Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Voriconazole

Generic name
Voriconazole
Brand name
ATC Code
J02AC03

Pharmacokinetics in children

Unlike in adults, voriconazole in children exhibits linear pharmacokinetics. This drug is also eliminated more rapidly by children than adults. For this reason, voriconazole is given to children in higher doses than to adults.

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dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

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Available formulations

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Dosages

Treatment of invasive aspergillosis, candidaemia, fluconazole-resistant severe invasive Candida infections, severe fungal infections caused by Scedosporium spp. and Fusarium spp., prophylaxis for invasive fungal infections in HSCT
  • Oral
    • 2 years up to 12 years
      [5]
      • 18 mg/kg/day in 2 doses. Max: 700 mg/day.

      • Start with intravenous therapy. Only consider oral administration after significant clinical improvement has occurred
         ? If the response is insufficient, the daily dose can be increased in steps of 1 mg/kg.
        ? In the event of toxicity, the daily dose can be lowered in steps of 1 mg/kg.
        ? Duration of the procedure depends on the clinical and mycological response, but should be as short as possible.

    • 12 years up to 15 years and < 50 kg
      [5]
      • 18 mg/kg/day in 2 doses. Max: 700 mg/day.

      • Start with intravenous therapy. Only consider oral administration after significant clinical improvement has occurred
         ? If the response is insufficient, the daily dose can be increased in steps of 1 mg/kg.
        ? In the event of toxicity, the daily dose can be lowered in steps of 1 mg/kg.
        ? Duration of the procedure depends on the clinical and mycological response, but should be as short as possible.

    • 12 years up to 15 years and ≥ 50 kg
      [5]
      • Initial dose: 800 mg/day in 2 doses. during the first 24 hours.
      • Maintenance dose: 400 mg/day in 2 doses.
        • If the response is insufficient: increase the daily dose to 600 mg/day
        • If a higher dose is not tolerated, lower the daily dose in steps of 50 mg to 400 mg/day
        • Duration of the procedure depends on the clinical and mycological response, but should be as short as possible.
    • ≥ 15 years and < 40 kg
      [5]
      • Initial dose: 400 mg/day in 2 doses. during the first 24 hours.
      • Maintenance dose: 200 mg/day in 2 doses.
        • If the response is insufficient: increase the daily dose to 300 mg/day
        • If a higher dose is not tolerated, lower the daily dose in steps of 50 mg to 200 mg/day
        • Duration of the procedure depends on the clinical and mycological response, but should be as short as possible.
    • ≥ 15 years and ≥ 40 kg
      [5]
      • Initial dose: 800 mg/day in 2 doses. during the first 24 hours.
      • Maintenance dose: 400 mg/day in 2 doses.
        • If the response is insufficient: increase the daily dose to 600 mg/day
        • If a higher dose is not tolerated, lower the daily dose in steps of 50 mg to 400 mg/day
        • Duration of the procedure depends on the clinical and mycological response, but should be as short as possible.
  • Intravenous
    • 2 years up to 12 years
      [5]
      • Initial dose: 18 mg/kg/day in 2 doses. during the first 24 hours.
      • Maintenance dose: 16 mg/kg/day in 2 doses.
        • If the response is insufficient, the daily dose can be increased in steps of 1 mg/kg.
        • In the event of toxicity, the daily dose can be lowered in steps of 1 mg/kg.
        • Duration of the procedure depends on the clinical and mycological response, but should be as short as possible.
    • 12 years up to 15 years and < 50 kg
      [5]
      • Initial dose: 18 mg/kg/day in 2 doses. during the first 24 hours.
      • Maintenance dose: 16 mg/kg/day in 2 doses.
        • If the response is insufficient, the daily dose can be increased in steps of 1 mg/kg.
        • In the event of toxicity, the daily dose can be lowered in steps of 1 mg/kg.
        • Duration of the procedure depends on the clinical and mycological response, but should be as short as possible.
    • 12 years up to 15 years and ≥ 50 kg
      [5]
      • Initial dose: 12 mg/kg/day in 2 doses. during the first 24 hours.
      • Maintenance dose: 8 mg/kg/day in 2 doses.
        • In cases of toxicity, the daily dose can be lowered to 6 mg/kg/day in 2 doses.
        • Duration of the procedure depends on the clinical and mycological response, but should be as short as possible.
    • ≥ 15 years
      [5]
      • Initial dose: 12 mg/kg/day in 2 doses. during the first 24 hours.
      • Maintenance dose: 8 mg/kg/day in 2 doses.
        • In cases of toxicity, the daily dose can be lowered to 6 mg/kg/day in 2 doses.
        • Duration of the procedure depends on the clinical and mycological response, but should be as short as possible.

