Itraconazole

705.63300

705.63

617-596-9

759239

DTXSID3023180

Solid|Crystals from toluene

QJ02AC02|J02AC02|J - Antiinfectives for systemic use

2934999090

104.70000

5.66 (LogP)

off-White crystalline solid

1.27 g/cm³

166.2 °C

850ºC at 760 mmHg

467.9ºC

1.678

chloroform: 50 mg/mL, clear, colorless

2-8ºC

2.6X10-20 mm Hg at 25 °C (est)

LD50 (14 day) in mice, rats, dogs (mg/kg): >320, >320, >200 orally (Van Cauteren)

3.70|pKa = 3.7

NONH for all modes of transport

3

R36/37/38

S22-S26-S36

XZ5481000

Xi

Stable. Incompatible with strong oxidizing agents.

P261-P305 + P351 + P338

H302-H315-H319-H335

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

/Incompatible with/ oxidizing agents.|The manufacturer states that itraconazole injection should not be diluted with 5% dextrose injection or with lactated Ringer's injection, alone or in combination with any other diluent, since information is not available regarding the physical and/or chemical compatibility of itraconazole with these diluents.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including itraconazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 2 companies from 1 notifications to the ECHA C&L Inventory.|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 146 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Engineering controls such as exhaust ventilation are recommended.|Use a NIOSH-approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.

Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials.|As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Wear approved respiratory protection, chemically compatible gloves and protective clothing. Wipe up spillage or collect spillage using a high-efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately -labelled container for disposal. Wash spill site.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|This material is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.|As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.|/Wear/ chemically compatible gloves, safety glasses or goggles /and/ protect exposed skin.

May cause irritation /upon inhalation/. Remove to fresh air. May cause /eye/ irritation. Flush with copious quantities of water. May cause irritation /to skin/. Flush with copious quantities of water.

As a secondary release pathway to the environment, bathing, washing, and laundering have been suggested as possible release routes following consumer use of pharmaceuticals. Itraconzole is mostly excreted through sebaceous glands and moderately excreted by the sweat glands, based upon data compiled using a sweat patch or wipe(1).

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.

Transient, mild-to-moderate elevations in serum aminotransferase levels occur in 1% to 5% of patients on itraconazole. These elevations are largely asymptomatic and self-limited, resolving even with continuation of therapy. Clinically apparent hepatotoxicity is rare but has been well described and can be severe and even fatal. The liver injury from itraconazole typically presents 1 to 6 months after starting therapy with symptoms of fatigue and jaundice. The pattern of serum enzyme elevations is typically cholestatic (Case 1), but cases of severe hepatitis with acute liver failure typically have a hepatocellular enzyme pattern (Case 2). Immunoallergic features (rash, fever, eosinophilia) are uncommon as is autoantibody formation. Recovery upon stopping therapy can be delayed for several weeks and generally takes 4 to 10 weeks, although in some cases recovery may be prolonged.

The class IA antiarrhythmic quinidine and class III antiarrhythmic dofetilide are known to prolong the QT interval. Co-administration of quinidine or dofetilide with itraconazole may increase plasma concentrations of quinidine or dofetilide which could result in serious cardiovascular events. Therefore, concomitant administration of itraconazole and quinidine or dofetilide is contraindicated. The class IA antiarrhythmic disopyramide has the potential to increase the QT interval at high plasma concentrations. Caution is advised when itraconazole and disopyramide are administered concomitantly. Concomitant administration of digoxin and itraconazole has led to increased plasma concentrations of digoxin.|Reduced plasma concentrations of itraconazole were reported when itraconazole was administered concomitantly with phenytoin. Carbamazepine, phenobarbital and phenytoin are all inducers of CYP3A4. Although interactions with carbamazepine and phenobarbital have not been studied, concomitant administration of itraconazole and these drugs would be expected to result in decreased plasma concentrations of itraconazole.|Drug interaction studies have demonstrated that plasma concentrations of azole antifungal agents and their metabolites, including itraconazole and hydroxyitraconazole, were significantly decreased when these agents were given concomitantly with rifabutin or rifampin. In vivo data suggest that rifabutin is metabolized in part by CYP3A4. Itraconazole may inhibit the metabolism of rifabutin.|Itraconazole may inhibit the metabolism of busulfan, docetaxel and vinca alkaloids.|For more Interactions (Complete) data for Itraconazole (29 total), please visit the HSDB record page.

