fluconazole: clinical use

Prescribing considerations

• Confirm the likely organism and infection site; obtain cultures and susceptibility results for invasive, recurrent or refractory infection where appropriate.
• Consider intrinsic resistance in Candida krusei and Candida auris and reduced susceptibility in Candida glabrata.
• Review renal and hepatic function, pregnancy potential, QT-risk factors, electrolyte abnormalities and interacting medicines.
• Select a formulation appropriate for swallowing ability, age, excipient tolerability and clinical condition.
• Account for sucrose and sodium benzoate in oral suspensions, lactose in some capsules, and sodium and fluid load with the infusion.

Contraindications and cautions

• Hypersensitivity to fluconazole, related azoles or product excipients
• Product-specific contraindicated combinations with medicines that prolong QT and depend on CYP3A4 metabolism, including cisapride, astemizole, pimozide, quinidine and erythromycin
• Terfenadine is subject to product-specific contraindications and precautions; check the selected product information

Monitoring

• Renal function when treatment is repeated or renal impairment is present
• Liver tests where clinically indicated, with closer review if results become abnormal or hepatic symptoms develop
• Electrolytes and ECG in patients with significant QT or arrhythmia risk
• INR or prothrombin time with coumarin anticoagulants
• Relevant medicine concentrations or toxicity markers with tacrolimus, ciclosporin, phenytoin and other narrow-therapeutic-index substrates
• Clinical and mycological response, particularly where resistant Candida species are possible
• Rash and systemic features suggesting severe cutaneous reactions or DRESS

Clinical pharmacology

Fluconazole inhibits fungal ergosterol synthesis. Oral bioavailability is high and food does not materially affect absorption. It distributes widely, including into cerebrospinal fluid, and is eliminated mainly unchanged through the kidneys. It moderately inhibits CYP2C9 and CYP3A4 and strongly inhibits CYP2C19.

Formulation and product differences

• Capsules should be swallowed whole; selected capsule products contain lactose.
• Oral suspensions require reconstitution and shaking. Products differ in concentration, measuring device, excipients, storage and in-use shelf life, so instructions must be checked before interchange.
• The infusion is a sodium chloride solution and contributes sodium and fluid; this matters in patients needing sodium or fluid restriction.
• Oral and intravenous routes provide comparable systemic exposure, permitting route selection according to clinical condition.

Solution for infusion

Route: Intravenous

Strengths: 2 mg/mL

Capsule

Route: Oral

Strengths: 50 mg, 150 mg, 200 mg