Itraconazole

# Itraconazole ## Overview - **Classification**: Triazole antifungal. - **Mechanism**: Inhibits fungal cytochrome P-450-dependent 14-alpha-demethylase, disrupting ergosterol synthesis and fungal cell membrane integrity. ## Primary Indications 1. **Systemic Fungal Infections** - Blastomycosis, histoplasmosis, aspergillosis (non-invasive). 2. **Onychomycosis** - Fingernail and toenail fungal infections. 3. **Oropharyngeal/Esophageal Candidiasis** - For treatment of mucosal candidiasis. ## Adult Dosing ### Standard Dosing **Systemic Fungal Infections (e.g., Blastomycosis, Histoplasmosis, Aspergillosis)** - **Dose**: **200 mg BID** - **Frequency**: Twice daily - **Route**: Oral (capsules or solution) - **Loading Dose (severe cases)**: **200 mg TID** for first 3 days - **Maximum Dose**: **400 mg/day** - **Duration**: 3-6 months or longer, based on clinical response. **Onychomycosis (Toenail)** - **Dose**: **200 mg BID** - **Frequency**: For 1 week per month - **Route**: Oral (capsules) - **Duration**: Repeat pulse for 3 months (total 3 pulses). **Oropharyngeal/Esophageal Candidiasis** - **Dose**: **200 mg QD** - **Frequency**: Once daily - **Route**: Oral (solution preferred for better mucosal contact, or capsules) - **Duration**: 1-2 weeks. ### Dose Adjustments - **Renal Impairment**: CrCl < 30 mL/min: Use with caution. Consider dose reduction by 50% for chronic use. Monitor closely. - **Hepatic Impairment**: Use with caution. Monitor LFTs. Avoid in patients with active liver disease. - **Elderly Patients**: Use with caution. Consider starting at lower end of dosing range due to potential reduced hepatic/renal function. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: Generally **avoided**. - **Special Notes**: Limited data, safety and efficacy not established. Consult infectious disease specialist if absolutely necessary. ### Infants (1-12 months) - **Dose**: **5 mg/kg/day** - **Frequency**: Once or twice daily (divided dose) - **Maximum**: **200 mg/day** - **Special Notes**: Oral solution preferred for better absorption. Limited data, use with caution. ### Children (1-12 years) **Systemic Fungal Infections / Esophageal Candidiasis** - **Dose**: **2.5-5 mg/kg/day** - **Frequency**: Once or twice daily (divided dose) - **Maximum**: **200 mg/dose** or **400 mg/day** - **Special Notes**: Oral solution preferred for better absorption. Capsules should be taken with food/acidic drink. ### Adolescents (13-18 years) - **Dose**: **Adult dosing** often applicable. - **Maximum**: **400 mg/day** ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to itraconazole. - **Absolute**: Co-administration with CYP3A4 substrates that prolong QT interval (e.g., cisapride, dofetilide, dronedarone, lovastatin, simvastatin, triazolam, midazolam). - **Absolute**: Patients with evidence of ventricular dysfunction or history of congestive heart failure (CHF). - **Absolute**: Co-administration with strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine). ### Common Adverse Effects - **Very Common (>10%)**: Nausea, vomiting, abdominal pain, headache. - **Common (1-10%)**: Diarrhea, rash, dizziness, edema, hypokalemia, increased liver enzymes (ALT/AST). - **Serious but Rare**: Congestive heart failure, hepatotoxicity (including hepatic failure), serious dermatologic reactions (SJS), peripheral neuropathy, adrenal insufficiency. ### Key Drug Interactions - **CYP3A4 Substrates (e.g., statins, alprazolam, calcium channel blockers, digoxin, warfarin)**: Itraconazole is a strong CYP3A4 inhibitor; increases substrate levels, leading to toxicity. **Avoid or dose adjust.** - **Acid-Reducing Agents (PPIs, H2-blockers, antacids)**: Decrease gastric acidity, impairing itraconazole **capsule** absorption. **Separate administration or consider oral solution.** - **QT-prolonging Drugs**: Increased risk of life-threatening arrhythmias. **Concomitant use is contraindicated.** - **CYP3A4 Inducers (e.g., rifampin, phenytoin)**: Decrease itraconazole plasma levels, risking treatment failure. **Avoid co-administration.** ## Monitoring & Follow-up - **Before Treatment**: Baseline LFTs (ALT/AST), serum electrolytes (K, Mg), review cardiac history (CHF risk). - **During Treatment**: LFTs (monthly for chronic therapy), electrolytes periodically. Monitor for signs of CHF (edema, dyspnea, rapid weight gain) and hepatotoxicity (jaundice, dark urine). - **Clinical Signs**: Watch for signs of peripheral neuropathy (tingling, numbness). ## Clinical Pearls - 💡 **Capsules vs. Solution**: Capsules need an acidic environment (take with food or acidic beverage). Oral solution has higher bioavailability and should be taken on an empty stomach. - 💡 **Cardiac Risk**: Contraindicated in patients with current or history of congestive heart failure due to negative inotropic effects. - 💡 **Drug Interactions**: Itraconazole has a high potential for significant drug interactions via CYP3A4 inhibition. Always check for interactions. - 💡 **Absorption**: Capsule absorption is variable; therapeutic drug monitoring (TDM) may be useful for serious infections. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.