LD50 Rat oral >320 mg/kg|LD50 Mouse oral >320 mg/kg|LD50 Dog oral >200 mg/kg|LD50 Guinea pig oral >160 mg/kg

Itraconazole Capsules should not be administered for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF. If signs or symptoms of congestive heart failure occur during administration of itraconazole capsules, discontinue administration. When itraconazole was administered intravenously to dogs and healthy human volunteers, negative inotropic effects were seen.

99.8%

Itraconazole's production and use as a medication(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 6,600(SRC), determined from a log Kow of 5.66(2) and a regression-derived equation(3), indicates that itraconazole is expected to be immobile in soil(SRC). The pKa of itraconazole is 3.7(4), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Itraconazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.6X10-20 mm Hg at 25 °C(SRC), determined from a fragment constant method(6). A biodegradation model indicates persistence on the order of months and longer(7), suggesting that biodegradation is not expected to be an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 6,600(SRC), determined from a log Kow of 5.66(2) and a regression-derived equation(3), indicates that itraconazole is expected to adsorb to suspended solids and sediment(SRC). A pKa of 3.7(4) indicates itraconazole will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(5), an estimated BCF of 2,500(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). A biodegradation model indicates persistence on the order of months and longer(6), suggesting that biodegradation is not expected to be an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), itraconazole, which has an estimated vapor pressure of 2.6X10-20 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase itraconazole may be removed from the air by wet or dry deposition(SRC). Itraconazole does not contain chromophores that absorb at wavelengths >290 nm(3), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Itraconazole is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Itraconazole does not contain chromophores that absorb at wavelengths >290 nm(1), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 2,500 was calculated in fish for itraconazole(SRC), using a log Kow of 5.66(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC).

The Koc of itraconazole is estimated as 6,600(SRC), using a log Kow of 5.66(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that itraconazole is expected to be immobile in soil. The pKa of itraconazole is 3.7(4), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

A pKa of 3.7(1) indicates itraconazole will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water and moist soil surfaces is not expected to be an important fate process(SRC). Itraconazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.6X10-20 mm Hg(SRC), determined from a fragment constant method(2).

Itraconazole is distributed into human milk and the expected benefits of itraconazole for the nursing woman should be weighed against the potential risk to the infant from exposure to the drug.

Occupational exposure to itraconazole may occur through inhalation and dermal contact with this compound at workplaces where itraconazole is produced or used. Exposure to itraconazole among the general population may be limited to those administered the drug, an antifungal. (SRC)

For the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: pulmonary and extrapulmonary blastomycosis, histoplasmosis, aspergillosis, and onychomycosis.|FDA Label|For the treatment of aspergillosis and candidiasis in companion birds,

Itraconazole is a orally administered, triazole antifungal agent used in the treatment of systemic and superficial fungal infections. Itraconazole therapy is associated with transient, mild-to-moderate serum elevations and can lead to clinically apparent acute drug induced liver injury.

Antifungal Agents

Antifungal Agents; Antiprotozoal Agents|Itraconazole capsules are indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary; Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis and Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapy. /Included in US product label/|Itraconazole capsules are also indicated for the treatment of the following fungal infections in non-immunocompromised patients: Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium) and Onychomycosis of the fingernail due to dermatophytes (tinea unguium). /Included in US product label/

/BOXED WARNING/ Congestive Heart Failure, Cardiac Effects: Itraconazole capsules should not be administered for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF. If signs or symptoms of congestive heart failure occur during administration of itraconazole capsules, discontinue administration. When itraconazole was administered intravenously to dogs and healthy human volunteers, negative inotropic effects were seen.|/BOXED WARNING/ Drug Interactions: Coadministration of the following drugs are contraindicated with itraconazole capsules: methadone, disopyramide, dofetilide, dronedarone, quinidine, ergot alkaloids (such as dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergometrine (methylergonovine)), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ranolazine, eplerenone, cisapride, lovastatin, simvastatin and, in subjects with renal or hepatic impairment, colchicine. Coadministration with itraconazole can cause elevated plasma concentrations of these drugs and may increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs. For example, increased plasma concentrations of some of these drugs can lead to QT prolongation and ventricular tachyarrhythmias including occurrences of torsades de pointes, a potentially fatal arrhythmia.|Itraconazole is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation. Although information concerning cross-sensitivity between itraconazole and other triazole or imidazole antifungal agents is not available, the manufacturer states that itraconazole should be used with caution in individuals hypersensitive to other azoles.|Adverse GI effects have been reported in about 1-11% of patients receiving IV or oral itraconazole for the treatment of systemic fungal infections or oropharyngeal or esophageal candidiasis or for empiric anti-fungal therapy. These adverse GI effects usually are transient and respond to symptomatic treatment without alteration of itraconazole therapy; however, reduction of dosage or discontinuance of the drug occasionally may be required.|For more Drug Warnings (Complete) data for Itraconazole (27 total), please visit the HSDB record page.

