1. Clinical Overview
Itraconazole is a broad-spectrum triazole antifungal agent. It is a synthetic derivative of ketoconazole, with a more favorable safety profile and a wider spectrum of activity. It is fungistatic at low concentrations and fungicidal at higher concentrations against certain fungi. It is highly lipophilic and keratinophilic, allowing it to concentrate in tissues like skin, nails, and lungs, making it effective for systemic and deep-seated mycoses. In India, it is a cornerstone for treating dermatophytoses, systemic fungal infections, and fungal keratitis.
| Onset | Duration | Bioavailability |
|---|---|---|
| Clinical improvement in systemic infections may be seen within 1-2 weeks, but full therapeutic effect for conditions like onychomycosis may take several months due to slow nail growth. | Tissue concentrations persist for weeks after discontinuation due to high lipophilicity and binding to cellular components. For example, therapeutic levels in nails can persist for up to 6 months post-therapy. | Approximately 55% when taken with a full meal. Bioavailability of the capsule formulation is significantly reduced (by up to 30-40%) under fasting conditions. |
2. Mechanism of Action
Itraconazole inhibits the fungal cytochrome P450-dependent enzyme lanosterol 14-α-demethylase. This inhibition blocks the conversion of lanosterol to ergosterol, an essential component of the fungal cell membrane. The depletion of ergosterol and accumulation of methylated sterol precursors disrupts membrane structure and function, increasing membrane permeability, inhibiting fungal growth (fungistatic), and at higher concentrations, causing cell death (fungicidal).
3. Indications & Uses
- Systemic Fungal Infections: Blastomycosis, Histoplasmosis, Aspergillosis (invasive and allergic bronchopulmonary)
- Dermatophytoses: Extensive tinea corporis, tinea cruris, tinea pedis resistant to topical therapy
- Onychomycosis: Fungal infection of toenails and/or fingernails
- Oropharyngeal and Esophageal Candidiasis
- Systemic Candidiasis (non-neutropenic patients)
4. Dosage & Administration
Adult Dosage: Varies by indication. Common regimens: Onychomycosis (Pulse Therapy): 200mg twice daily for 1 week, repeated after a 3-week gap (Fingernails: 2 pulses; Toenails: 3 pulses). Systemic Infections: 200mg once or twice daily. Oropharyngeal Candidiasis: 100mg once daily for 15 days. Esophageal Candidiasis: 100-200mg once daily for 3 weeks.
Administration: Capsules must be taken IMMEDIATELY AFTER A FULL MEAL to ensure maximal absorption. Swallow whole with water. Do not take with antacids, H2 blockers, or PPIs simultaneously; separate administration by at least 2 hours. For patients with achlorhydria, administer with an acidic beverage (e.g., non-diet cola).
5. Side Effects
Common side effects may include:
- Nausea, abdominal pain, dyspepsia
- Headache
- Dizziness
- Rash, pruritus
- Fatigue
- Constipation or diarrhea
- Elevated liver enzymes (asymptomatic)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Rifampicin, Rifabutin | Markedly reduces itraconazole plasma levels (CYP3A4 induction). | Major |
| Phenytoin, Carbamazepine | Reduces itraconazole levels (CYP3A4 induction). Itraconazole may increase levels of these drugs. | Major |
| Lovastatin, Simvastatin | Increased risk of rhabdomyolysis (CYP3A4 inhibition). | Contraindicated |
| Midazolam, Triazolam | Markedly increased sedation and prolonged effect (CYP3A4 inhibition). | Major |
| Warfarin | Enhanced anticoagulant effect; increased INR risk. | Major |
| Digoxin | Increased digoxin levels and risk of toxicity. | Major |
| Protease Inhibitors (e.g., Ritonavir, Saquinavir) | Complex bidirectional interactions; can increase or decrease levels of both drugs. | Major |
| Cyclosporine, Tacrolimus, Sirolimus | Markedly increased immunosuppressant levels and toxicity (nephrotoxicity, neurotoxicity). | Major |
| Quinidine, Dofetilide | Increased risk of QT prolongation and torsades de pointes. | Contraindicated |
| Proton Pump Inhibitors (e.g., Omeprazole) | Significantly reduces itraconazole absorption by increasing gastric pH. | Major |
7. Patient Counselling
- DO take the capsule immediately after a full meal (lunch or dinner).
- DO complete the full course of therapy, even if symptoms improve early.
- DO inform your doctor about all other medicines, including OTC, herbal (St. John's Wort), and supplements.
- DO get baseline and periodic liver function tests as advised.
- DONT take antacids, ranitidine, or omeprazole within 2 hours of taking itraconazole.
- DONT crush, chew, or break the capsule.
- DONT use for bacterial or viral infections.
8. Toxicology & Storage
Overdose: Nausea, vomiting, diarrhea, dizziness, tinnitus, abdominal pain, polyuria. In severe cases, hepatotoxicity, adrenal dysfunction, and hearing loss may occur.
Storage: Store below 30°C, in a cool, dry place. Protect from light and moisture. Keep out of reach of children.