QuickView for Itraconazole (compound)

Summary
General Info

PubChem

PubChem Compound 3793

Name:	Itraconazole
PubChem Compound ID:	3793
Description:	A triazole antifungal agent that inhibits cytochrome P-450-dependent enzymes required for ERGOSTEROL synthesis.
Molecular formula:	C₃₅H₃₈Cl₂N₈O₄
Molecular weight:	705.633 g/mol
Synonyms:	LS-1843; MLS000028582; SMR000058959; Itraconazole

DrugBank

Identification

Name:	Itraconazole
Name (isomeric):	DB01167
Drug Type:	small molecule
Description:	A triazole antifungal agent that inhibits cytochrome P-450-dependent enzymes required for ERGOSTEROL synthesis.
Synonyms:	ITCZ; Itraconazolum [Latin]; Itraconazol [Spanish]; ITR; ITC; ITZ
Brand:	Sporal, Oriconazole, Triasporn, Hyphanox, Itrizole, Sporanox, Sporonox, Sporanos
Category:	Antiprotozoal Agents, Antifungal Agents, Antiprotozoals, Antifungals
CAS number:	84625-61-6

Pharmacology

Indication:	For the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: pulmonary and extrapulmonary blastomycosis, histoplasmosis, aspergillosis, and onychomycosis.
Pharmacology:	Itraconazole 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 lo... show more » Itraconazole 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. show less «
Mechanism of Action:	Itraconazole 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 respir... show more » Itraconazole 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. show less «
Absorption:	The absolute oral bioavailability of itraconazole is 55%, and is maximal when taken with a full meal.
Protein binding:	99.8%
Biotransformation:	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.
Route of elimination:	Itraconazole 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 Life:	21 hours
Clearance:	381 +/- 95 mL/minute [IV administration]
Toxicity:	No 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

Interactions

Food interaction:

Avoid taking with grapefruit juice.

Avoid milk, calcium containing dairy products, iron, antacids, or aluminum salts 2 hours before or 6 hours after using antacids while on this medication.

Take after a full meal.

Take with food.

Drug interaction:

Omeprazole	The proton pump inhibitor, omeprazole, may decrease the absorption of itraconazole.
Clorazepate	Itraconazole may increase the effect of the benzodiazepine, clorazepate.
Tiagabine	The 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.
Prednisolone	The imidazole, itraconazole, may increase the effect and toxicity of the corticosteroid, prednisolone.
Conivaptan	Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.

