Itraconazole

Itraconazole (triazole)

  • Pregnancy Category C (low risk)
  • Not routinely recommended during lactation

Formulations

– Tablets, capsules, oral suspension

Dosing

  • Onychomycosis
    • Daily dosing: 200 mg daily x 6-12 weeks
    • Pulse dosing: 200 mg BID x 1 week per month for 3-4 consecutive months 
  • Tinea capitis (children)
    • 5mg/kg (tablets) daily x 4-8 weeks
    • Pulse dosing for tinea capitis: 5 mg/kg daily x 1 week; repeat q month x 2-4 pulses
  • Tinea corporis, tinea pedis & Pityrosporum folliculitis
    • 200 mg daily x 1-2 weeks (2-4 weeks for tinea pedis)
    • Other regimens for tinea pedis: 
      • 100 mg daily x 4 weeks 
      • 400 mg daily x 1 week 
      • 200 mg daily x 2-4 weeks
  • Candida
    • 100 – 200 mg daily
  • Other fungi
    • 200 – 400 mg daily
  • Pityriasis versicolor
    • 200 mg daily for 1 week; prophylaxis: 400 mg one dose monthly x 6 months
  • Seborrheic dermatitis
    • 200 mg daily x 1 week

  • Triazoles inhibit lanosterol 14α demethylase 🡪 ↓ergosterol synthesis (impaired cell wall 🡪 arrested cell growth) (fungistatic)

  • Skin: through passive diffusion (via keratin) & sebum
  • Nails: through nail bed & matrix
  • Hair: via sebum into hair shaft
  • Bioavailability ~ 55% 
  • Half-life 21 hours
  • Capsules/tablets: need acidic pH for absorption, take with food or cola beverage
  • Oral suspension: take on empty stomach
  • Metabolized in liver by CYP3A4
  • Renal (40%) & fecal elimination

FDA

  • – Dermatophyte onychomycosis*, oropharyngeal/esophageal candidiasis (oral solution only), blastomycosis, histoplasmosis, & aspergillosis

    *More effective for Candida onychomycosis

Off-label

  • Other candida & tinea (dermatophyte) infections, pityriasis versicolor, Pityrosporum folliculitis, HIV-associated eosinophilic folliculitis

Absolute

  • Hypersensitivity reaction
  • Congestive heart failure

Relative

  • Prolonged QT
  • Risk factors for liver disease, transaminitis, prior liver insult
  • Renal failure (caution)

  • Pulse treatment may be associated with better side effect profile

Common

  • Headache, gastrointestinal, abnormal liver enzymes, induce congestive heart failure, cardiac arrythmias

Dermatologic

  • Urticaria, angioedema, erythema multiforme, exfoliative dermatitis, Steven Johnson/Toxic epidermal necrolysis, acute generalized exanthematous pustulosis cutaneous small vessel vasculitis, alopecia, photosensitivity, pruritus, hyperhidrosis 

Rare

  • Hepatotoxicity, (transient/permanent), hearing loss, peripheral neuropathy; cytopenias, menstrual disorders

Inhibits CYP3A4 (potent)

  • High risk
    Increase levels of cyclosporine, tacrolimus, statins, benzodiazepines, antipsychotics, dapsone, warfarin, colchicine 

  • Liver function tests before starting treatment (ALT, AST)
  • Symptoms to monitor include nausea, anorexia, fatigue, vomiting, abdominal pain: discontinue & do complete liver profile