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Antifungal — Triazole (Ophthalmic Compounded Preparation) Pregnancy: Avoid — teratogenic in animal studies; highly toxic to fetus at systemic doses

Voriconazole (Ophthalmic — Fungal Keratitis)

Brand names: VFEND (systemic); Voriconazole 1% eye drops — compounded

Adult dose

Dose: 1 drop of 1% solution every 1–2 hours (acute) reducing to every 4–6 hours as response improves
Route: Topical (ophthalmic — compounded preparation) or oral/IV (systemic for severe cases)
Frequency: Hourly initially; reducing as clinical response achieved
Max: Hourly dosing in acute phase
Voriconazole 1% eye drops are not commercially available — must be prepared by specialist pharmacy (compounded). Oral voriconazole 200 mg BD is used for severe fungal keratitis or fungal endophthalmitis (excellent intraocular penetration). Systemic oral voriconazole achieves therapeutic intraocular levels.

Paediatric dose

Dose: 9 mg/kg
Route: Oral (systemic)
Frequency: Twice daily
Max: 350 mg twice daily
Paediatric systemic voriconazole for severe fungal keratitis — pharmacokinetics highly variable in children; TDM monitoring essential

Dose adjustments

Renal

Topical: no adjustment. Systemic IV: avoid if eGFR <50 mL/min (sulphobutylether-β-cyclodextrin vehicle accumulates). Systemic oral: no dose adjustment for renal impairment

Hepatic

Systemic: Child-Pugh A/B — loading dose standard, halve maintenance dose; Child-Pugh C — use only if benefit outweighs risk

Paediatric weight-based calculator

Paediatric systemic voriconazole for severe fungal keratitis — pharmacokinetics highly variable in children; TDM monitoring essential

Clinical pearls

  • MUTT trial: voriconazole inferior to natamycin for Fusarium keratitis — natamycin should be preferred for filamentous fungi; voriconazole preferred for Candida keratitis and Aspergillus keratitis (better coverage than natamycin in some studies)
  • Systemic oral voriconazole for fungal endophthalmitis: oral bioavailability is 96%; achieves therapeutic vitreous levels; preferred route for fungal endophthalmitis over IV in stable patients
  • Visual disturbances (photopsia, colour changes) are a class effect of systemic voriconazole — occur in up to 30% within 30 minutes of dose; transient, benign, resolve with continued treatment; warn patients before prescribing
  • TDM for systemic voriconazole: trough target 1–5.5 mg/L — CYP2C19 polymorphism causes highly variable pharmacokinetics (poor metabolisers — 15% in Asian populations — have 4× higher levels); TDM is mandatory for prolonged courses
  • Skin cancer risk: prolonged systemic voriconazole use is associated with squamous cell carcinoma and melanoma — annual dermatology review for patients on long-term therapy; strict sun protection

Contraindications

  • Hypersensitivity to voriconazole
  • Concurrent sirolimus, rifampicin, rifabutin, carbamazepine, phenobarbitone, St John's Wort, ergot alkaloids (systemic interactions — major reductions in voriconazole levels)

Side effects

  • Systemic: visual disturbances — photopsia, altered colour vision, blurred vision (up to 30%); transient, dose-related
  • Photosensitivity — avoid sun exposure; skin cancer risk with prolonged systemic use
  • Hepatotoxicity — monitor LFTs
  • QTc prolongation
  • Hallucinations and encephalopathy
  • Topical: burning, stinging

Interactions

  • CYP2C19, CYP2C9, CYP3A4 substrate AND inhibitor — extensive interactions; voriconazole inhibits metabolism of warfarin (2–4× INR increase), ciclosporin, tacrolimus, phenytoin, statins
  • Rifampicin — reduces voriconazole levels by 96%; ABSOLUTE CONTRAINDICATION
  • Omeprazole — CYP2C19 competition — increases voriconazole levels; reduce voriconazole dose by 50%

Monitoring

  • LFTs weekly for first month (systemic)
  • Voriconazole trough levels (TDM — systemic use)
  • QTc (systemic)
  • Slit-lamp keratitis response
  • Visual acuity

Reference: BNFc; BNF 90; MUTT Trial (NEJM 2012); RCOphth Microbial Keratitis Guidelines; ECMM/ISHAM Fungal Keratitis Guidelines; SPC VFEND. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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