Omeprazole	The proton pump inhibitor, omeprazole, may decrease the absorption of itraconazole.
Clorazepate	Itraconazole may increase the effect of the benzodiazepine, clorazepate.
Tiagabine	The 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.
Prednisolone	The imidazole, itraconazole, may increase the effect and toxicity of the corticosteroid, prednisolone.
Conivaptan	Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.
Risperidone	Increases the level of risperidone
Almotriptan	This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Sirolimus	Itraconazole may increase the effect and toxicity of sirolimus.
Clonazepam	Itraconazole may increase the effect of the benzodiazepine, clonazepam.
Alfentanil	Itraconazole may increase the effect and toxicity of alfentanil.
Dicumarol	Itraconazole may increase the anticoagulant effect of dicumarol.
Lansoprazole	The proton pump inhibitor, lansoprazole, may decrease the absorption of itraconazole.
Haloperidol	Itraconazole may increase the effect and toxicity of haloperidol.
Zopiclone	Itraconazole, 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.
Telithromycin	Itraconazole may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.
Astemizole	Increased risk of cardiotoxicity and arrhythmias
Mestranol	This anti-infectious agent could decrease the effect of the oral contraceptive
Alprazolam	Itraconazole may increase the effect of the benzodiazepine, alprazolam.
Tacrolimus	The 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.
Eplerenone	Itraconazole may increase the effect and toxicity of eplerenone.
Quinidine barbiturate	Itraconazole may increase the effect and toxicity of quinidine barbiturate.
Trimipramine	The 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.
Estazolam	Itraconazole may increase the effect of the benzodiazepine, estazolam.
Quazepam	Itraconazole may increase the effect of the benzodiazepine, quazepam.
Ranitidine	The H2-receptor antagonist, ranitidine, may decrease the absorption of itraconazole.
Diazepam	Itraconazole may increase the effect of the benzodiazepine, diazepam.
Cilostazol	Itraconazole may increase the effect of cilostazol.
Vinorelbine	Itraconazole, 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.
Famotidine	The H2-receptor antagonist, famotidine, may decrease the absorption of itraconazole.
Temsirolimus	Itraconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Bosentan	Itraconazole may increase the effect and toxicity of bosentan.
Nizatidine	The H2-receptor antagonist, nizatidine, may decrease the absorption of itraconazole.
Magnesium oxide	The antacid, magnesium oxide, may decrease the effect of itraconazole by decreasing its absorption.
Verapamil	Itraconazole, 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.
Felodipine	Itraconazole may increase the therapeutic and adverse effects of felodipine.
Warfarin	Itraconazole may increase the anticoagulant effect of warfarin by decreasing its metabolism.
Josamycin	The macrolide, josamycin, may increase the effect and toxicity of itraconazole.
Sucralfate	Sucralfate may decrease the absorption of itraconazole.
Fosphenytoin	Phenytoin decreases the effect of itraconazole
Cimetidine	The H2-receptor antagonist, cimetidine, may decrease the absorption of itraconazole.
Ethotoin	Phenytoin decreases the effect of itraconazole
Budesonide	Itraconazole may increase levels/effect of budesonide.
Acenocoumarol	Itraconazole may increase the anticoagulant effect of acenocoumarol.
Phenytoin	Phenytoin decreases the effect of itraconazole
Dofetilide	This strong CYP3A4 inhibitor increases the effect and toxicity of dofetilide
Tramadol	Itraconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Midazolam	Itraconazole may increase the effect of the benzodiazepine, midazolam.
Fentanyl	Itraconazole may increase levels/toxicity of fentanyl.
Clarithromycin	The macrolide, clarithromycin, may increase the effect and toxicity of itraconazole.
Eletriptan	This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Carbamazepine	Itraconazole may increase the effect of carbamazepine.
Venlafaxine	Itraconaole, 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.
Halazepam	Itraconazole may increase the effect of the benzodiazepine, halazepam.
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Dantrolene	Itraconazole 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.
Calcium carbonate	The antacid, calcium carbonate, may decrease the effect of itraconazole by decreasing its absorption.
Cerivastatin	Increased risk of myopathy/rhabdomyolysis
Alfuzosin	The antifungal increases the effect of alfuzosin
Aprepitant	This CYP3A4 inhibitor, itraconazole, may increase the effect and toxicity of aprepitant.
Vardenafil	Itraconazole, a potent CYP3A4 inhibitor, may decrease the metabolism and clearance of Vardenafil. Concomitant therapy is contraindicated.
Dihydroergotamine	Possible ergotism and severe ischemia with this combination
Solifenacin	This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Rifampin	Rifampin may decrease the effect of itraconazole.
Simvastatin	Increased risk of myopathy/rhabdomyolysis
Lovastatin	Increased risk of myopathy/rhabdomyolysis
Calcium	Calcium-containing antacids may decrease the effect of itraconazole.
Trazodone	The 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.
Cyclosporine	Itraconazole may increase the effect of cyclosporine.
Aluminium	Aluminum-containing antacids may decrease the effect of itraconazole.
Vinblastine	Itraconazole, 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.
Pimozide	Increased risk of cardiotoxicity and arrhythmias
Rifabutin	Rifabutin decreases the effect of itraconazole
Methylprednisolone	The imidazole, itraconazole, may increase the effect and toxicity of the corticosteroid, methylprednisolone.
Teniposide	The 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.
Digoxin	Itraconazole increases the effect of digoxin
Esomeprazole	The proton pump inhibitor, esomeprazole, may decrease the absorption of itraconazole.
Tamsulosin	Itraconazole, 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.
Chlordiazepoxide	Itraconazole may increase the effect of the benzodiazepine, chlordiazepoxide.
Tadalafil	Itraconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tolterodine	Itraconazole may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Anisindione	Itraconazole may increase the anticoagulant effect of anisindione.
Sunitinib	Possible increase in sunitinib levels
Ciclesonide	Increased effects/toxicity of ciclesonide
Vincristine	Itraconazole, 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.
Pantoprazole	The proton pump inhibitor, pantoprazole, may decrease the absorption of itraconazole.
Erythromycin	The macrolide, erythromycin, may increase the effect and toxicity of itraconazole.
Gefitinib	Itraconazole, 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.
Zolpidem	Itraconazole, 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.
Levomethadyl Acetate	Itraconazole increases the effect/toxicity of levomethadyl
Erlotinib	Itraconazole 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.
Flurazepam	Itraconazole may increase the effect of the benzodiazepine, flurazepam.
Imatinib	Itraconazole may increase the levels of imatinib.
Triazolam	Itraconazole may increase the effect of the benzodiazepine, triazolam.
Sildenafil	Itraconazole may increase the effect and toxicity of sildenafil.
Tipranavir	Tipranavir may increase the serum concentration of Itraconazole.
Ranolazine	Increased levels of ranolazine - risk of toxicity
Darifenacin	This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Bromazepam	Itraconazole 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.
Mephenytoin	Phenytoin decreases the effect of itraconazole
Quinidine	Itraconazole may increase the effect and toxicity of quinidine.
Rivaroxaban	Use of rivaroxaban with agents that are strong inhibitors of both CYP3A4 and P-glycoproteins are contraindicated.
Zonisamide	Itraconazole, 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.
Prednisone	The imidazole, itraconazole, may increase the effect and toxicity of the corticosteroid, prednisone.
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Ritonavir	Itraconazole may increase the effect and toxicity of ritonavir.
Celiprolol	Itaconazole increases levels/effect of celiprolol
Atorvastatin	Increased risk of myopathy/rhabdomyolysis
Everolimus	Itraconazole may increase everolimus levels/toxicity.
Phenobarbital	The barbiturate, phenobarbital, decreases the effect of itraconazole.
Topotecan	The 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.
Tamoxifen	Itraconazole may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
Ergotamine	Possible ergotism and severe ischemia with this combination
Cinacalcet	Itraconazole may increase the effect and toxicity of cinacalcet.
Rabeprazole	The proton pump inhibitor, rabeprazole, may decrease the absorption of itraconazole.
Aripiprazole	Itraconazole may increase the effect of aripiprazole.

Targets

Enzymes

Transporters

Multidrug resistance protein 1