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Dosing of Anti-Fungal agents on CRRT

Dosing of Anti-Fungal agents on CRRT. Timothy E. Bunchman Professor and Director Pediatric Nephrology & Transplantation Children ’ s Hospital of Richmond Virginia Commonwealth Univ. School of Medicine tbunchman@mcvh-vcu.edu pedscrrt@gmail.com www.pcrrt.com.

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Dosing of Anti-Fungal agents on CRRT

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  1. Dosing of Anti-Fungal agents on CRRT Timothy E. Bunchman Professor and Director Pediatric Nephrology & Transplantation Children’s Hospital of Richmond Virginia Commonwealth Univ. School of Medicine tbunchman@mcvh-vcu.edu pedscrrt@gmail.com www.pcrrt.com

  2. What impacts on Drug clearance • Modality of renal replacement therapy • Characteristics of drug

  3. RRT Modalities

  4. 45ml/kg 35ml/kg 10 9 8 EDD CRRT 7 20ml/kg 6 5 4 3 7 2 6 1 5 0 4 3 2 Dialysis Dose Weekly stdKt/V No. of Days/week PD 0.3 0.5 0.7 0.9 1.1 1.3 1.5 eKt/V each dialysis Adapted from Gotch et al. Kidney Int 2000;58:S3-18

  5. D Diffusive Clearance To increase clearance by diffusion, increase dialysate flow rate

  6. Convective Clearance To increase clearance by convection, increase ultrafiltration rate (will require more replacement fluids)

  7. Sieving Coefficients Solute (MW) Convective Coefficient Diffusion Coefficient Urea (60) 1.01 ± 0.05 1.01 ± 0.07 Creatinine (113) 1.00 ± 0.09 1.01 ± 0.06 Uric Acid (168) 1.01 ± 0.04 0.97 ± 0.04* Vancomycin (1448) 0.84 ± 0.10 0.74 ± 0.04** Calcium (protein bound) 0.67 + 0.1 0.61 + 0.07 Cytokines (large) adsorbed minimal clearance *P<0.05 **P<0.01

  8. D. “Known drug characteristics“ • These recommendations made by panel of nephrologists and pharmacists • Based on: • Protein Binding Information • Volume of Distribution • Molecular Weight

  9. Characteristics of antifungals with Vancomycin as a known reference

  10. AmBisome • Clearance of AmBisome in SPAD (single pass albumin dialysis) showed no excessive clearance • Artif Organs 2006, 30: 118-21

  11. Abelcet • CVVHDF vs no CRRT clearance showed no difference in levels of drug • Int J Antimicrob Agents 2103 42:335-42

  12. Voriconazole • Good penetration into the peritoneum but no clearance by PD • Am J Kid Dis 2005 45:162-166 • CVVHDF shows no impact upon drug levels in the face of normal hepatic function • J Antimicrob Chemother 2007 60:1085-1090 • Dose adjustment not needed in CVVH • Ther Drug Monit 2011 33:393-397

  13. Amphotericin B • Not cleared on CVVHDF • If overdose can be cleared with plasmapheresis and high flux HD • Ann Pharmacother 2013 47

  14. Fluconazole • Once steady state obtained no adjustment needed for CVVHF • NDT 2006 21:1019-1023 • In SLED 72% clearance obtained after 6 hours as compared to 34% on Hemodialysis • Int J Antimicrob Agents 2015 45:192-195

  15. Drug Prescribing in Renal Failureedited by George Aronoff et al • Commonly carried text by pharmacists • http://www.kdp-baptist.louisville.edu/renalbook/ • New edition to come out soon • Recommendations for new drugs • IHD and CRRT recommendations • Pediatric recommendations

  16. Summary

  17. Conclusion • Dose antifungal agents normally due to fact that many are hepatically metabolized and not effected by clearance • Many of these meds interact with other meds (e.g. conazoles and P450 enzyme meds such as tacrolimus or cyclosporine)

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