; amine; organohalogen; organonitrogen compound; organochloride
Classification descriptionThis compound belongs to the phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Pharmacology
IndicationFor the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: pulmonary and extrapulmonary blastomycosis, histoplasmosis, aspergillosis, and onychomycosis.
PharmacodynamicsItraconazole is an imidazole/triazole type antifungal agent. Itraconazole is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation via the inhibition of the enzyme cytochrome P450 14α-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. The subsequent loss of normal sterols correlates with the accumulation of 14 α-methyl sterols in fungi and may be partly responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Itraconazole exhibits in vitro activity against Cryptococcus neoformans and Candida spp. Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans and for systemic infections due to Candida albicans.
Mechanism of actionItraconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Itraconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.
AbsorptionThe absolute oral bioavailability of itraconazole is 55%, and is maximal when taken with a full meal.
Volume of distribution
  • 796 ± 185 L
Protein binding99.8%
Metabolism

Itraconazole is extensively metabolized by the liver into a large number of metabolites, including hydroxyitraconazole, the major metabolite. The main metabolic pathways are oxidative scission of the dioxolane ring, aliphatic oxidation at the 1-methylpropyl substituent, N-dealkylation of this 1-methylpropyl substituent, oxidative degradation of the piperazine ring and triazolone scission.

SubstrateEnzymesProduct
Itraconazole
hydroxyitraconazoleDetails
Route of eliminationItraconazole is metabolized predominately by the cytochrome P450 3A4 isoenzyme system (CYP3A4) in the liver, resulting in the formation of several metabolites, including hydroxyitraconazole, the major metabolite. Fecal excretion of the parent drug varies between 3-18% of the dose. Renal excretion of the parent drug is less than 0.03% of the dose. About 40% of the dose is excreted as inactive metabolites in the urine. No single excreted metabolite represents more than 5% of a dose.
Half life21 hours
Clearance
  • 381 +/- 95 mL/minute [IV administration]
ToxicityNo significant lethality was observed when itraconazole was administered orally to mice and rats at dosage levels of 320 mg/kg or to dogs at 200 mg/kg.
Affected organisms
  • Fungi, yeast and protozoans
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9973
Blood Brain Barrier - 0.6151
Caco-2 permeable + 0.5511
P-glycoprotein substrate Substrate 0.6397
P-glycoprotein inhibitor I Inhibitor 0.7973
P-glycoprotein inhibitor II Non-inhibitor 0.88
Renal organic cation transporter Non-inhibitor 0.7497
CYP450 2C9 substrate Non-substrate 0.8116
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.7408
CYP450 1A2 substrate Non-inhibitor 0.7666
CYP450 2C9 substrate Inhibitor 0.618
CYP450 2D6 substrate Non-inhibitor 0.8622
CYP450 2C19 substrate Inhibitor 0.5703
CYP450 3A4 substrate Inhibitor 0.5279
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8219
Ames test AMES toxic 0.5303
Carcinogenicity Non-carcinogens 0.7478
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 3.3118 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.5782
hERG inhibition (predictor II) Inhibitor 0.6096
Pharmacoeconomics
Manufacturers
  • Sandoz inc
  • Ortho mcneil janssen pharmaceuticals inc
  • Stiefel laboratories inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
LiquidOral
Prices
Unit descriptionCostUnit
Itraconazole 28 100 mg capsule Disp Pack270.89USDdisp
Itraconazole powder32.13USDg
Sporanox 100 mg capsule12.14USDcapsule
Itraconazole 100 mg capsule9.46USDcapsule
Sporanox 10 mg/ml Solution1.41USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States64070791999-06-182019-06-18
United States56330151994-05-272014-05-27
Canada21428481999-11-162013-08-27
Canada13364981995-08-012012-08-01
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point166.2 °CNot Available
water solubilityInsolubleNot Available
logP5.66HTTP://WWW.RXLIST.COM
pKa3.70Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00964ALOGPS
logP5.48ALOGPS
logP7.31ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)3.92ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area100.79 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity200.4 m3·mol-1ChemAxon
Polarizability74.7 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Jong-Soo Woo, Hong-Gi Yi, “Antifungal oral composition containing itraconazole and process for preparing same.” U.S. Patent US6039981, issued May, 1998.

