Fluconazole

USE IF: Candida infections, cryptococcal infection, and mucosal or selected systemic fungal infections in appropriate hosts with source control and an antifungal strategy consistent with local stewardship / ID support. AVOID IF: Uncontrolled QT risk from combination therapy or high-risk substrate where monitoring/mitigation is not possible; relative caution in **severe** hepatic dysfunction per labeling; known triazole/azole allergy without an alternative plan. INDICATION: Candidiasis · Cryptococcal infection · Mucosal fungal disease · (prophylaxis in selected high-risk patients only on pathway).

• Known **hypersensitivity** to fluconazole or the formulation (cross-reactivity patterns may extend to other azoles — verify allergy history and alternatives)
• Concomitant use with drugs that are **contraindicated** due to unmanageable QT/arrhythmia risk when a safer plan cannot be executed (per insert and ECG/medication reconciliation)
• Severe hepatic impairment as an absolute/relative bar depending on product labeling and the clinical scenario—**specialist** direction when in doubt

• Warfarin and other vitamin K antagonists: **INR** rise and bleeding risk—more frequent monitoring and dose response checks when starting, stopping, or changing fluconazole
• Other **QT-prolonging** agents (macrolides, antiarrhythmics, antipsychotics, 5-HT3 antagonists, etc.): additive QT risk — ECG and electrolyte strategy
• CYP substrates with narrow margins (certain statins, calcineurin inhibitors, calcineurin modulators, selected benzodiazepines, some opioids, and others per interaction checker): may need concentration monitoring or **dose** changes—case-by-case, not a blanket “ignore”

- **PO and IV** can be interchanged for many regimens at equivalent **total daily** dose when the patient can take oral therapy and the syndrome allows - **Once-daily** dosing is common (but not universal—some induction/maintenance regimens for cryptococcal disease are not “one QD for everything”) - IV: give per pharmacy compatibility and line policy; do not “speed up” infusions to shortcut monitoring

• Monitor: - **Clinical** response: fever trajectory, sepsis features, and source control - **Liver** panel on prolonged, high, or worrisome courses - **QT** risk: baseline and follow-up ECG in high co-risk, electrolyte-correct, or poly-QT regimens (per local rule) - **Interactions**: INR, immunosuppressant levels, or other targeted tests when co-therapy is narrow-index
• Recheck: - At the expected endpoint for the **indication** (e.g. oral thrush days vs fungemia week+) - Within **24–72h** of major drug additions/subtractions, or with renal function change
• Hold / change therapy if: - **QTc** moves into a prohibitive or unpredictable zone with torsadogenic co-drugs, or you cannot follow safely - **Hepatocellular** injury pattern is clinically important or meets stopping rules - Clinically the patient is deteriorating and another diagnosis or step-up in therapy is more likely (call ID)

- **Oral** absorption is high and predictable in many standard tablets/suspension contexts - **Half-life** is long, supporting QD regimens in many (not all) chronic/maintenance use cases - **Renal** elimination: adjust dose for reduced CrCl to avoid supratherapeutic levels and added toxicity (especially in prolonged prophylaxis/therapy) - **Hepatic** clearance contributes in part; more concerning for DDI (CYP) and hepatotoxicity than for a simple one-line “liver dose”

- Selective inhibition of **fungal** cytochrome P450 14α-demethylase (lanosterol 14-α demethylase) → impaired **ergosterol** synthesis, disrupted fungal membrane, and **fungistatic** / **-cidal** effect depending on organism, site, and exposure