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4CPS-112 Voriconazole therapeutic drug monitoring: relationship with liver toxicity
  1. P Taberner Bonastre1,
  2. A Aragones Eroles2,
  3. M Martinez Sogues1,
  4. B Martinez Castro1,
  5. SM Cano Marrón1,
  6. E Rivero Arango3,
  7. S Almacellas Gomez4,
  8. G Cao Baduell2,
  9. M Gilabert Sotoca1,
  10. M Ibarz Escuer2,
  11. JA Schoenenberger Arnaiz1
  1. 1Hospital Universitario Arnau de Vilanova, Hospital Pharmacy, Lleida, Spain
  2. 2Hospital Universitario Arnau de Vilanova, Clinical Analysis, Lleida, Spain
  3. 3Hospital Universitario Arnau de Vilanova, Haematology, Lleida, Spain
  4. 4Hospital Universitario Arnau de Vilanova, Nurse, Lleida, Spain


Background and importance Serious fungal infections are a subject of concern in hospital medicine. Voriconazole is one of the most used antifungal agents to treat these situations. Voriconazole therapeutic drug monitoring (TDM) may help to avoid treatment failures or adverse events.

Aim and objectives This study aimed to evaluate the impact of voriconazole TDM in dose or drug changes and seek a relationship between voriconazole plasma levels and liver toxicity.

Material and methods TDM was performed in patients treated with voriconazole. Plasma levels were measured once a steady state was achieved and immediately before administering the drug (though drug concentration).

Voriconazole concentrations were analysed by a validated reverse phase-high performance liquid chromatography-ultraviolet (RP-HPLC-UV) method.

Liver enzymes and cholestasis markers concentrations (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP) and total bilirubin (TB)), dose, diagnosis, age and sex were registered.

Microsoft Excel was used for the statistics calculation.

Results 68 determinations in 38 patients (73.75% men; aged 64.84 ±11.29 years).

Diagnosis: probable disease 21 (55.28%), possibility 12 (31.57%), prophylaxis 5 (13.15%).

6 (15.8%) patients needed a change in treatment. 5 (83.33%) had the dose changed in order to maintain plasma levels between 1 and 5.5 μg/mL. In 1 patient (16.66%) voriconazole was substituted.

28 (73.7%) started treatment with the dose of 200 mg/12 hours, whereas the rest (26.3%) has a higher dose. 60% of dose changes were in patients taking 200 mg/12 hours.

A positive correlation existed between plasma levels of voriconazole and liver enzymes as well as with cholestasis markers (AST: r2=0.1817; ALT: r2=0.1118; GGT: r2=0.2528; PA: r2=0.2444 and TB: r2=0.4637).

The Chi-square statistic was significant at p<0.05 for plasmatic levels over 3 μg/mL and AST/ALT over physiological range (35 U/L).

The relative risk of presenting ALT over the physiological range is 3.12 and for AST 2.31 in patients with plasmatic levels of voriconazole >3 μg/mL respects the ones whose plasmatic levels were <3 μg/mL.

Conclusion and relevance Voriconazole TDM is a tool that can help to avoid treatment failure and adverse events. Its relationship with liver toxicity, which shows our data, TDM would help to prevent these side effects.

Conflict of interest No conflict of interest

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