US6039981
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00350
PubChem Compound55283
PubChem Substance46505954
ChemSpider49927
ChEBI6076
ChEMBLCHEMBL22587
Therapeutic Targets DatabaseDAP000631
PharmGKBPA450132
Drug Product Database2231347
RxListhttp://www.rxlist.com/cgi/generic/itraconazole.htm
Drugs.comhttp://www.drugs.com/cdi/itraconazole.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/spo1411.shtml
WikipediaItraconazole
ATC CodesJ02AC02
AHFS Codes
  • 08:14.08
PDB Entries
FDA labelshow(1.58 MB)
MSDSshow(73.6 KB)
Interactions
Drug Interactions
Drug
AbirateroneStrong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
AcenocoumarolItraconazole may increase the anticoagulant effect of acenocoumarol.
AlfentanilItraconazole may increase the effect and toxicity of alfentanil.
AlfuzosinThe antifungal increases the effect of alfuzosin
AliskirenAvoid combination due to increased serum concentration of aliskiren.
AlmotriptanThis potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
AlprazolamItraconazole may increase the effect of the benzodiazepine, alprazolam.
AluminiumAluminum-containing antacids may decrease the effect of itraconazole.
AnisindioneItraconazole may increase the anticoagulant effect of anisindione.
ApixabanAvoid combination. Otherwise, itraconazole will likely increase apixaban serum concentration.
AprepitantThis CYP3A4 inhibitor, itraconazole, may increase the effect and toxicity of aprepitant.
AripiprazoleItraconazole may increase the effect of aripiprazole.
AstemizoleIncreased risk of cardiotoxicity and arrhythmias
AtorvastatinIncreased risk of myopathy/rhabdomyolysis
BosentanItraconazole may increase the effect and toxicity of bosentan.
BromazepamItraconazole may increase the serum concentration of bromazepam by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of bromazepam if itraconazole is initiated, discontinued or dose changed.
BudesonideItraconazole may increase levels/effect of budesonide.
BusulfanItraconazole reduced busulfan clearance by up to 25% in patients receiving itraconazole compared to those that did not receive it. Concomitant therapy may lead to toxic plasma levels of busulfan.
CabazitaxelConcomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
CalciumCalcium-containing antacids may decrease the effect of itraconazole.
Calcium carbonateThe antacid, calcium carbonate, may decrease the effect of itraconazole by decreasing its absorption.
CarbamazepineItraconazole may increase the effect of carbamazepine.
CeliprololItaconazole increases levels/effect of celiprolol
CerivastatinIncreased risk of myopathy/rhabdomyolysis
ChlordiazepoxideItraconazole may increase the effect of the benzodiazepine, chlordiazepoxide.
CiclesonideIncreased effects/toxicity of ciclesonide
CilostazolItraconazole may increase the effect of cilostazol.
CimetidineThe H2-receptor antagonist, cimetidine, may decrease the absorption of itraconazole.
CinacalcetItraconazole may increase the effect and toxicity of cinacalcet.
CisaprideIncreased risk of cardiotoxicity and arrhythmias
ClarithromycinThe macrolide, clarithromycin, may increase the effect and toxicity of itraconazole.
ClonazepamItraconazole may increase the effect of the benzodiazepine, clonazepam.
ClorazepateItraconazole may increase the effect of the benzodiazepine, clorazepate.
ConivaptanAntifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.
CyclosporineItraconazole may increase the effect of cyclosporine.
DantroleneItraconazole 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 itraconazole is initiated, discontinued or dose changed.
DarifenacinThis potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
DiazepamItraconazole may increase the effect of the benzodiazepine, diazepam.
DicoumarolItraconazole may increase the anticoagulant effect of dicumarol.
DigoxinItraconazole increases the effect of digoxin
DihydroergotaminePossible ergotism and severe ischemia with this combination
DofetilideThis strong CYP3A4 inhibitor increases the effect and toxicity of dofetilide
DronedaroneItraconazole is a strong CYP3A4 inhibitor in which concomitant use with dronedarone will significantly increase its exposure. Avoid concomitant use.
EletriptanThis potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
EplerenoneItraconazole may increase the effect and toxicity of eplerenone.
