itraconazole: clinical use

Prescribing considerations

• Confirm the organism, infection site, susceptibility context and whether the formulation’s licensed indication is met.
• Complete an interaction review before starting and whenever medicines change; clinically significant inhibition can persist after discontinuation.
• Assess cardiac, hepatic and renal history, previous azole hypersensitivity, gastrointestinal absorption risks, pregnancy and breastfeeding status.
• Consider therapeutic drug monitoring for invasive disease, prophylaxis, impaired absorption, unexpected response, toxicity, hepatic impairment or major interactions.
• Paediatric and older-patient evidence is limited; use requires individual benefit–risk assessment.

Contraindications and cautions

• Hypersensitivity to itraconazole or a formulation excipient.
• Oral solution in ventricular dysfunction, including current or previous congestive heart failure, except where the product’s serious or life-threatening infection exception applies.
• Intravenous formulation in severe renal impairment because hydroxypropyl-beta-cyclodextrin is cleared by glomerular filtration.
• Intravenous formulation where sodium chloride injection is contraindicated.
• Pregnancy for non-life-threatening indications.
• Concurrent use with product-specific contraindicated CYP3A4 substrates.

Monitoring

• Liver function and hepatotoxicity symptoms, particularly with pre-existing abnormalities, previous medicine-related liver toxicity or prolonged therapy.
• Renal function during intravenous treatment; monitor serum creatinine closely in mild or moderate renal impairment.
• Heart failure, fluid retention, blood-pressure changes or pulmonary oedema.
• Itraconazole concentrations where clinically indicated.
• ECG and electrolytes with cardiac or QT risk factors or interacting medicines.
• Clinical response, fungal susceptibility, adherence and absorption when improvement is inadequate.

Clinical pharmacology

Itraconazole inhibits fungal 14-alpha-demethylase and ergosterol synthesis. It has non-linear pharmacokinetics, is highly protein bound and is extensively metabolised through CYP3A4. Itraconazole and hydroxy-itraconazole contribute to activity. It strongly inhibits CYP3A4 and P-glycoprotein; the oral solution also inhibits BCRP.

Formulation and product differences

• The oral solution has greater bioavailability than conventional capsules and should not be switched without clinical review.
• The oral solution is taken without food and contains sorbitol, cyclodextrin and propylene glycol; these excipients may matter in young children, hereditary fructose intolerance and other vulnerable groups.
• The intravenous product contains hydroxypropyl-beta-cyclodextrin, propylene glycol and sodium; renal cyclodextrin clearance drives its severe-renal-impairment contraindication.
• The intravenous concentrate must be diluted only with the supplied sodium chloride solvent and administered through the dedicated filtered line.

Solution for infusion

Route: Intravenous

Strengths: 10 mg/mL

Oral solution

Route: Oral

Strengths: 10 mg/mL