QuickView for ketoconazole (compound)

Summary
General Info

PubChem

PubChem Compound 3823

Name:	Ketoconazole
PubChem Compound ID:	3823
Description:	Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.
Molecular formula:	C₂₆H₂₈Cl₂N₄O₄
Molecular weight:	531.43 g/mol
Synonyms:	(+-)-cis-1-acetyl-4-(p-((2-(2,4-dichlorophenyl)-2-(imidazol-1- ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine; ketoconazol; ketoisdin; 79156-75-5; Ketoconazole; CPD-4503; fungarest; orifungal M; NSC317629; fungoral. show more » (+-)-cis-1-acetyl-4-(p-((2-(2,4-dichlorophenyl)-2-(imidazol-1- ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine; ketoconazol; ketoisdin; 79156-75-5; Ketoconazole; CPD-4503; fungarest; orifungal M; NSC317629; fungoral; Nizoral; NCI60_002728; Panfungol; piperazine, 1-acetyl-4-(4-((2-(2,4-dichlorophenyl)-2-(1H- imidazol-1-ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)-, cis-; KW 1414; Ketoderm show less «

DrugBank

Identification

Name:	Ketoconazole
Name (isomeric):	DB01026
Drug Type:	small molecule
Description:	Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.
Synonyms:	2%; Ketoconazol [INN-Spanish]; Ketoconazolum [INN-Latin]; Ketocanazole; Ketoconazol; Ketoconazole [Usan:Ban:Inn:Jan]
Brand:	Fungoral, Ketoderm, Nizoral, Nizoral a-D Shampoo, Nizoral Cream, Orifungal M, Sebazole, Orifungal, Fungarest, Extina, Ketoisdin, Nizoral a-D, Nizoral Shampoo, Panfungol, Ketozole
Category:	Antifungal Agents, Antifungals
CAS number:	65277-42-1

Pharmacology

Indication:	For the treatment of the following systemic fungal infections: candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis.
Pharmacology:	Ketoconazole, like clotrimazole, fluconazole, itraconazole, and miconazole, is an imidazole antifungal agent.
Mechanism of Action:	Ketoconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibit... show more » Ketoconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibition of yeast transformation to mycelial forms, inhibition of purine uptake, and impairment of triglyceride and/or phospholipid biosynthesis. Ketoconazole can also inhibit the synthesis of thromboxane and sterols such as aldosterone, cortisol, and testosterone. show less «
Absorption:	Moderate
Protein binding:	99% (in vitro, plasma protein binding)
Biotransformation:	Hepatic
Half Life:	2 hours
Toxicity:	Hepatotoxicity, LD₅₀=86 mg/kg (orally in rat)
Affected organisms:	Fungi

Interactions

Food interaction:

Avoid alcohol.

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 with food.

Drug interaction:

Estazolam	Ketoconazole may increase the effect of the benzodiazepine, estazolam.
Halazepam	Ketoconazole may increase the effect of the benzodiazepine, halazepam.
Budesonide	Ketoconazole may increase levels/effect of budesonide.
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.
Tolbutamide	Ketoconazole, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Ketoconazole is initiated, discontinued or dose changed.

