Itrapex

Approved Indications

1. Onychomycos

• Treatment of fingernail and toenail onychomycosis caused by dermatophytes (Trichophyton species).

2. Systemic Mycoses

• Blastomycosis: pulmonary and extrapulmonary infections.
• Histoplasmosis: chronic pulmonary and disseminated forms.
• Aspergillosis: chronic pulmonary or invasive aspergillosis in patients who are intolerant of or refractory to amphotericin B.

3. Oropharyngeal and Esophageal Candidiasis

• Treatment in immunocompromised patients or those resistant to first-line therapies.

4. Dermatophytosis (Tinea Infections)

• Severe or refractory infections of the skin and hair, including tinea corporis, tinea cruris, and tinea pedis, when systemic therapy is indicated.

Off-Label / Additional Uses

• Sporotrichosis: cutaneous and lymphocutaneous forms.
• Paracoccidioidomycosis: chronic or disseminated infections.
• Chromoblastomycosis: chronic cutaneous and subcutaneous fungal infections.
• Coccidioidomycosis: pulmonary and disseminated forms.
• Fluconazole-resistant candidiasis: including esophageal and systemic infections.
• Other systemic fungal infections are unresponsive to or intolerant of conventional therapy.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Adults:

• Onychomycosis:
  200 mg once daily for 12 weeks (fingernails) or 200 mg twice daily for 12 weeks (toenails).
• Systemic fungal infections:
  200 mg once or twice daily, depending on infection severity; treatment duration varies (weeks to months).
• Oropharyngeal candidiasis:
  100 mg once daily for 7–14 days.
• Prophylaxis in immunocompromised patients:
  200 mg once daily.

Elderly:

• No specific dose adjustment required; monitor liver function.

Pediatrics:

• Use in children ≥2 years old; dose based on body weight (5 mg/kg/day divided BID). Not recommended in infants.

Special Populations:

• Renal Impairment:
  No dose adjustment required; negligible renal excretion.
• Hepatic Impairment:
  Use with caution in mild to moderate impairment; contraindicated in severe hepatic impairment.

Administration:

• Oral capsules/tablets should be taken with food to enhance absorption.
• Oral solution should be taken on an empty stomach.
• For better efficacy, continuous therapy is important.
• IV formulation is reserved for severe systemic infections.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Itraconazole is a triazole antifungal agent that inhibits the fungal cytochrome P450 enzyme lanosterol 14α-demethylase, which is critical in converting lanosterol to ergosterol, an essential component of the fungal cell membrane. Inhibition leads to depletion of ergosterol and accumulation of toxic methylated sterol precursors, disrupting membrane integrity and function, resulting in increased membrane permeability and fungal cell death or growth inhibition. This broad-spectrum activity affects many pathogenic yeasts and molds.

• Absorption:
  Oral bioavailability varies; capsule absorption is enhanced by food and acidic gastric pH; oral solution is better absorbed on an empty stomach.
• Distribution:
  Extensive tissue distribution with high lipophilicity; concentrates in keratinous tissues (skin, nails). Plasma protein binding ~99%.
• Metabolism:
  Hepatic metabolism predominantly via CYP3A4, producing active metabolite hydroxy-itraconazole.
• Half-life:
  Approximately 24–42 hours; steady state reached in 7–14 days.
• Elimination:
  Primarily via hepatic metabolism with biliary excretion; minimal renal clearance (<1%).

• Pregnancy:
  FDA Category C. Animal studies show fetal harm at high doses; human data limited. Use only if benefits outweigh risks.
• Lactation:
  Excreted in breast milk; potential for adverse effects on the infant. Breastfeeding is generally not recommended during therapy.

• Primary Class: Antifungal Agent
• Subclass: Triazole Antifungal

• Known hypersensitivity to itraconazole or azole antifungals.
• Concomitant use with drugs highly dependent on CYP3A4 metabolism with narrow therapeutic index (e.g., cisapride, quinidine, dofetilide).
• Severe hepatic impairment.
• Congestive heart failure (negative inotropic effects).
• Coadministration with certain statins (simvastatin, lovastatin) due to risk of rhabdomyolysis.

• Hepatotoxicity: Monitor liver function tests regularly; discontinue if significant liver injury occurs.
• Cardiac Effects: Avoid in patients with heart failure or ventricular dysfunction due to potential negative inotropic effect.
• Drug Interactions: Many due to CYP3A4 inhibition; monitor closely.
• QT Prolongation: Use caution with other QT-prolonging agents.
• Hypersensitivity: Rare anaphylaxis and skin reactions reported.
• Neurological: Peripheral neuropathy and dizziness reported rarely.

Common:

• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain.
• Central nervous system: Headache, dizziness.
• Elevated liver enzymes.

Less Common:

• Rash, pruritus.
• Edema.
• Fatigue.

Serious/Rare:

• Hepatotoxicity (hepatitis, liver failure).
• Congestive heart failure exacerbation.
• Anaphylactic reactions.
• QT prolongation and arrhythmias.

Timing:
Adverse effects typically occur within weeks of therapy but may arise anytime.

• Strong CYP3A4 inhibitors or inducers: Affect itraconazole levels significantly.
• Warfarin: Increased bleeding risk; monitor INR.
• Statins (simvastatin, lovastatin): Increased risk of rhabdomyolysis.
• Benzodiazepines (midazolam, triazolam): Increased sedation.
• Digoxin: Increased serum levels.
• CYP3A4 substrates: Potential increased toxicity or decreased efficacy.

Avoid coadministration with cisapride, quinidine, pimozide, dofetilide, and other contraindicated drugs.

• No major recent changes in approved indications.
• Guidelines emphasize itraconazole as a first-line agent for onychomycosis and several systemic mycoses.
• Newer antifungals (e.g., voriconazole, posaconazole) recommended in some invasive fungal infections.
• Safety monitoring and avoidance of harmful drug interactions remain priorities.

• Store oral capsules/tablets at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Oral solution should be stored tightly closed, at room temperature.
• Avoid freezing.
• Keep out of reach of children.