| GHS 분류 | WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 88 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
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| 기타 안전 정보 | IMAP assessments - 3H-1,2,4-Triazol-3-one, 4-[4-[4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-2,4-dihydro-2-(1-methylpropyl)-: Environment tier I assessment |
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| FDA 요건 | 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. |
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| Hazard Classes and Categories | Acute Tox. 4 (100%) |
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| Skin, Eye, and Respiratory Irritations | 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. |
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| Hazardous Reactivities and Incompatibilities | /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. |
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| 소화 절차 | 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. |
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| 보관 조건 | Itraconazole capsules should be stored at a controlled room temperature of 15-25 °C and protected from light and moisture. Itraconazole oral solution should be stored at 25 °C or lower and should not be frozen.Commercially available itraconazole injection should be stored at 25 °C or lower and protected from lightfreezing should be avoided. Following dilution of itraconazole injection in the 0.9% sodium chloride injection diluent supplied by the manufacturer, itraconazole injections may be stored at 2-8 deg or 15-25 °C for up to 48 hours. The injection should be protected from light during storage, but may be exposed to normal room light during administration.Store in tight, light-resistant container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity. |
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| 정리 방법 | 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. |
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| 처리 방법 | 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. |
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| Preventive Measures | 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. |
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| Personal Protective Equipment (PPE) | 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. |
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| 상호 작용 | 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. |
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| Hepatotoxicity | 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. |
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| 환경 거동 | 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). |
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| 유해 작용 | While itraconazole is a relatively safe medication, there are some adverse side effects associated with its use. Cardiotoxicity is a rare adverse effect. Itraconazole can decrease heart contractility and left ventricular ejection fraction. The risk of cardiotoxicity increases with a dose greater than 400 mg/day. While most patients' heart function improves after discontinuing itraconazole, some require a transplant. Another adverse effect is hepatotoxicity, which often presents as a reversible increase in aminotransferase levels. This side effect can be minimized with intermittent or short-term dosing. In patients already being treated for hypertension, itraconazole can cause resistant hypertension. The most common adverse effects are gastrointestinal disturbances, such as nausea, mild diarrhea, vomiting, and abdominal pain. Researchers have reported these side effects in 2% to 39% of patients who have used itraconazole. When itraconazole administration is via the intravenous formulation, there is also a risk of injection site reactions, headache, and rash. |
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| 노출 경로 | The absolute oral bioavailability of itraconazole is 55%, and is maximal when taken with a full meal. |
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| Milk Concentrations | 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. |
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| 독성 요약 | Toxic trough levels for itraconazole are over 3 mcg/mL. There is no specific antidote available.Itraconazole interacts with 14-&alphademethylase, 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. |
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| Soil Adsorption/Mobility | 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). |
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| Human Toxicity Excerpts | /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. |
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| Artificial Pollution Sources | Itraconazole's production and use as a medication(1) may result in its release to the environment through various waste streams(SRC). |
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| Environmental Biodegradation | AEROBIC: Itraconazole biodegradation is not expected to biodegrade in the environment, based on a modeling study indicating a time frame on the order of months and longer(1). |
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| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
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| 신호 어 | Warning |
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| 유해·위험 문구 | 암호 유해·위험 문구 위험 등급 범주 신호 어 그림 문자 P- 코드 H302 |
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