Estazolam	Ketoconazole may increase the effect of the benzodiazepine, estazolam.
Halazepam	Ketoconazole may increase the effect of the benzodiazepine, halazepam.
Budesonide	Ketoconazole may increase levels/effect of budesonide.
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.
Tolbutamide	Ketoconazole, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Ketoconazole is initiated, discontinued or dose changed.
Diazepam	Ketoconazole may increase the effect of the benzodiazepine, diazepam.
Almotriptan	This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Vardenafil	Ketoconazole, a potent CYP3A4 inhibitor, may decrease the metabolism and clearance of Vardenafil. Concomitant therapy is contraindicated.
Pioglitazone	Ketoconazole increases the effect of pioglitazone
Sibutramine	Ketoconazole increases the levels and toxicity of sibutramine
Cyclosporine	Ketoconazole may increase the effect of cyclosporine.
Aprepitant	This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
Quetiapine	Ketoconazole may increase the therapeutic and adverse effects of quetiapine.
Torasemide	Ketoconazole, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Ketoconazole is initiated, discontinued or dose changed.
Haloperidol	Ketoconazole may increase the effect and toxicity of haloperidol.
Glimepiride	Ketoconazole increases the effect of rosiglitazone
Astemizole	Increased risk of cardiotoxicity and arrhythmias
Isoniazid	Isoniazid decreases the effect of ketoconazole
Mestranol	This anti-infectious agent could decrease the effect of the oral contraceptive
Verapamil	Ketoconazole, 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 Ketoconazole is initiated, discontinued or dose changed.
Rabeprazole	The proton pump inhibitor, rabeprazole, may decrease the absorption of ketoconazole.
Calcium	Calcium-containing antacids may decrease the absorption of ketoconazole.
Tamoxifen	Ketoconazole may increase the serum concentration of Tamoxifen by decreasing its metabolism and clearance. Ketoconazole may also decrease the therapeutic effect of Tamoxifen by decreasing active metabolite production. Monitor for changes in the therapeutic/adverse effects of Tamoxifen if Ketoconazole is initiated, discontinued or dose changed.
Ritonavir	Ketoconazole may increase the effect and toxicity of ritonavir.
Tolterodine	Ketoconazole may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Eplerenone	Ketoconazole, a CYP3A4 inhibitor, may increase the effect and toxicity of eplerenone.
Galantamine	Ketoconazole increases the effect and toxicity of galantamine
Aripiprazole	Ketoconazole may increase the effect of aripiprazole.
Sildenafil	Ketoconazole may increase the effect and toxicity of sildenafil.
Lansoprazole	The proton pump inhibitor, lansoprazole, may decrease the absorption of ketoconazole.
Ramelteon	Ketoconazole may increase the serum levels and toxicity of ramelteon.
Anisindione	Ketoconazole may increase the anticoagulant effect of anisindione.
Imatinib	Ketoconazole may increase the levels of imatinib.
Docetaxel	Ketoconazole may increase the serum levels and toxicity of docetaxel.
Nevirapine	Nevirapine, a strong CYP3A4 inducer, may decrease the serum concentration of ketoconazole by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of ketoconazole if nevirapine is initiated, discontinued or dose changed.
Vinblastine	Ketoconazole, 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 Ketoconazole is initiated, discontinued or dose changed.
Quazepam	Ketoconazole may increase the effect of the benzodiazepine, quazepam.
Tacrine	The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Ketoconazole. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Ketoconazole is initiated, discontinued or if the dose is changed.
Valdecoxib	Ketoconazole may increase the effect and toxicity of valdecoxib.
Telithromycin	Ketoconazole may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.
Tizanidine	Ketoconazole may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Venlafaxine	Ketoconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Ketoconazole is initiated, discontinued, or dose changed.
Dofetilide	This strong CYP3A4 inhibitor increases the effect and toxicity of dofetilide
Tipranavir	Tipranavir may increase the serum concentration of Ketoconazole.
Clonazepam	Ketoconazole may increase the effect of the benzodiazepine, clonazepam.
Midazolam	Ketoconazole may increase the effect of the benzodiazepine, midazolam.
Temsirolimus	Ketoconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Trimethoprim	The strong CYP2C9 inhibitor, Ketoconazole, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Ketoconazole is initiated, discontinued or dose changed.
Sucralfate	Sucralfate may decrease the absorption of ketoconazole.
Eletriptan	This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Flurazepam	Ketoconazole may increase the effect of the benzodiazepine, flurazepam.
Sirolimus	Ketoconazole may increase the effect and toxicity of sirolimus.
Bromazepam	Ketoconazole may increase the serum concentration of bromazepam by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of bromazepam if ketoconazole is initiated, discontinued or dose changed.
Dantrolene	Ketoconazole 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 ketoconazole is initiated, discontinued or dose changed.
Famotidine	The H2-receptor antagonist, famotidine, may decrease the absorption of ketoconazole.
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Saquinavir	Ketoconazole may increase the effect and toxicity of saquinavir.
Tamsulosin	Ketoconazole, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Ketoconzole is initiated, discontinued, or dose changed.
Ziprasidone	Ketoconazole increases the effect and toxicity of ziprasidone
Erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib
Pantoprazole	The proton pump inhibitor, pantoprazole, may decrease the absorption of ketoconazole.
Quinidine barbiturate	Ketoconazole may increase the effect and toxicity of quinidine barbiturate.
Cerivastatin	Increased risk of myopathy/rhabdomyolysis
Alfuzosin	The antifungal increases the effect of alfuzosin
Cinacalcet	Ketoconazole may increase the effect and toxicity of cinacalcet.
Prednisone	The imidazole, ketoconazole, may increase the effect and toxicity of the corticosteroid, prednisone.
Trimipramine	The strong CYP3A4 inhibitor, Ketoconazole, 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 Ketoconazole is initiated, discontinued or dose changed.