ErgotaminePossible ergotism and severe ischemia with this combination
ErlotinibItraconazole may decrease the metabolism of erlotinib. Monitor for changes in the therapeutic and adverse effects of erlotinib if itraconazole is initiated, discontinued or dose changed.
ErythromycinThe macrolide, erythromycin, may increase the effect and toxicity of itraconazole.
EsomeprazoleThe proton pump inhibitor, esomeprazole, may decrease the absorption of itraconazole.
EstazolamItraconazole may increase the effect of the benzodiazepine, estazolam.
EthotoinPhenytoin decreases the effect of itraconazole
EverolimusItraconazole may increase everolimus levels/toxicity.
FamotidineThe H2-receptor antagonist, famotidine, may decrease the absorption of itraconazole.
FelodipineItraconazole may increase the therapeutic and adverse effects of felodipine.
FentanylItraconazole may increase levels/toxicity of fentanyl.
FlurazepamItraconazole may increase the effect of the benzodiazepine, flurazepam.
FosphenytoinPhenytoin decreases the effect of itraconazole
GefitinibItraconazole, a strong CYP3A4 inhibitor, may decrease the metabolism of gefitinib. Monitor for changes in the therapeutic and adverse effects of gefitinib if itraconazole is initiated, discontinued or dose changed.
HalazepamItraconazole may increase the effect of the benzodiazepine, halazepam.
HaloperidolItraconazole may increase the effect and toxicity of haloperidol.
ImatinibItraconazole may increase the levels of imatinib.
IvacaftorStrong CYP3A4 inhibitors may increase levels of ivacaftor. Monitor concomitant therapy closely.
JosamycinThe macrolide, josamycin, may increase the effect and toxicity of itraconazole.
LansoprazoleThe proton pump inhibitor, lansoprazole, may decrease the absorption of itraconazole.
Levomethadyl AcetateItraconazole increases the effect/toxicity of levomethadyl
LovastatinIncreased risk of myopathy/rhabdomyolysis
LurasidoneConcomitant therapy with a strong CYP3A4 inhibitor will increase level or effect of lurasidone. Coadministration with lurasidone is contraindicated.
Magnesium oxideThe antacid, magnesium oxide, may decrease the effect of itraconazole by decreasing its absorption.
MephenytoinPhenytoin decreases the effect of itraconazole
MestranolThis anti-infectious agent could decrease the effect of the oral contraceptive
MethylprednisoloneThe imidazole, itraconazole, may increase the effect and toxicity of the corticosteroid, methylprednisolone.
MidazolamItraconazole may increase the effect of the benzodiazepine, midazolam.
NizatidineThe H2-receptor antagonist, nizatidine, may decrease the absorption of itraconazole.
OmeprazoleThe proton pump inhibitor, omeprazole, may decrease the absorption of itraconazole.
PantoprazoleThe proton pump inhibitor, pantoprazole, may decrease the absorption of itraconazole.
PazopanibAffects CYP3A4 metabolism therefore will decrease levels or effect of pazopanib. Consider alternate therapy.
PhenobarbitalThe barbiturate, phenobarbital, decreases the effect of itraconazole.
PhenytoinPhenytoin decreases the effect of itraconazole
PimozideIncreased risk of cardiotoxicity and arrhythmias
PonatinibStrong CYP3A4 inhibitors may increase levels of ponatinib. Monitor concomitant therapy closely.
PrednisoloneThe imidazole, itraconazole, may increase the effect and toxicity of the corticosteroid, prednisolone.
PrednisoneThe imidazole, itraconazole, may increase the effect and toxicity of the corticosteroid, prednisone.
QuazepamItraconazole may increase the effect of the benzodiazepine, quazepam.
QuinidineItraconazole may increase the effect and toxicity of quinidine.
Quinidine barbiturateItraconazole may increase the effect and toxicity of quinidine barbiturate.
RabeprazoleThe proton pump inhibitor, rabeprazole, may decrease the absorption of itraconazole.
RanitidineThe H2-receptor antagonist, ranitidine, may decrease the absorption of itraconazole.
RanolazineIncreased levels of ranolazine - risk of toxicity
RegorafenibStrong CYP3A4 inhibitors may increase levels of regorafenib.
RifabutinRifabutin decreases the effect of itraconazole
RifampicinRifampin may decrease the effect of itraconazole.
RisperidoneIncreases the level of risperidone
RitonavirItraconazole may increase the effect and toxicity of ritonavir.
RivaroxabanUse of rivaroxaban with agents that are strong inhibitors of both CYP3A4 and P-glycoproteins are contraindicated.
