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Triazole Antifungal Pregnancy: Avoid — teratogenic in animal studies; insufficient human data

Voriconazole

Brand names: Vfend

Adult dose

Dose: IV: loading 6 mg/kg every 12h × 2 doses, then 4 mg/kg every 12h. Oral: ≥40 kg: 400 mg BD (day 1) then 200 mg BD. <40 kg: 200 mg BD loading then 100 mg BD
Route: IV infusion (over 1–3h) or oral
Frequency: BD
Max: 4 mg/kg every 12h IV; 400 mg BD oral
For invasive aspergillosis (first-line), candida infections resistant to fluconazole, rare moulds. Oral bioavailability 96% — switch IV to oral when appropriate. IV formulation contains sulfobutyl-ether-beta-cyclodextrin (SBECD) — accumulates in renal failure, use oral route if eGFR <50.

Paediatric dose

Dose: 8 mg/kg
Route: IV or oral
Frequency: BD (maintenance)
Max: 350 mg BD
Concentration: 10 mg/ml
BNF for Children: loading 9 mg/kg IV every 12h × 2 doses (day 1), then maintenance 8 mg/kg IV every 12h (max 350 mg BD). Calculator uses maintenance dose 8 mg/kg. Children 12–14 yr and ≥50 kg: adult doses. TDM mandatory (target trough 1–5.5 mg/L). Source: BNF for Children 2024; ESCMID/ECMM/ERS Aspergillosis Guidelines 2017

Dose adjustments

Renal

IV: avoid if eGFR <50 (SBECD accumulation — use oral). Oral: no dose adjustment required.

Hepatic

Dose reduce in hepatic impairment — hepatically metabolised

Paediatric weight-based calculator

BNF for Children: loading 9 mg/kg IV every 12h × 2 doses (day 1), then maintenance 8 mg/kg IV every 12h (max 350 mg BD). Calculator uses maintenance dose 8 mg/kg. Children 12–14 yr and ≥50 kg: adult doses. TDM mandatory (target trough 1–5.5 mg/L). Source: BNF for Children 2024; ESCMID/ECMM/ERS Aspergillosis Guidelines 2017

Clinical pearls

  • TDM mandatory in paediatrics and recommended in adults — target trough 1–5.5 mg/L
  • Visual disturbances: transient photopsia on initiation — usually resolves within hours; warn patients not to drive for 1h after each dose
  • Sun protection: significant phototoxicity and long-term SCC risk — sunscreen and protective clothing mandatory
  • Oral bioavailability 96% — prefer oral route in stable patients

Contraindications

  • CYP3A4 substrates: sirolimus (contraindicated), terfenadine, astemizole, pimozide, quinidine, rifampicin
  • IV formulation: eGFR <50

Side effects

  • Visual disturbances (photopsia, blurred vision — very common, transient)
  • Photosensitivity and phototoxicity (use sun protection)
  • Hepatotoxicity (monitor LFTs)
  • QT prolongation
  • Hallucinations (rare but reported)
  • Squamous cell carcinoma risk (long-term phototoxicity)
  • Fluorosis and periostitis (prolonged use, paediatric)

Interactions

  • CYP2C19/CYP2C9/CYP3A4 substrate and inhibitor — massive interactions
  • Warfarin — up to 4-fold increase in INR (halve warfarin, close monitoring)
  • Tacrolimus/ciclosporin — levels trebled — reduce dose by 1/3 (tacrolimus) or half (ciclosporin)
  • Statins — increased myopathy risk
  • Rifampicin, carbamazepine, phenytoin — reduce voriconazole efficacy dramatically

Monitoring

  • LFTs (at least weekly during treatment)
  • Trough voriconazole levels
  • ECG (QT interval)
  • Visual assessments
  • Signs of phototoxicity

Reference: BNFc; BNF; ESCMID/ECMM/ERS Aspergillosis Guidelines 2017; IDSA Aspergillosis Guidelines. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.