이트라코나졸은 합성된 고친유성 경구용 트리아졸계 항진균제로, 수의학에서 전신성 진균증(아스페르길루스증, 크립토코쿠스증, 분아균증, 히스토플라스마증 등) 및 표재성 피부사상균증과 말라세지아 감염 치료에 널리 사용됩니다.
**임상적 진주 및 약리학적 프로파일:**
* **우수한 효능:** 케토코나졸과 같은 구형 이미다졸계보다 효능이 더 뛰어나며, 포유류의 호르몬 합성을 크게 억제하지 않아 내분비계 부작용이 적습니다.
* **조직 분포:** 친유성 및 친각질성이 매우 높아 피부, 피지, 농에 고농도로 축적되므로 피부 진균 감염에 탁월한 효과를 보입니다.
* **제형의 중요성:** 이트라코나졸의 흡수는 제형에 크게 의존합니다. 시판되는 캡슐제는 최적의 흡수를 위해 산성 위 환경과 음식물이 필요합니다. 시판 경구용 액제는 용해도를 높이기 위해 시클로덱스트린을 함유하고 있으며 공복 상태에서 가장 잘 흡수됩니다.
* **조제 경고:** 벌크 분말을 이용한 임의 조제(Compounding)는 강력히 권장하지 않습니다. 이는 종종 혈중 농도를 치료 수준 이하로 떨어뜨리거나 측정 불가능하게 만들어 전신성 진균 감염 시 치명적일 수 있습니다.
작용 기전: Itraconazole is a fungistatic triazole.
**Mechanism of Action:**
* **Enzyme Inhibition:** Itraconazole selectively inhibits the fungal cytochrome P450-dependent enzyme **lanosterol 14α-demethylase**.
* **Pathway Disruption:** This inhibition blocks the conversion of lanosterol to **ergosterol** (the primary sterol in fungal cell membranes) → leads to the accumulation of toxic 14α-methylsterols.
* **Membrane Permeability:** The lack of ergosterol alters the cellular membrane structure → increases membrane permeability → allows leakage of cellular contents and impairs the uptake of purine and pyrimidine precursors.
* **Immunomodulation:** Itraconazole also exhibits mild immune-suppressing activity, likely via the suppression of T-lymphocyte proliferation.
동물 종별 용량
Cats
Histoplasmosis · 10 mg/kg daily PO · PO · q24h · At least 2-4 months · Given with food. Can also be divided twice daily.
Cryptococcosis · 50-100 mg per cat per day PO · PO · q24h · Many months (mean 8.5 months) · If response inadequate, may add flucytosine.
Blastomycosis · 10 mg/kg PO once a day or divided twice a day · PO · q24h or q12h · 2-3 months or until active disease is not apparent · Cats usually require longer treatment than dogs.
Coccidiomycosis · 5-10 mg/kg PO once daily · PO · q24h · 6-12 months
Sporotrichosis · 5-10 mg/kg once daily · PO · q24h · 30 days beyond complete resolution of detectable lesions
Cryptococcosis (mild to moderate, no CNS involvement) · Cats <= 3.5 kg: 50 mg PO once daily or 100 mg PO every other day; Medium/large cats: 100 mg PO once daily · PO · q24h or q48h · 3-12 months · Give with food. Monitor ALT. Continue until completely normal, then check antigen titer.
Coccidioidomycosis · 25-50 mg (total dose) per cat q12-24h · PO · q12-24h
Generalized dermatophytosis (Microsporum canis) · 5 mg/kg PO once daily preferably between meals for 7 days on, 7 days off; repeat 3 times · PO · q24h (pulse) · 5 weeks (treated weeks 1, 3, 5)
Generalized dermatophytosis (Alternative) · 5 mg/kg PO twice daily or 10 mg/kg · PO · q12h or q24h · Generally 3-5 weeks · Give with food. Give until culture is negative 2 times at two week intervals.
투여 경로
PO
금기
Hypersensitivity to itraconazole or other azole antifungals
Hepatic impairment (relative contraindication)
Achlorhydria or hypochlorhydria (relative contraindication)
Reduced cardiac function (relative, due to potential negative inotropic effects)
Pregnancy
Liver disease (avoid use if present)
이상반응
Anorexia (most common in dogs)
Hepatotoxicity (increased ALT, jaundice)
Ulcerative skin lesions/vasculitis (dogs at high doses)
Limb edema (dogs at high doses)
Erythema multiforme (rare)
Toxic epidermal necrolysis (rare)
Vomiting
Weight loss
Depression (especially in cats and African grey parrots)
Diarrhoea
Anorexia
Salivation
Depression and apathy
Abdominal pain
Hepatic toxicosis
Ulcerative dermatitis
약물 상호작용
Amphotericin B · May be antagonistic against Aspergillus or Candida; clinical importance unclear.
Antacids · May reduce oral absorption of itraconazole; administer itraconazole at least 1 hour before or 2 hours after antacids. · major
Buspirone · Plasma concentrations may be elevated.
Busulfan · Itraconazole may increase levels.
Calcium-channel blockers (amlodipine, verapamil) · Itraconazole may increase levels.
Cisapride · Increased cisapride levels and possibility for toxicity; concurrent use contraindicated in humans. · major
Clomipramine · May decrease metabolism and increase clomipramine levels.
Corticosteroids · May inhibit the metabolism of corticosteroids; potential for increased adverse effects.
Cyclophosphamide · May inhibit metabolism of cyclophosphamide and its metabolites; potential for increased toxicity.
Cyclosporine · Increased cyclosporine levels.