RuxolitinibStrong CYP3A4 inhibitors may increase levels of ruxolitinib. Consider alternate therapy.
SildenafilItraconazole may increase the effect and toxicity of sildenafil.
SilodosinStrong CYP3A4 inhibitors may increase levels of silodosin. Concomitant administration is contraindicated.
SimvastatinIncreased risk of myopathy/rhabdomyolysis
SirolimusItraconazole may increase the effect and toxicity of sirolimus.
SolifenacinThis potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
SucralfateSucralfate may decrease the absorption of itraconazole.
SunitinibPossible increase in sunitinib levels
TacrolimusThe antifungal, Itraconazole, may increase serum concentrations of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Itraconazole therapy is initiated, discontinued or altered.
TadalafilItraconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
TamoxifenItraconazole may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
TamsulosinItraconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Itraconazole is initiated, discontinued, or dose changed.
TelithromycinItraconazole may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.
TemsirolimusItraconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
TeniposideThe strong CYP3A4 inhibitor, Itraconazole, 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 Itraconazole is initiated, discontinued or dose changed.
TerfenadineIncreased risk of cardiotoxicity and arrhythmias
TiagabineThe strong CYP3A4 inhibitor, Itraconazole, 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 Itraconazole is initiated, discontinued or dose changed.
TipranavirTipranavir may increase the serum concentration of Itraconazole.
TolterodineItraconazole may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
TolvaptanItraconazole is a strong inhibitor of CYP3A4 and will increase serum concentrations of tolvaptan.
TopotecanThe p-glycoprotein inhibitor, Itraconazole, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
TramadolItraconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
TrazodoneThe CYP3A4 inhibitor, Itraconazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Itraconazole is initiated, discontinued or dose changed.
TriazolamItraconazole may increase the effect of the benzodiazepine, triazolam.
TrimipramineThe strong CYP3A4 inhibitor, Itraconazole, 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 Itraconazole is initiated, discontinued or dose changed.
UlipristalConcomitant therapy with strong CYP3A4 inhibitors may increase plasma concentrations of ulipristal. Avoid combination therapy.
VardenafilItraconazole, a potent CYP3A4 inhibitor, may decrease the metabolism and clearance of Vardenafil. Concomitant therapy is contraindicated.
VemurafenibStrong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
VenlafaxineItraconaole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Itraconazole is initiated, discontinued, or dose changed.
VerapamilItraconazole, 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 Itraconazole is initiated, discontinued or dose changed.
VinblastineItraconazole, 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 Itraconazole is initiated, discontinued or dose changed.
VincristineItraconazole, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Itraconazole is initiated, discontinued or dose changed.
VinorelbineItraconazole, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism and/or increasing its efflux. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Itraconazole is initiated, discontinued or dose changed.
WarfarinItraconazole may increase the anticoagulant effect of warfarin by decreasing its metabolism.
ZolpidemItraconazole, 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 itraconazole is initiated, discontinued or dose changed.
ZonisamideItraconazole, 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 itraconazole is initiated, discontinued or dose changed.
ZopicloneItraconazole, 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 itraconzole is initiated, discontinued or dose changed.
Food Interactions
  • Avoid milk, calcium containing dairy products, iron, antacids, or aluminum salts 2 hours before or 6 hours after using antacids while on this medication.
  • Avoid taking with grapefruit juice.
  • Take after a full meal.
  • Take with food.

