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Antifungal — Invasive Aspergillosis Pregnancy: Contraindicated — teratogenic; use liposomal amphotericin B for invasive aspergillosis in pregnancy under specialist guidance

Voriconazole

Brand names: VFEND

Adult dose

Dose: Loading: 6 mg/kg IV every 12 hours × 2 doses; maintenance 4 mg/kg IV every 12 hours (or 200 mg oral BD loading-adjusted equivalent)
Route: IV (acute) / Oral (step-down — 200 mg BD)
Frequency: Every 12 hours
Max: 200 mg twice daily (oral); 4 mg/kg every 12 hours (IV)
First-line treatment for invasive aspergillosis (IA), confirmed or probable. Oral bioavailability ~96% — IV to oral switch when appropriate. Therapeutic drug monitoring (TDM) essential — wide inter-patient variability due to CYP2C19 polymorphism.

Paediatric dose

Dose: 7 mg/kg IV every 12 hours (loading and maintenance — children metabolise faster) mg/kg
Route: IV / Oral
Frequency: Every 12 hours
Max: 200 mg BD oral (body weight-dependent)
BNFc: licensed from 2 years. Children have higher clearance — higher mg/kg dose than adults. Specialist paediatric ID/haematology guidance required.

Dose adjustments

Renal

Oral preferred if eGFR <50 mL/min/1.73m² — IV formulation contains sulfobutyl ether beta-cyclodextrin vehicle which accumulates in renal impairment

Hepatic

Reduce maintenance dose to 2 mg/kg every 12 hours in mild-moderate hepatic impairment; avoid in severe impairment

Paediatric weight-based calculator

BNFc: licensed from 2 years. Children have higher clearance — higher mg/kg dose than adults. Specialist paediatric ID/haematology guidance required.

Clinical pearls

  • TDM mandatory: target trough 1–5 mg/L (efficacy) — CYP2C19 polymorphism causes 4-fold variability in plasma levels between poor and ultra-rapid metabolisers; check levels at steady state (day 5)
  • Visual disturbance (photopsia): occurs in ~30% of patients — transient coloured lights/flashes within 30 min of dose; usually resolves; warn patients not to drive at night
  • Phototoxicity: significant concern with long-term use — cumulative UVA damage; strict sun protection; annual dermatology review for skin cancer surveillance
  • Periostitis and fluorosis: fluoride-containing excipient causes bone pain and periosteal new bone formation with prolonged use — check fluoride levels if bone pain develops
  • IV vehicle accumulation: cyclodextrin vehicle accumulates in renal impairment — switch to oral route if eGFR <50 mL/min/1.73m²
  • ESCMID Guidelines: voriconazole is first-line for invasive aspergillosis; isavuconazole is an alternative with fewer visual side effects and fewer drug interactions

Contraindications

  • Hypersensitivity to voriconazole or excipients
  • Co-administration with sirolimus, rifampicin, carbamazepine, rifabutin, ergot alkaloids, long-acting barbiturates

Side effects

  • Visual disturbances (photopsia — coloured flashes, most common; blurred vision)
  • Phototoxicity/photosensitivity (long-term — skin cancer risk)
  • Hepatotoxicity
  • QT prolongation
  • Peripheral neuropathy
  • Hallucinations/encephalopathy
  • Fluorosis and periostitis (long-term)

Interactions

  • Sirolimus — CONTRAINDICATED (dramatically increases sirolimus levels)
  • Rifampicin — CONTRAINDICATED (abolishes voriconazole effect)
  • Warfarin — significant INR elevation (monitor closely)
  • Tacrolimus, ciclosporin — increased immunosuppressant levels
  • Phenytoin — reduced voriconazole levels; monitor TDM

Monitoring

  • Voriconazole trough levels (target 1–5 mg/L — check at day 5)
  • LFTs (weekly)
  • Renal function
  • ECG (QTc)
  • Visual acuity (formal assessment if visual symptoms)
  • Annual dermatology review (long-term)

Reference: BNFc; BNF 90; BNFc; Herbrecht et al. NEJM 2002 (voriconazole vs amphotericin B in IA); ESCMID/ECMM/ERS Aspergillosis Guidelines 2018; NICE; 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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