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.

Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. (See all compounds classified as Antifungal Agents.)|Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP3A. (See all compounds classified as Cytochrome P-450 CYP3A Inhibitors.)|Compounds that specifically inhibit STEROL 14-DEMETHYLASE. A variety of azole-derived ANTIFUNGAL AGENTS act through this mechanism. (See all compounds classified as 14-alpha Demethylase Inhibitors.)

The absolute oral bioavailability of itraconazole is 55%, and is maximal when taken with a full meal.|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.|796 ± 185 L|381 +/- 95 mL/minute [IV administration]|The pharmacokinetics of itraconazole after intravenous administration and its absolute oral bioavailability from an oral solution were studied in a randomized crossover study in 6 healthy male volunteers. The observed absolute oral bioavailability of itraconazole was 55%.|The oral bioavailability of itraconazole is maximal when itraconazole capsules are taken with a full meal. The pharmacokinetics of itraconazole were studied in 6 healthy male volunteers who received, in a crossover design, single 100 mg doses of itraconazole as a polyethylene glycol capsule, with or without a full meal. The same 6 volunteers also received 50 mg or 200 mg with a full meal in a crossover design. In this study, only itraconazole plasma concentrations were measured. The respective pharmacokinetic parameters for itraconazole are presented in the table /provided/.|Steady-state concentrations were reached within 15 days following oral doses of 50 mg to 400 mg daily. Values given in the table below are data at steady-state from a pharmacokinetics study in which 27 healthy male volunteers took 200 mg itraconazole capsules b.i.d. (with a full meal) for 15 days [Table#7592]|Thirty healthy men received single 200 mg doses of itraconazole capsules under fasted conditions either 1) with water; 2) with water, after ranitidine 150 mg b.i.d. for 3 days; or 3) with cola, after ranitidine 150 mg b.i.d. for 3 days. When itraconazole capsules were administered after ranitidine pretreatment, itraconazole was absorbed to a lesser extent than when itraconazole capsules were administered alone, with decreases in AUC0-24 and Cmax of 39% +/- 37% and 42% +/- 39%, respectively. When itraconazole capsules were administered with cola after ranitidine pretreatment, itraconazole absorption was comparable to that observed when itraconazole capsules were administered alone.|For more Absorption, Distribution and Excretion (Complete) data for Itraconazole (11 total), please visit the HSDB record page.

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.|Itraconazole is metabolized predominantly by the cytochrome P450 3A4 isoenzyme system (CYP3A4), resulting in the formation of several metabolites, including hydroxyitraconazole, the major metabolite. Results of a pharmacokinetics study suggest that itraconazole may undergo saturable metabolism with multiple dosing.|Itraconazole (ITZ) is metabolized in vitro to three inhibitory metabolites: hydroxy-itraconazole (OH-ITZ), keto-itraconazole (keto-ITZ), and N-desalkyl-itraconazole (ND-ITZ). The goal of this study was to determine the contribution of these metabolites to drug-drug interactions caused by ITZ. Six healthy volunteers received 100 mg ITZ orally for 7 days, and pharmacokinetic analysis was conducted at days 1 and 7 of the study. The extent of CYP3A4 inhibition by ITZ and its metabolites was predicted using this data. ITZ, OH-ITZ, keto-ITZ, and ND-ITZ were detected in plasma samples of all volunteers. A 3.9-fold decrease in the hepatic intrinsic clearance of a CYP3A4 substrate was predicted using the average unbound steady-state concentrations (C(ss,ave,u)) and liver microsomal inhibition constants for ITZ, OH-ITZ, keto-ITZ, and ND-ITZ. Accounting for circulating metabolites of ITZ significantly improved the in vitro to in vivo extrapolation of CYP3A4 inhibition compared to a consideration of ITZ exposure alone.

21 hours

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.|In vitro studies have demonstrated that itraconazole inhibits the cytochrome P450-dependent synthesis of ergosterol, which is a vital component of fungal cell membranes.

