作用機制: 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.
各物種劑量
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.
給藥途徑
PO
禁忌症
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)
不良反應
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
藥物相互作用
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
監測
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
過量
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.
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
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Limb oedema
Serious cutaneous drug eruptions (occasional)
Dose-related suppression of adrenal function
Fentanyl/Alfentanil · May increase fentanyl or alfentanil levels.