Itraconazole is a broad-spectrum, synthetic triazole antifungal agent. It is a potent inhibitor of ergosterol synthesis, a critical component of fungal cell membranes. It is highly effective against a wide range of dermatophytes, yeasts (including Candida spp.), and molds (including Aspergillus spp.). In the Indian context, it is a first-line oral therapy for systemic and deep-seated fungal infections, as well as extensive dermatophytoses, which are highly prevalent.
Adult: **Systemic Infections (Aspergillosis, Candidiasis, etc.):** 200 mg once daily, increased to 200 mg twice daily in severe/life-threatening infections. Duration varies from weeks to months. **Onychomycosis (Pulse Therapy - Standard in India):** 200 mg twice daily for one week, repeated after a 3-week drug-free interval. Fingernails: 2 pulses. Toenails: 3 pulses. **Dermatophytosis:** 100-200 mg once daily for 1-4 weeks. **Vulvovaginal Candidiasis:** 200 mg twice daily for 1 day.
Note: **MUST be taken immediately after a full meal or with an acidic carbonated beverage (e.g., cola) to ensure optimal absorption.** Capsules should be swallowed whole. Do not crush or chew. For patients on gastric acid suppressants (PPIs, H2 blockers), administer with an acidic beverage and consider monitoring drug levels if possible.
Itraconazole inhibits the fungal cytochrome P450-dependent enzyme lanosterol 14α-demethylase. This inhibition blocks the conversion of lanosterol to ergosterol, a vital sterol 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 cell growth, and ultimately leading to cell death.
Pregnancy: **US FDA Pregnancy Category C.** Animal studies show teratogenicity (skeletal defects). There are no adequate and well-controlled studies in pregnant women. Itraconazole should be used during pregnancy ONLY if the potential benefit justifies the potential risk to the fetus. **Contraindicated for the treatment of onychomycosis in pregnancy.**
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 | Markedly decreases itraconazole plasma levels (CYP3A4 inducer). | Major |
| Isoniazid | Decreases itraconazole plasma levels. | Moderate |
| Phenytoin, Carbamazepine | Decrease itraconazole plasma levels (CYP3A4 inducers). | Major |
| Clarithromycin, Erythromycin | Increase itraconazole plasma levels (CYP3A4 inhibitors). | Moderate |
| Lovastatin, Simvastatin, Atorvastatin | Increased risk of rhabdomyolysis (CYP3A4 substrate). Contraindicated for Lovastatin/Simvastatin. | Major |
| Midazolam, Triazolam | Markedly increased and prolonged sedative effect (CYP3A4 substrate). | Major |
| Warfarin | Potentiates anticoagulant effect; increased INR risk. | Major |
| Digoxin | Increases digoxin levels, risk of toxicity. | Major |
| Cyclosporine, Tacrolimus, Sirolimus | Markedly increases immunosuppressant levels, risk of nephrotoxicity/neurotoxicity. | Major |
| Quinidine, Dofetilide | Increased risk of QTc prolongation and Torsades de Pointes. Contraindicated. | Major |
| Protease Inhibitors (e.g., Ritonavir) | Complex bidirectional interaction; can increase or decrease levels of both drugs. | Major |
| Oral Hypoglycemics (Sulfonylureas) | Potentiates hypoglycemic effect. | Moderate |