Impurities: 4-[4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]-2-[(1RS)-1-methylpropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one; 4-[4-[4-[4-[[cis-2-(2,4-dichlorophenyl)-2-(4H-1,2,4-triazol-4-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(1RS)-1-methylpropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one; 4-[4-[4-[4-[[cis-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-propyl-2,4-dihydro-3H-1,2,4-triazol-3-one; 4-[4-[4-[4-[[cis-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-(1-methylethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one; 4-[4-[4-[4-[[trans-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(1RS)-1-methylpropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one; 2-butyl-4-[4-[4-[4-[[cis-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one; 4-[4-[4-[4-[[cis-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[[cis-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/CASE REPORTS/ Itraconazole is a widely prescribed triazole antifungal drug, often given for long periods. The authors report five cases of tremor related to itraconazole therapy, which occurred within 1-12 months of initiating treatment and resolved gradually following itraconazole withdrawal.|/CASE REPORTS/ ... Three patients with apparent itraconazole-induced liver injury were studied. Clinical, laboratory, serologic, and histologic data of all three cases were analyzed. All three patients developed a biochemical-histologic pattern of cholestatic liver injury with damage to the interlobular bile ducts. Beginning ductopenia was present in two, suggesting that itraconazole might be responsible for the occurrence of prolonged drug-induced cholangiopathy. Jaundice was the presenting symptom in all three. It was not accompanied by clinical hallmarks of hypersensitivity, which is suggestive for metabolic rather than for immunoallergic idiosyncrasy. Itraconazole-induced liver injury presents with a cholestatic pattern of injury with damage to the interlobular bile ducts, possibly leading to ductopenia. ...|/CASE REPORTS/ Itraconazole is widely used to treat onychomycosis because of its significant therapeutic effects. An otherwise healthy 30-year-old man treated with itraconazole developed frequent premature ventricular contractions (PVC). He presented with a dry cough and palpitation. The results of 12-lead electrocardiography (ECG) were essentially normal, but Holter ECG revealed 17,484 (18%) uniform PVC, including 4 short runs among 96,930 beats/day. Another Holter ECG after withdrawing itraconazole revealed 1,032 premature atrial contractions but no PVC. The corrected QT interval was 0.39 s without itraconazole, 0.41 s with itraconazole, and 0.43 s when multiple PVC were documented. Itraconazole inhibits the fungal cytochrome P450 that is involved in fungal cell membrane formation, interrupts human cytochrome P450A4 in the liver and causes adverse interactions with various drugs such as antiarrythmics, but its cardiac side-effects are obscure. Both patients and physicians should be aware that itraconazole can cause PVC as a side-effect.|/CASE REPORTS/ An 80-year-old man was admitted to the hospital with a diagnosis of pulmonary aspergilloma. A new azole antifungal agent, D 0870, was administered to the patient for 7 days orally, and itraconazole (400 mg/day) was started. After 1 month of chemotherapy, facial and pretibial edema were observed and the patient's serum potassium concentration decreased to 2.5 mEq/L. A chest radiograph disclosed cardiomegaly with cardiac effusion and right pleural effusion on admission. The serum potassium concentration rose after the cessation of itraconazole therapy. The serum ITCZ concentration remained high for 2 weeks after admission. Although reports of hypopotassemia induced by ITCZ are rare, /investigators/ concluded that blood concentrations should be monitored more carefully when treating pulmonary aspergilloma patients with high-dose regimens of ITCZ.|For more Human Toxicity Excerpts (Complete) data for Itraconazole (21 total), please visit the HSDB record page.

Itraconazole

Itraconazole preparations: (AHFS, 2010)

Analyte: itraconazole; matrix: blood (plasma, serum), tissue (liver (bird)); procedure: high performance liquid chromatography with fluorescence detection at 260 nm (excitation) and 365 nm (emission); limit of detection: 5 ng/mL|Analyte: itraconazole; matrix: blood (plasma), tissue; procedure: high performance liquid chromatography with ultraviolet detection at 261 nm; limit of detection: 10 ng/g (tissue), 5 ng/mL (blood)|Analyte: itraconazole; matrix: blood (serum); procedure: high performance liquid chromatography with ultraviolet detection at 263 nm; limit of detection: 10 ng/mL|Analyte: itraconazole; matrix: blood (plasma); procedure: high performance liquid chromatography with ultraviolet detection at 263 nm; limit of detection: 20 ug/mL|For more Clinical Laboratory Methods (Complete) data for Itraconazole (15 total), please visit the HSDB record page.

Veterinary drugs -> Fungitraxx -> EMA Drug Category|Antimycotics for systemic use, Triazole derivatives, itraconazole -> Veterinary pharmacotherapeutic group|Human drugs -> Rare disease (orphan)|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients|Fungicides