Targets

1. Lanosterol 14-alpha demethylase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Lanosterol 14-alpha demethylase Q16850 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Cotrim PC, Garrity LK, Beverley SM: Isolation of genes mediating resistance to inhibitors of nucleoside and ergosterol metabolism in Leishmania by overexpression/selection. J Biol Chem. 1999 Dec 31;274(53):37723-30. Pubmed
  3. Carrillo-Munoz AJ, Giusiano G, Ezkurra PA, Quindos G: Antifungal agents: mode of action in yeast cells. Rev Esp Quimioter. 2006 Jun;19(2):130-9. Pubmed

2. Lanosterol 14-alpha demethylase

Kind: protein

Organism: Yeast

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Lanosterol 14-alpha demethylase P50859 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Gachotte D, Pierson CA, Lees ND, Barbuch R, Koegel C, Bard M: A yeast sterol auxotroph (erg25) is rescued by addition of azole antifungals and reduced levels of heme. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11173-8. Pubmed
  4. Henry KW, Nickels JT, Edlind TD: Upregulation of ERG genes in Candida species by azoles and other sterol biosynthesis inhibitors. Antimicrob Agents Chemother. 2000 Oct;44(10):2693-700. Pubmed
  5. Morales IJ, Vohra PK, Puri V, Kottom TJ, Limper AH, Thomas CF Jr: Characterization of a lanosterol 14 alpha-demethylase from Pneumocystis carinii. Am J Respir Cell Mol Biol. 2003 Aug;29(2):232-8. Epub 2003 Feb 26. Pubmed

Enzymes

1. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

2. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. 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. Niwa T, Shiraga T, Takagi A: Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes. Biol Pharm Bull. 2005 Sep;28(9):1805-8. Pubmed
  2. Sakaeda T, Iwaki K, Kakumoto M, Nishikawa M, Niwa T, Jin JS, Nakamura T, Nishiguchi K, Okamura N, Okumura K: Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs. J Pharm Pharmacol. 2005 Jun;57(6):759-64. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  5. Dresser GK, Spence JD, Bailey DG: Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000 Jan;38(1):41-57. Pubmed

4. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

References:

  1. Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. Pubmed

6. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
  2. Wang EJ, Lew K, Casciano CN, Clement RP, Johnson WW: Interaction of common azole antifungals with P glycoprotein. Antimicrob Agents Chemother. 2002 Jan;46(1):160-5. Pubmed
  3. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. Pubmed
  4. Takara K, Tanigawara Y, Komada F, Nishiguchi K, Sakaeda T, Okumura K: Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull. 1999 Dec;22(12):1355-9. Pubmed
  5. Masuda S, Inui K: [Molecular mechanisms on drug transporters in the drug absorption and disposition] Nippon Rinsho. 2002 Jan;60(1):65-73. Pubmed
  6. Lilja JJ, Backman JT, Laitila J, Luurila H, Neuvonen PJ: Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol. Clin Pharmacol Ther. 2003 Mar;73(3):192-8. Pubmed
  7. Sakaeda T, Iwaki K, Kakumoto M, Nishikawa M, Niwa T, Jin JS, Nakamura T, Nishiguchi K, Okamura N, Okumura K: Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs. J Pharm Pharmacol. 2005 Jun;57(6):759-64. Pubmed
  8. Saito M, Hirata-Koizumi M, Miyake S, Hasegawa R: Comparison of information on the pharmacokinetic interactions of Ca antagonists in the package inserts from three countries (Japan, USA and UK). Eur J Clin Pharmacol. 2005 Aug;61(7):531-6. Epub 2005 Jul 23. Pubmed
  9. Shon JH, Yoon YR, Hong WS, Nguyen PM, Lee SS, Choi YG, Cha IJ, Shin JG: Effect of itraconazole on the pharmacokinetics and pharmacodynamics of fexofenadine in relation to the MDR1 genetic polymorphism. Clin Pharmacol Ther. 2005 Aug;78(2):191-201. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on February 04, 2014 21:35