Comprehensive Guide to Itraconazole: Uses, Dosage, Side Effects, and More

What is Itraconazole?

Overview of Itraconazole

Generic Name: Itraconazole

Brand Name: Sporanox, Onmel, generics

Drug Group: Antifungal (triazole)

Commonly Used For

• Treat aspergillosis.
• Manage candidiasis.
• Prevent fungal infections in immunocompromised patients.

Key Characteristics

Form: Oral capsules (100 mg), oral solution (10 mg/mL), IV infusion (200 mg) (detailed in Dosage section).

Mechanism: Inhibits lanosterol 14α-demethylase, depleting ergosterol and damaging fungal membranes.

Approval: FDA-approved (1992 for Sporanox) and EMA-approved for systemic fungal infections.

Indications and Uses of Itraconazole

Itraconazole is indicated for a variety of fungal infections and prophylactic uses, leveraging its broad-spectrum antifungal activity:

Aspergillosis: Treats invasive aspergillosis in immunocompromised patients, reducing mortality, per infectious disease guidelines, supported by clinical trials showing efficacy rates of 60–70%.

Candidiasis: Manages oropharyngeal and esophageal candidiasis, alleviating symptoms in HIV/AIDS patients, recommended in infectious disease protocols with evidence of rapid lesion resolution.

Histoplasmosis: Controls disseminated histoplasmosis, improving survival in endemic areas, with mycology data.

Blastomycosis: Treats pulmonary and extrapulmonary blastomycosis, reducing lesion size, per respiratory medicine studies.

Sporotrichosis: Investigated off-label for cutaneous and lymphocutaneous forms, with dermatology evidence.

Onychomycosis: Manages toenail and fingernail fungal infections, enhancing nail clarity, with podiatry research.

Cryptococcosis: Explored off-label in non-meningeal forms, with infectious disease studies.

Pityriasis Versicolor: Used off-label to treat skin discoloration caused by Malassezia, with dermatology data.

Prophylaxis in Neutropenia: Initiated off-label to prevent invasive fungal infections in neutropenic patients, with oncology evidence.

Zygomycosis (Adjunct): Investigated off-label as an adjunct in refractory cases, with critical care mycology research.

Dosage of Itraconazole

Dosage for Adults

Aspergillosis:

Oral Capsules: 200–400 mg daily (divided into 100–200 mg twice daily) for at least 6–12 weeks.

IV: 200 mg twice daily for 2 days, then 200 mg daily, transitioning to oral after improvement.

Candidiasis (Oropharyngeal/Esophageal):

Oral Solution: 100–200 mg daily (swish and swallow) for 1–2 weeks.

Capsules: 100 mg daily, increased to 200 mg if needed, for 2–4 weeks.

Histoplasmosis:

Oral Capsules: 200 mg once or twice daily for 6–12 months, depending on severity.

Dosage for Children (≥5 years)

Candidiasis or Histoplasmosis (Off-Label):

Oral Solution: 2.5–5 mg/kg/day (max 200 mg/day), divided into two doses, under pediatric infectious disease supervision.

Dosage for Pregnant Women

Pregnancy Category C: Avoid unless benefits outweigh risks; consult an obstetrician and infectious disease specialist, with fetal monitoring.

Dosage Adjustments

Renal Impairment: No adjustment needed for mild cases; avoid IV in severe impairment (CrCl <30 mL/min) due to excipient accumulation.

Hepatic Impairment:

Mild to moderate (Child-Pugh A or B): Reduce dose by 50%; severe (Child-Pugh C): Avoid.

Concomitant Medications: Adjust if combined with CYP3A4 inhibitors (e.g., ketoconazole) or substrates (e.g., statins); monitor for interactions.

Elderly: No specific adjustment; assess liver function and drug clearance.

Prolonged Use: Limit to 6–12 months unless monitored with liver function tests every 2 weeks.

Additional Considerations

• Take this active ingredient with a full meal to enhance absorption (capsules); oral solution should be taken on an empty stomach.
• Avoid antacids or proton pump inhibitors within 2 hours of dosing to prevent reduced bioavailability.

How to Use Itraconazole

Administration:

Oral Capsules: Swallow whole with a meal, taking with a full glass of water.

