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.
Adult: 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.
Note: 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).
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).
Pregnancy: Pregnancy Category C (US FDA). Animal studies show teratogenicity. Should not be used for treatment of onychomycosis during pregnancy. Use only for life-threatening systemic fungal infections if the potential benefit justifies the potential risk to the fetus. Effective contraception is required during and for 2 months after therapy in women of childbearing potential.
Driving: May cause dizziness, vertigo, and blurred vision. Patients should be cautioned about operating machinery or driving until they are certain itraconazole does not affect them adversely.
| 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 |