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Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

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The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

The profile of undesirable events in paediatric patients is comparable to that in adults. Photosensitivity reactions, elevated liver enzymes, elevated bilirubin concentrations in the blood, rashes and vision disorders are effects that have occurred in children. There have also been post-marketing reports of pancreatitis.

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The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

In cases of renal impairment, cyclodextrins (SBECD) from the IV formulation may accumulate due to reduced renal clearance. There is limited evidence indicating that children’s renal function does not deteriorate further or experience other side effects. It is important to closely monitor serum creatinine levels at all times. In situations involving relevant comorbidities or co-medications that may further deteriorate renal function, consider switching to the oral formulation. [Hoover 2018; Lilly 2013; Muldrew 2005; Shohab 2014; Luke 2010; Walsch 2000]

In children aged 2-12 with malabsorption and a very low bodyweight for their age, the bioavailability may be limited; intravenous administration is recommended in that case.

Phototoxic reactions occur more often in children; In patients at risk, continue to perform dermatological monitoring even after stopping treatment.

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Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

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Antibiotics
J02AA01
Triazole and tetrazole derivatives
J02AC01
J02AC02
Other antimycotics for systemic use
J02AX06
J02AX04
J02AX01
J02AX05

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References

  1. Scott LJ, et al, Voriconazole : a review of its use in the management of invasive fungal infections., Drugs, 2007, 67, 269-98
  2. Steinbach WJ, et al, New antifungal agents under development in children and neonates, Curr Opin Infect Dis., 2005, 18, 484-9.
  3. Walsh TJ, et al, Pharmacokinetics and safety of intravenous voriconazole in children after single- or multiple-dose administration, Antimicrob Agent Chemother, 2004, 48, 2166-2172.
  4. Walsh TJ, et al:, Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children, Pediatr Infect Dis J., 2002, 21, 240-248.
  5. Pfizer Limited, SPC Vfend (EU/1/02/212/025) (rev 37), www.ema.europa.eu
  6. MMI, Online GL. Gelbe Liste Online, Accessed June 28, 2018.
  7. Zentiva, SmPC Voriconazol Zentiva 200 mg Pulver zur Herstellung einer Infusionslösung (95374.00.00), 06/2017
  8. Zentiva, SmPC Voriconazol Zentiva 50 mg, 200 mg Filmtabletten (90571.00.00, 90572.00.00), 03/2016
  9. Pfizer, SmPC VFEND® 40 mg/ml Pulver zur Herstellung einer Suspension zum Einnehmen (EU/1/02/212/026), 01/2017
  10. Pfizer, SmPC VFEND® 200 mg Pulver zur Herstellung einer Infusionslösung (EU/1/02/212/025, EU/1/02/212/027), 01/2017
  11. Aristo, SmPC Voriconazol Aristo® 50 mg, 100 mg, 200 mg Filmtabletten (94355.00.00, 94356.00.00, 94357.00.00), 07/2016
  12. Pfizer, SmPC VFEND® 50 mg, 200 mg Filmtabletten (EU/1/02/212/001-012, EU/1/02/212/013-024), 01/2017
  13. Hoover RK, et al. , Clinical Pharmacokinetics of Sulfobutylether-β-Cyclodextrin in Patients With Varying Degrees of Renal Impairment., J Clin Pharmacol., 2018, Jun;58(6), 814-82
  14. Lilly CM, et al. , Evaluation of intravenous voriconazole in patients with compromised renal function., BMC Infect Dis, 2013, Jan 16;, 13:14
  15. Muldrew KM, et al., Intravenous voriconazole therapy in a preterm infant., Pharmacotherapy, 2005, Jun;25(6), 893-8
  16. Shohab D, et al., Primary renal aspergillosis and xanthogranulomatous pyelonephritis in an immuno-competent toddler, J Coll Physicians Surg Pak., 2014, May;24 Suppl 2, S101-3
  17. Luke DR, et al., Review of the basic and clinical pharmacology of sulfobutylether-beta-cyclodextrin (SBECD)., J Pharm Sci, 2010, Aug;99(8), 3291-301
  18. Walsh TJ, et al., New targets and delivery systems for antifungal therapy., Med Mycol., 2000, 38 Suppl 1, 335-47

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Changes

Changes