Ravuconazole

• Invasive Fungal Infections:
  Investigational use in invasive candidiasis and invasive aspergillosis, especially in immunocompromised patients.
• Dermatophytosis:
  Effective against tinea pedis, tinea corporis, and tinea cruris.
• Onychomycosis:
  Treatment of toenail and fingernail fungal infections caused by dermatophytes.
• Endemic Mycoses:
  Experimental use in histoplasmosis, blastomycosis, and coccidioidomycosis.
• Off-label/Experimental Uses:
  Active against certain azole-resistant fungal strains including Candida glabrata and Candida auris.

• Adults:
  Oral dose typically 100 mg once daily. Duration varies by indication:
• Onychomycosis: 12 to 24 weeks
• Dermatophytosis: 2 to 4 weeks
• Invasive infections: under clinical trial protocols
• Pediatrics:
  Safety and dosage not established.
• Elderly:
  Same as adult dose; monitor liver function.
• Hepatic Impairment:
  Use with caution; dose adjustment may be necessary.
• Renal Impairment:
  No adjustment needed.
• Administration:
  Take orally with food to enhance absorption.

Ravuconazole inhibits the fungal enzyme lanosterol 14α-demethylase (CYP51), blocking the synthesis of ergosterol, an essential component of fungal cell membranes. This leads to disruption of membrane integrity, increased permeability, and fungal cell death.

• Absorption:
  Oral bioavailability approximately 50–60%, enhanced with food.
• Distribution:
  Widely distributed; high tissue penetration including skin and nails.
• Protein Binding:
  Greater than 99%.
• Metabolism:
  Hepatic via CYP3A4 and other CYP enzymes.
• Half-life:
  Long elimination half-life of approximately 100 to 200 hours.
• Excretion:
  Primarily fecal; minimal renal excretion.

• Pregnancy:
  Category C. Animal studies suggest potential risk; human data insufficient. Use only if benefits outweigh risks.
• Lactation:
  Unknown if excreted in breast milk. Caution advised when administered to nursing mothers.

• Antifungal agent, second-generation triazole.

• Known hypersensitivity to ravuconazole or other azoles.
• Concomitant use with strong CYP3A4 inducers (e.g., rifampin).
• Severe hepatic impairment without monitoring.
• History of QT prolongation or use with QT-prolonging drugs.

• Monitor liver function due to risk of hepatotoxicity.
• Use cautiously in patients with cardiac arrhythmias or electrolyte abnormalities.
• Risk of cross-resistance with other azoles.
• Not established for pediatric use.
• Pregnancy and breastfeeding require careful consideration.

• Common: Nausea, vomiting, abdominal pain, headache, rash.
• Serious: Hepatotoxicity, QT prolongation, hypersensitivity reactions.
• Side effects typically appear within the first few weeks and may be dose-dependent.

• CYP3A4 inhibitors may increase ravuconazole levels.
• CYP3A4 inducers may reduce efficacy.
• Additive QT prolongation with other QT-prolonging drugs.
• May increase plasma concentrations of warfarin, cyclosporine, and tacrolimus.

• Currently in Phase III clinical trials for invasive fungal infections and onychomycosis.
• Shows promise against azole-resistant fungal strains.
• Not yet approved by FDA; under priority review in some countries.
• IV formulations under investigation.

• Store oral capsules at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Do not freeze.
• For investigational IV formulations, store below 25°C, do not freeze, and use sterilely.