Oral Solution: Swish in mouth for several seconds and swallow, avoiding food for 2 hours before and after.

IV: Administer over 60 minutes via a central line by a healthcare professional.

Timing: Use at consistent times daily, with capsules taken with food and solution on an empty stomach.

Monitoring: Watch for jaundice, dark urine, or signs of hepatotoxicity (e.g., abdominal pain); report changes immediately.

Additional Tips:

• Store at 15–25°C (59–77°F), protecting from moisture and light.
• Keep out of reach of children; dispose of unused oral solution after 1 month once opened.
• Use a calibrated device for oral solution dosing; avoid grapefruit juice to prevent CYP3A4 inhibition.
• Schedule liver function tests (ALT, AST) every 2–4 weeks during therapy to detect hepatotoxicity early.
• Educate patients on recognizing signs of heart failure (e.g., swelling, shortness of breath) if at risk.

Contraindications for Itraconazole

Hypersensitivity: Patients with a known allergy to Itraconazole or other azoles.

Severe Hepatic Impairment: Contraindicated in Child-Pugh Class C due to hepatotoxicity risk.

Congestive Heart Failure (CHF): Avoid in active or recent CHF due to negative inotropic effects.

Coadministration with Certain Drugs: Contraindicated with CYP3A4 substrates (e.g., cisapride, pimozide) due to QT prolongation risk.

Pregnancy: Avoid in the first trimester unless life-threatening infection is present.

Ventricular Dysfunction: Contraindicated in patients with documented ventricular dysfunction.

Warnings & Precautions for Itraconazole

General Warnings

Hepatotoxicity: Risk of liver injury or failure; monitor LFTs every 2–4 weeks.

Cardiac Effects: Risk of CHF or QT prolongation; assess cardiac function before and during therapy.

Peripheral Neuropathy: Rare risk with prolonged use; monitor for numbness or tingling.

Hypersensitivity Reactions: Risk of anaphylaxis or Stevens-Johnson syndrome; discontinue if severe.

Adrenal Insufficiency: Rare risk with long-term use; monitor cortisol levels.

Additional Warnings

Drug Interactions: Significant risk with CYP3A4 inhibitors or substrates; adjust doses or avoid combinations.

Hearing Loss: Reversible risk with high doses; monitor auditory function.

Pulmonary Toxicity: Rare interstitial lung disease; assess respiratory symptoms.

Renal Impairment: Risk of excipient accumulation with IV use; avoid in severe cases.

Skin Reactions: Rare exfoliative dermatitis; stop if rash worsens.

Use in Specific Populations

Pregnancy: Category C; use only if benefits outweigh risks, with monitoring.

Breastfeeding: Use caution; monitor infant for effects from potential excretion.

Elderly: Higher risk of hepatotoxicity; start with lower doses and monitor closely.

Children: Safe for off-label use with pediatric oversight.

Renal/Hepatic Impairment: Adjust or avoid based on severity.

Additional Precautions

• Inform your doctor about liver disease, heart conditions, or medication allergies before starting this medication.
• Avoid alcohol to reduce hepatotoxicity risk during therapy.
• Use with caution in patients with a history of neuropathy or hearing loss.

Overdose and Management of Itraconazole

Overdose Symptoms

• Nausea, vomiting, or diarrhea.
• Severe cases: Hepatotoxicity, CHF, or QT prolongation with arrhythmias.
• Dizziness, headache, or abdominal pain as early signs.
• Coma or profound hypotension with extremely high doses.

Immediate Actions

Contact the Medical Team: Seek immediate medical help if overdose is suspected.

Supportive Care: Monitor vital signs, provide IV fluids, and manage arrhythmias if needed.

Specific Treatment: No specific antidote; use gastric lavage if recent ingestion and activated charcoal for absorption reduction.

Monitor: Check LFTs, ECG, and cardiac enzymes for 24–48 hours; consult a cardiologist if arrhythmias occur.

Patient Education: Advise against self-adjusting doses and to store safely away from children.

Additional Notes

• Overdose risk is linked to hepatic metabolism; monitor closely in at-risk patients.
• Report persistent symptoms (e.g., yellowing skin, irregular heartbeat) promptly.

