Itraconazole in Allergic Fungal Sinusitis
Itraconazole can be used as adjunctive therapy in allergic fungal sinusitis, but surgery with corticosteroids remains the primary treatment, and the evidence for itraconazole's benefit is weak and inconsistent. 1
Primary Treatment Approach
Surgery (polypectomy and sinus washout) combined with corticosteroids is the cornerstone of AFRS management, not itraconazole. 1 The IDSA guidelines specifically state that oral antifungal therapy using mold-active triazoles should be reserved for refractory infection and/or rapidly relapsing disease, and even then, this approach is only partially effective. 1
Evidence Quality and Limitations
The European Position Paper on Rhinosinusitis (2020) conducted a meta-analysis showing that oral antifungals do not improve symptoms in AFRS and meta-analysis for preventing recurrence was negative. 1 Multiple RCTs demonstrated:
- No difference in symptom scores between itraconazole and control groups 1
- Similar recurrence rates (44% vs 24% in one study, 66.7% vs 75% in another) with no statistical benefit 1
- Only 23-26% of patients had normal mucosa at 6 months regardless of itraconazole use 1
When to Consider Itraconazole
Reserve itraconazole for patients with refractory disease after failed surgery and maximal medical therapy, or those with contraindications to corticosteroids. 1, 2
Dosing Regimens (when indicated):
Standard dosing: 1
- Loading: 200 mg twice daily for 2 days
- Maintenance: 100 mg twice daily for 4-6 weeks minimum
- Pediatric: 5 mg/kg twice daily for 2 days, then 3 mg/kg twice daily
Alternative regimens used in clinical studies: 3, 4
- 100 mg twice daily for 6 months (for recalcitrant disease)
- 300 mg daily tapered over 3 months (for refractory cases)
Monitoring Parameters
Mandatory liver function testing at baseline and monthly intervals while on therapy. 3, 4 In one series, 3 of 23 patients (13%) had to discontinue due to elevated liver enzymes. 4
No therapeutic drug monitoring is specifically recommended in the AFRS guidelines, unlike in invasive aspergillosis or chronic pulmonary aspergillosis. [1-1]
Treatment Duration
4-6 weeks minimum for adjunctive therapy in AFRS. 1 Some studies used 3-6 months for refractory disease. 3, 4
Contraindications and Drug Interactions
Critical drug interactions exist with nonsedating antihistamines (which AFRS patients commonly take), potentially causing QT prolongation and torsades de pointes. 1 Avoid concurrent use of terfenadine, astemizole, or other QT-prolonging agents.
Relative contraindications: 3, 4
- Hepatic dysfunction
- Congestive heart failure
- Pregnancy
Timing: Preoperative vs Postoperative
If itraconazole is used, preoperative administration may be marginally superior to postoperative use for reducing disease burden and extent of surgery, though both showed similar recurrence rates. 5, 6 One RCT showed preoperative itraconazole reduced Lund-Mackay scores (p=0.007) and achieved complete resolution in 15% of patients. 5
Clinical Reality
The evidence does not support routine use of itraconazole in AFRS. 1 The European guidelines concluded with Level 1b evidence that oral antifungals do not improve symptoms, and Level 4 evidence (very weak) that they may reduce inflammation or recurrence. 1
Corticosteroids consistently outperform antifungals: In comparative studies, only 33% of antifungal-alone patients showed benefit, while corticosteroid groups performed best. 1
Recommended Algorithm
- First-line: Endoscopic sinus surgery + topical nasal corticosteroids 1
- Postoperative: Short-course oral corticosteroids (prednisone 1 mg/kg tapered over 6 weeks) + nasal irrigation 1
- Maintenance: Topical nasal corticosteroids (nebulized budesonide superior to sprays) 1
- Refractory/relapsing cases only: Consider itraconazole 100 mg twice daily for 4-6 weeks with monthly LFT monitoring 1, 4
- Contraindication to steroids: Itraconazole 200 mg twice daily for 3 months may provide symptomatic improvement but not complete clearance 2