Voriconazole

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Dosing: Adult Antimicrobial Dosing, Non-dialysis

Indication Dosing Notes
All Indications, IV Route 6mg/kg IV Q12h x 2 doses, then 4mg/kg IV Q12hr Risk/benefit consideration for IV formulation for CrCl<50 mL/min, as IV vehicle accumlates; consider PO

All Indications, PO Route

In obese patients consider a weight-based PO regimen (4mg/kg q12H based on adjusted body weight), Consult ID or ASP for assistance. 

 400mg PO Q12h x 2 doses, then 200mg PO Q12* No renal dose adjustment

Dosing: Antimicrobial Dosing in Intermittent & Continuous Hemodialysis

Indication Dosing Notes
All Indications, IV Route 6mg/kg IV Q12h x 2 doses, then 4mg/kg IV Q12hr No dose adjustment in hemodialysis

All Indications, PO Route

In obese patients consider a weight-based PO regimen (4mg/kg q12H ADJ BW), Consult ID or ASP for assistance. 

 400mg PO Q12h x doses, then 200mg PO Q12 No dose adjustment in hemodialysis

Dialysis Notes

Intermittent HD assumes high-flux hemodialysis. CRRT assumes CVVHD with ultrafiltration rate 2L/h and residual native GFR < 10 mL/min.  For detailed view of dialysis dosing and evidence, see Dosing in Hemodialysis document.

Review medications for potential drug interactions.

Voriconazole has high inter- and intra-patient variability.  Voriconazole trough levels should be obtained in most patients, whether receiving the agent for prophylaxis or treatment of fungal infections.  Trough samples should be obtained 3-5 days after: 
-start of therapy
-change in dose
-change in route of administration
-change in potentially interacting drugs

See UCSF Lab Voriconazole Recommendations  for specifics of monitoring.

Note: The manufacturer recommends avoiding IV voriconazole in patients with renal impairment due to potential accumulation of the excipient sulfobutylether-beta-cyclodextrin, which may lead to kidney injury. However, limited data suggest that patients with baseline kidney impairment may safely receive short durations of IV voriconazole (Kim 2016; Lilly 2013; Neofytos 2012; Oude Lashof 2012).

Restricted to ID or Antimicrobial Stewardship except:

1) Prophylaxis against fungal infections on the hematology/BMT/lung/heart transplant services​

2) Suspected or documented serious fungal infection in the hematology/BMT/lung transplant services​

3) Empiric therapy for prolonged febrile neutropenia in hematology/oncology/BMT patient

References:

  1. Kim SH, Kwon JC, Park C, et al. Therapeutic drug monitoring and safety of intravenous voriconazole formulated with sulfobutylether β-cyclodextrin in haematological patients with renal impairment. Mycoses. 2016;59(10):644-651. doi:10.1111/myc.12517
  2. Lilly CM, Welch VL, Mayer T, Ranauro P, Meisner J, Luke DR. Evaluation of intravenous voriconazole in patients with compromised renal function. BMC Infect Dis. 2013;13:14. doi:10.1186/1471-2334-13-14
  3. Neofytos D, Lombardi LR, Shields RK, et al. Administration of Voriconazole in Patients With Renal Dysfunction. Clinical Infectious Diseases. 2012;54(7):913-921. doi:10.1093/cid/cir969
  4. Oude Lashof AML, Sobel JD, Ruhnke M, et al. Safety and Tolerability of Voriconazole in Patients with Baseline Renal Insufficiency and Candidemia. Antimicrob Agents Chemother. 2012;56(6):3133-3137. doi:10.1128/AAC.05841-11