Itraconazole in dermatology

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Itraconazole
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Itraconazole in dermatology

Mechanism of action

  • Inhibits the CYP-dependent enzyme lanosterol 14α demethlyase leading to inhibition of the conversion of lanosterol to ergosterol >> fungistatic action.

Indications

  • Tinea pedis (moccasin type)/tinea manuum
    • adults:200–400 mg/day × 1 week.
    • children:3–5 mg/kg/day (maximum 400 mg × 1 week).
  • Tinea unguium
    • adults:200 mg/day × 6 weeks (or) 200 mg BID × 1 week/month for 2 consecutive months(fingernails) ;200 mg/day × 12 weeks (or) 200 mg BID × 1 week/month for 3–4 consecutive months(toenails).
    • children: 5 mg/kg/day (<20 kg), 100 mg/day (20–40 kg), 200 mg/day (40–50 kg), (or) 200 mg BID (>50 kg) × 1 week/month for 2 (fingernails) or 3 (toenails) consecutive months.
  • Tinea corporis
    • (extensive, adults):200 mg/day × 1 week.
    • (extensive, children):3–5 mg/kg/day (maximum 200 mg)× 1 week.
  • Tinea capitis
    • (adults):5 mg/kg/day (maximum 400 mg) ×4–8 weeks.
    • (children): 5 mg/kg/day (maximum 500 mg) ×4–8 weeks.
  • Tinea versicolor :
    • 200 mg po daily × 5–7 days.
    • Single 400 mg dose of itraconazole once monthly for 6 months may be useful as prophylaxis for recurrent tinea versicolor.
  • Pityrosporum folliculitis :200 mg/day for 1–3 weeks.
  • Blastomycosis : ( mild to moderate non-CNS disease) : 200–400 mg/day.
  • Histoplasmosis : (immunocompetent hosts with mild to moderate, stable disease) :200–400 mg/day.
  • Aspergillosis :200–400 mg po daily for at least 3 months ( loading dose of 200 mg TID for first 3 days in life-threatening conditions ).
  • Majocchi’s granuloma : 200 mg po twice daily for 1 week per month, for 2 pulses.
  • Oropharyngeal candidiasis : Swish and swallow 200 mg daily for 1–2 weeks.
  • HIV-associated eosinophilic folliculitis :200–400 mg daily.
  • Tinea imbricata .
  • Recurrent candidiasis : 200 mg BID orally once monthly for 6 months \n
  • Chronic mucocutaneous candidiasis.
  • Cutaneous sporotrichosis :100–200 mg/day until clinical recovery (at least 3 months).
  • Chromoblastomycosis :200–400 mg/day for at least 6 months or until cure.

Monitoring

  • Liver function tests:

Side effects

  • Gastrointestinal
    • Diarrhea (5.6%),dyspepsia(4.3%),abdominal pain (2.4%),nausea (2.6%),flatulence (2.2%).
  • Cutaneous
    • Rash (5.6%), pruritus(2.8%),urticaria(1.1%), SJS .
  • Neurologic
    • Headache
  • Hepatic
    • LFT ≥ 2 × upper limit of normal.
  • others
    • Fever, edema, hypokalemia, neutropenia (rarely).

Contraindications

  • Ventricular dysfunction.
  • Hx of cardiac dysfunction (i.e. CHF).
  • Use of contraindicated antiarrhythmics/cardiac drugs.
  • known hypersensitivity to itraconazole.
  • caution if hypersensitive to other azoles.

Interactions

  • Itraconazole is contraindicated with dofetilide, levacetylmethadol (levomethadyl).
  • Drugs that increase gastric pH, such as proton pump inhibitors, antacids and H2 antihistamines, may reduce the absorption of Itraconazole.
  • It also is contraindicated with HMG -CoA-reductase inhibitors such as lovastatin and simvastatin.
  • Itraconazole is contraindicated with benzodiazepines midazolam and triazolam.
  • It is contraindicated calcium channel blocker nisoldipine, and CYP3A4 ergot alkaloids such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine).
  • Phenytoin causes decreased levels of itraconazole.
  • Itraconazole reduces cyclosporine metabolism by inhibiting CYP3A4.
  • Itraconazole is contraindicated with methadone, disopyramide, dronedarone, quinidine, isavuconazole, irinotecan, ivabradine, lurasidone, pimozide, felodipine, ranolazine, eplerenone, cisapride, naloxegol, lomitapide, avanafil, ticagrelor.
  • In patients with varying degrees of renal or hepatic impairment, coadministration of itraconazole with colchicine, fesoterodine, and solifenacin are contraindicated.

Pregnancy and Lactation

  • Pregnancy category C.
  • Itraconazole is excreted in human milk and should be avoided in lactating patients.

Precautions

  • Itraconazole is not recommended with Abnormal LFT.
  • It is not recommended also with Active liver disease .
  • It is not recommended with hx of liver toxicity with other drugs.
  • Itraconazole can cause or exacerbate congestive heart failure.
  • Do not use for the treatment of onychomycosis in patients with ventricular dysfunction.
  • Monitor for sings and symptoms of CHF.
  • Discontinue if signs of neuropathy.
  • Transient or permanent hearing loss reported (concurrent administration of quinidine).
  • Parenteral form is incompatible with most aqueous solutions; use dedicated line, and do not mix with other drugs in any way.

Drug Info

  • Pulse regimen, for the treatment of onychomycosis, may help improving the adverse effects profile compared to the continuous regimen.
  • Although itraconazole absorption is best when the gastric pH is low, its administration with food is more important for achieving high plasma concentrations.
  • Absorption of itraconazole capsules is reduced when gastric acidity reduced; administer capsules with acidic beverage in patients with reduced gastric acidity and do not administer concomitantly with acid suppressive therapy; monitor for response.

Further readings : Itraconazole


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