Digoxin · May increase digoxin levels; concurrent use considered contraindicated in humans. · major
모니터링
Clinical Efficacy
Liver function tests (monthly ALT recommended with long-term therapy)
Appetite (anorexia is often the first sign of toxicity)
Physical assessment for ulcerative skin lesions in dogs
Liver enzymes (ALT, AST, ALP, Bilirubin) prior to and during prolonged treatment
Clinical signs of hepatotoxicity (anorexia, vomiting, jaundice)
Resolution of clinical signs and negative fungal cultures
과용량
There is very limited information on acute toxicity.
* **Decontamination:** Giving oral antacids may help reduce absorption. If a large overdose occurs, consider gut emptying and provide supportive therapy.
* **Clearance:** Itraconazole is **not** removed by dialysis.
* **Chronic Toxicity:** In studies, dogs receiving 40 mg/kg PO daily for 3 months demonstrated no overt toxicity.
VetSheet 약물 레퍼런스는 면허 수의 전문가를 위한 임상 의사결정 보조 도구이며, 전문적 판단이나 제조사의 최신 라벨을 대신하지 않습니다.
Dermatophyte granuloma · 10 mg/kg PO once daily · PO · q24h · Weeks to months · At least one month beyond clinical resolution and until brush culture is negative x 2.
Dermatophytosis (Pulse therapy) · 5 mg/kg PO once daily on an every other week schedule · PO · q24h (pulse) · Three 'pulses' of one week on, one week off
General use (fungal infections) · 5 mg/kg · PO · q24h · 4-20 weeks of treatment may be needed, dependent upon culture results
Dermatophytosis (Microsporum canis) · 5 mg/kg · PO · q24h · Pulse dosing: 7 days on, 7 days off repeated x3 · Authorized in the form of an oral solution. Used successfully to treat ringworm in Persian cats without the need for clipping.
Horses
Guttural pouch mycosis, mycotic rhinitis or osteomyelitis · 5 mg/kg PO q24h · PO · q24h · Using the oral solution should be sufficient for treatment.
Birds
Fungal infections in Ratites · 6-10 mg/kg PO once daily · PO · q24h · If neuro signs develop reduce dose or discontinue.
Fungal diseases · 5-10 mg/kg PO q12-24h · PO · q12-24h · Use with caution in African grey parrots.
Aspergillosis (Amazon parrots) · 5-10 mg/kg PO once daily · PO · q24h
Aspergillosis (African grey Parrots) · 2.5-5 mg/kg PO once daily · PO · q24h
SmallMammals
Blastomycosis (Mice) · 50-150 mg/kg q24h · PO · q24h
Malassezia dermatitis · 5 mg/kg PO once daily · PO · q24h · 3 weeks · Fair evidence supports recommendation
Pulse therapy for Malassezia dermatitis · 5 mg/kg for 2 consecutive days per week · PO · 2 consecutive days per week · 3 weeks
Dermatophytosis · 5 mg/kg PO once daily · PO · q24h · Prolonged course required · Begin taking cultures after 4 weeks. Continue therapy for 2 weeks beyond clinical cure and when 2-3 negative cultures are obtained at weekly intervals.
Dermatophytosis (Pulse therapy) · 5 mg/kg PO once daily on an every other week schedule · PO · q24h (pulse) · Three 'pulses' of one week on, one week off · Toxicity problems are rare with this protocol.
Blastomycosis · 5 mg/kg PO once daily · PO · q24h · At least 30 days after all signs resolve (total 60-90 days) · Give with food.
Histoplasmosis · 10 mg/kg daily PO · PO · q24h · At least 30 days after all signs resolve (total at least 90 days) · Give with food. If intestinal histoplasmosis, treat with amphotericin B initially.
Blastomycosis (Alternative) · 5 mg/kg PO once a day or divided twice a day · PO · q24h or q12h · 2-3 months or until active disease is not apparent · A loading dose of 10 mg/kg once a day (or divided twice a day) for the first three days may reduce the 'lag' phase.
Coccidiomycosis · 5-10 mg/kg PO once daily · PO · q24h · 6-12 months
Sporotrichosis · 5-10 mg/kg once daily · PO · q24h · 30 days beyond complete resolution of detectable lesions
Pythiosis or lagendiosis (after lesion resection) · 10 mg/kg PO once daily · PO · q24h · At least 2 months after surgery · Given with terbinafine at 5-10 mg/kg PO q24h.
Zygomycosis · 5-10 mg/kg PO q24h · PO · q24h · 3-6 months for non-resectable lesions · After aggressive surgical resection or for non-resectable lesions.
Idiopathic lymphoplasmacytic (chronic) rhinitis (LPR) · 5 mg/kg PO q12h · PO · q12h · Minimum of 3-6 months · Has shown dramatic beneficial improvement in some dogs.
Nasal aspergillosis · 5 mg/kg PO q12h · PO · q12h · 3-6 months · May cure up to 60-70% of dogs, although some studies show marginal efficacy.
Coccidioidomycosis · 5-10 mg/kg PO q24h or 5 mg/kg PO q12h · PO · q24h or q12h
General use (fungal infections) · 5 mg/kg · PO · q24h · 4-20 weeks of treatment may be needed, dependent upon culture results
용량은 면허 수의 전문가를 위한 임상 참고 자료입니다. 항상 최신 라벨과 개별 환자에 대해 확인하십시오.
Limb oedema
Serious cutaneous drug eruptions (occasional)
Dose-related suppression of adrenal function
Fentanyl/Alfentanil · May increase fentanyl or alfentanil levels.