Side Effects of Itraconazole

Common Side Effects

• Nausea (10–15%, managed with food)
• Headache (5–10%, relieved with rest)
• Rash (3–8%, decreases with time)
• Abdominal Pain (2–6%, controlled with antacids)
• Dizziness (2–5%, reduced with hydration)

These effects may subside with adaptation.

Serious Side Effects

Additional Notes

Regular monitoring with LFTs (ALT, AST) every 2–4 weeks is essential to detect hepatotoxicity early.

ECG monitoring is recommended in patients with cardiac risk factors or on interacting drugs.

Patients with a history of liver disease should have baseline and follow-up liver biopsies if therapy exceeds 3 months.

Report any unusual symptoms (e.g., swelling, chest pain) immediately to a healthcare provider to address cardiac or hepatic complications.

Long-term use (>6 months) requires audiometry and nerve conduction studies to assess neuropathy and hearing.

Drug Interactions with Itraconazole

This active ingredient may interact with:

• CYP3A4 Substrates: Increases levels (e.g., simvastatin, midazolam); avoid or adjust dose.
• CYP3A4 Inhibitors: Raises Itraconazole levels (e.g., erythromycin); monitor for toxicity.
• Anticoagulants: Enhances bleeding risk (e.g., warfarin); check INR.
• Antacids: Reduces absorption; separate by 2 hours.
• Calcium Channel Blockers: Potentiates hypotension (e.g., verapamil); use cautiously.

Action: Provide your healthcare provider with a complete list of medications.

Patient Education or Lifestyle

Pharmacokinetics of Itraconazole

Absorption: Oral, peak at 2–5 hours; bioavailability enhanced with food (capsules).

Distribution: Volume of distribution ~700 L; 99% protein-bound.

Metabolism: Hepatic via CYP3A4 to hydroxy-itraconazole (active metabolite).

Excretion: Primarily biliary (as metabolites); renal (<0.03% unchanged); half-life 21–64 hours.

Half-Life: 21–64 hours, prolonged with liver impairment.

Pharmacodynamics of Itraconazole

This drug exerts its effects by:

Inhibiting ergosterol synthesis via 14α-demethylase, disrupting fungal cell membranes.

Treating systemic mycoses like aspergillosis and candidiasis over weeks of therapy.

Exhibiting dose-dependent risks of hepatotoxicity and cardiac effects.

Storage of Itraconazole

• Temperature: Store at 15–25°C (59–77°F); protect from moisture and light.
• Protection: Keep in original container, away from heat and humidity.
• Safety: Store in a secure location out of reach of children and pets due to hepatotoxicity risk.
• Disposal: Dispose of unused capsules or solution per local regulations or consult a pharmacist.

Frequently Asked Questions (FAQs)

Q: What does Itraconazole treat?
A: This medication treats fungal infections.

Q: Can this active ingredient cause nausea?
A: Yes, nausea is common; take with food.

Q: Is Itraconazole safe for children?
A: Yes, off-label with supervision.

Q: How is this drug taken?
A: Orally as capsules or solution, or IV, as directed.

Q: How long is Itraconazole treatment?
A: Typically 2–12 weeks, depending on infection.

Q: Can I use Itraconazole if pregnant?
A: Yes, with caution; consult a doctor.

Regulatory Information

This medication is approved by:

U.S. Food and Drug Administration (FDA): Approved in 1992 (Sporanox) for fungal infections.

European Medicines Agency (EMA): Approved for aspergillosis, candidiasis, and other mycoses.

Other Agencies: Approved globally for antifungal therapy; consult local guidelines.

References

1. U.S. Food and Drug Administration (FDA). (2023). Sporanox (Itraconazole) Prescribing Information.
   • Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
2. European Medicines Agency (EMA). (2023). Itraconazole Summary of Product Characteristics.
   • EMA’s comprehensive information on the medication’s indications and precautions in Europe.
3. National Institutes of Health (NIH). (2023). Itraconazole: MedlinePlus Drug Information.
   • NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
4. World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Itraconazole.
   • WHO’s consideration of Itraconazole for fungal infections.
5. Clinical Infectious Diseases. (2022). Itraconazole in Aspergillosis.
   • Peer-reviewed article on Itraconazole efficacy (note: access may require a subscription).