Ergotamine	Possible ergotism and severe ischemia with this combination.
Teniposide	The strong CYP3A4 inhibitor, Ketoconazole, 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 Ketoconazole is initiated, discontinued or dose changed.
Clorazepate	Ketoconazole may increase the effect of the benzodiazepine, clorazepate.
Dihydroergotamine	Possible ergotism and severe ischemia with this combination
Solifenacin	This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Acenocoumarol	Ketoconazole may increase the anticoagulant effect of acenocoumarol.
Simvastatin	Increased risk of myopathy/rhabdomyolysis
Lovastatin	Increased risk of myopathy/rhabdomyolysis
Vilazodone	CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. imit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors.
Tadalafil	Ketoconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Fentanyl	Ketoconazole may increase levels/toxicity of fentanyl.
Pimozide	Increased risk of cardiotoxicity and arrhythmias
Ranitidine	The H2-receptor antagonist, ranitidine, may decrease the absorption of ketoconazole.
Quinidine	Ketoconazole may increase the effect and toxicity of quinidine.
Warfarin	Ketoconazole, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if ketoconazole is initiated, discontinued or dose changed.
Prednisolone	The imidazole, ketoconazole, may increase the effect and toxicity of the corticosteroid, prednisolone.
Everolimus	Ketoconazole may increase everolimus levels/toxicity.
Amitriptyline	Ketoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of amitriptyline by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if ketoconazole is initiated, discontinued or dose changed.
Tacrolimus	The antifungal, Ketoconazole, may increase serum concentrations of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Ketoconzole therapy is initiated, discontinued or altered.
Sunitinib	Possible increase in sunitinib levels
Ciclesonide	Increased effects/toxicity of ciclesonide
Carbamazepine	Ketoconazole may increase the effect of carbamazepine.
Rosiglitazone	Ketoconazole increases the effect of rosiglitazone
Bosentan	Ketoconazole may increase the effect and toxicity of bosentan.
Triazolam	Ketoconazole may increase the effect of the benzodiazepine, triazolam.
Alfentanil	Ketoconazole may increase the effect and toxicity of alfentanil.
Gefitinib	This CYP3A4 inhibitor increases levels/toxicity of gefitinib
Tiagabine	The strong CYP3A4 inhibitor, Ketoconazole, 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 Ketoconazole is initiated, discontinued or dose changed.
Dicumarol	Ketoconazole may increase the anticoagulant effect of dicumarol.
Ranolazine	Increased levels of ranolazine - risk of toxicity
Darifenacin	This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Zonisamide	Ketonconazole, 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 ketoconazole is initiated, discontinued or dose changed.
Aluminium	Aluminum-containing antacids may decrease the effect of ketoconazole.
Nortriptyline	Ketoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of nortriptyline by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if ketoconazole is initiated, discontinued or dose changed.
Vincristine	Ketoconazole, 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 Ketoconazole is initiated, discontinued or dose changed.
Trazodone	The CYP3A4 inhibitor, Ketoconazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Ketoconazole is initiated, discontinued or dose changed.
Magnesium oxide	The antacid, magnesium oxide, may decrease the effect of ketoconazole by decreasing its absorption.
Methylprednisolone	The imidazole, ketoconazole, may increase the effect and toxicity of the corticosteroid, methylprednisolone.
Tramadol	Ketoconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Ketoconazole may decrease the effect of Tramadol by decreasing active metabolite production.
Alprazolam	Ketoconazole may increase the effect of the benzodiazepine, alprazolam.
Ethinyl Estradiol	This anti-infectious agent could decrease the effect of the oral contraceptive
Rivaroxaban	Use of rivaroxaban with agents that are strong inhibitors of both CYP3A4 and P-glycoproteins are contraindicated.
Zolpidem	Ketoconazole, 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 ketoconazole is initiated, discontinued or dose changed.
Thiothixene	The strong CYP1A2 inhibitor, Ketoconazole, may decrease the metabolism and clearance of Thiothixene, a CYP1A2 substrate. Consider alternate therapy or monitor for changes in Thiothixene therapeutic and adverse effects if Ketoconazole is initiated, discontinued or dose changed.
Cimetidine	The H2-receptor antagonist, cimetidine, may decrease the absorption of ketoconazole.
Omeprazole	The proton pump inhibitor, omeprazole, may decrease the absorption of ketoconazole.
Vinorelbine	Ketoconazole, 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 Ketoconazole is initiated, discontinued or dose changed.
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Indinavir	Indinavir may increase the serum concentration of ketoconazole. Ketoconazole may increase the serum concentration of indinavir. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if either agent is initiated, discontinued or dose changed.
Atorvastatin	Increased risk of myopathy/rhabdomyolysis
Chlordiazepoxide	Ketoconazole may increase the effect of the benzodiazepine, chlordiazepoxide.
Voriconazole	Ketoconazole, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if ketoconazole is initiated, discontinued or dose changed.
Irinotecan	Ketoconazole increases the effect and toxicity of irinotecan
Esomeprazole	The proton pump inhibitor, esomeprazole, may decrease the absorption of ketoconazole.
Rifampin	Rifampin may decrease the effect of ketoconazole.
Zafirlukast	Ketoconazole, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if ketoconazole is initiated, discontinued or dose changed.
Zopiclone	Ketonconazole, 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 ketoconazole is initiated, discontinued or dose changed.
Topotecan	The p-glycoprotein inhibitor, Ketoconazole, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Cilostazol	Ketoconazole may increase the effect of cilostazol.
Imipramine	Ketoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of imipramine by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if ketoconazole is initiated, discontinued or dose changed.
Nizatidine	The H2-receptor antagonist, nizatidine, may decrease the absorption of ketoconazole.