Za Pharmacy
Drugs, Supplies and Delivery
Itraconazole
Itraconazole is a versatile antifungal agent for systemic and dermatophyte infections. Its use requires careful monitoring for hepatotoxicity, cardiac effects, and drug interactions. Adherence to dosing guidelines and therapeutic drug monitoring (target trough: 0.5–1 mg/L) ensures efficacy and minimizes toxicity.
Ultragriseofulvin, a microcrystalline formulation of griseofulvin, is an antifungal agent derived from Penicillium griseofulvum. It works by disrupting fungal microtubule function, inhibiting fungal mitosis. Specifically, it binds to fungal microtubules, preventing spindle formation and arresting cell division. Ultragriseofulvin is fungistatic and effective against dermatophytes, including:
- Trichophyton species.
- Microsporum species.
- Epidermophyton floccosum.
Ultragriseofulvin is primarily used for dermatophyte infections of the skin, hair, and nails. Its clinical applications include:
- Tinea Infections:
- Tinea capitis (scalp ringworm): First-line therapy in children.
- Tinea corporis (body ringworm).
- Tinea pedis (athlete’s foot).
- Tinea cruris (jock itch).
- Onychomycosis (nail infections): Less commonly used due to prolonged treatment duration and newer alternatives.
Adults:
- Microsize Formulation: 500 mg daily in single or divided doses.
- Ultramicrosize Formulation: 250–375 mg daily in single or divided doses.
- Duration:
- Tinea corporis/cruris: 2–4 weeks.
- Tinea capitis: 4–6 weeks.
- Onychomycosis: 6–12 months (or longer).
Children:
- Microsize Formulation: 10 mg/kg/day (max 1 g/day).
- Ultramicrosize Formulation: 5–7.5 mg/kg/day (max 750 mg/day).
Special Populations:
- Hepatic Impairment: Avoid in severe liver disease.
- Renal Impairment: No dose adjustment required.
- Common: Nausea, vomiting, diarrhea, headache, dizziness.
- Serious:
- Hepatotoxicity: Elevated LFTs (monitor baseline and periodically).
- Photosensitivity: Severe sunburn with UV exposure.
- Hypersensitivity Reactions: Rash, urticaria, angioedema.
- Neurologic Effects: Peripheral neuropathy (rare, with prolonged use).
- Hematologic Effects: Leukopenia, neutropenia (rare).
- Hepatic Impairment: Avoid in severe liver disease.
- Pregnancy: Category C (teratogenic in animal studies; avoid unless benefits outweigh risks).
- Lactation: Excreted in breast milk; avoid breastfeeding.
- Photosensitivity: Advise patients to avoid direct sunlight and use sunscreen.
- Alcohol: Disulfiram-like reaction (flushing, tachycardia).
Ultragriseofulvin interacts with drugs metabolized by CYP450 enzymes:
- Warfarin: Reduced anticoagulant effect (monitor INR).
- Oral Contraceptives: Reduced efficacy (use alternative contraception).
- Cyclosporine: Reduced levels (monitor and adjust dose).
- Barbiturates: Reduced griseofulvin levels (avoid combination).
- Alcohol: Disulfiram-like reaction (avoid during treatment).
- Generic: Griseofulvin (microsize and ultramicrosize).
- Brand Names: Gris-PEG (ultramicrosize), Grifulvin V (microsize).
Itraconazole, a triazole antifungal, inhibits fungal cytochrome P450-dependent 14α-lanosterol demethylase, blocking ergosterol synthesis. Ergosterol depletion disrupts fungal cell membrane integrity, leading to cell lysis. Itraconazole is fungistatic against most fungi but fungicidal against certain species. It is effective against:
- Dermatophytes: Trichophyton, Microsporum, Epidermophyton.
- Yeasts: Candida albicans, C. glabrata, Cryptococcus neoformans.
- Molds: Aspergillus species.
- Dimorphic Fungi: Histoplasma capsulatum, Blastomyces dermatitidis.
Itraconazole is indicated for:
- Systemic Fungal Infections:
- Aspergillosis: Second-line therapy after voriconazole.
- Histoplasmosis/Blastomycosis: First-line therapy.
- Candidiasis: For fluconazole-resistant strains.
- Dermatophytoses:
- Onychomycosis (nail infections).
- Tinea corporis, cruris, and pedis.
- Prophylaxis:
- In immunocompromised patients (e.g., HIV, chemotherapy).
- Off-Label Uses:
- Allergic bronchopulmonary aspergillosis (ABPA).
- Pityriasis versicolor.
Adults:
- Capsules: 100–200 mg once or twice daily (take with food for better absorption).
- Oral Solution: 200 mg once or twice daily (fasting improves absorption).
- Pulse Therapy for Onychomycosis: 200 mg twice daily for 1 week per month, repeated for 2–3 months.
Children:
- 5 mg/kg/day (oral solution preferred for better bioavailability).
Special Populations:
- Hepatic Impairment: Avoid in severe liver disease (BNF).
- Renal Impairment: No dose adjustment for oral use; avoid IV formulation (due to cyclodextrin excipient).
- Common: Nausea, vomiting, diarrhea, abdominal pain, headache.
- Serious:
- Hepatotoxicity: Elevated LFTs (monitor baseline and periodically).
- Heart Failure: Avoid in patients with ventricular dysfunction.
- Hypokalemia: Due to mineralocorticoid effects.
- Peripheral Neuropathy: Rare, with prolonged use.
- Adrenal Insufficiency: Rare, with high doses.
- Hepatic/Renal Impairment: Monitor LFTs and avoid in severe liver disease.
- Pregnancy: Category C (teratogenic in animal studies; avoid unless benefits outweigh risks).
- Lactation: Excreted in breast milk; avoid breastfeeding.
- Cardiac Conditions: Avoid in patients with heart failure or ventricular dysfunction.
- Drug Interactions: Itraconazole is a CYP3A4 inhibitor and substrate, leading to significant interactions (see below).
Itraconazole interacts with drugs metabolized by CYP3A4:
- CYP3A4 Substrates:
- Statins: Increased risk of myopathy (e.g., simvastatin).
- Benzodiazepines: Prolonged sedation (e.g., midazolam).
- Calcium Channel Blockers: Hypotension (e.g., felodipine).
- CYP3A4 Inducers:
- Rifampicin/Phenytoin: Reduce itraconazole levels (avoid combination).
- QT-Prolonging Drugs:
- Quinolones/Macrolides: Increased risk of arrhythmias.
- Warfarin: Increased INR (monitor closely).
- Digoxin: Increased levels (monitor serum levels).
- Generic: Itraconazole.
- Brand Names: Sporanox (capsules, oral solution), Itrasys (regional variations).
