Adult

Antifungal Therapeutic Drug Monitoring

  • The table below summarises basic principles of therapeutic drug monitoring (TDM) for antifungal agents.

  • Certain cases may require different monitoring regime when advised by Micro/ID team.

  • All reference ranges are taken from the Bristol Mycology Reference Lab. If a patient sample is sent to another laboratory, these ranges may not be applicable. Discuss with Micro/ID

  • Turnaround time for results is 3–5 working days.

 

There is no evidence for TDM with echinocandins (caspofungin and micafungin) or amphotericin B liposomal (Tillomed/Gilead/AmBisome)

Antifungal agent  TDM recommended

Initial Sample

Target range

(Prophylaxis and Treatment) 

 Repeat levels 
Fluconazole (po/iv)

Not routinely.

Following advice from Micro/ID only. 
Target levels not yet established. May be indicated in rare cases. 
Isavuconazole (po/iv)

Not routinely.

Unclear value in clinical practice. 

Following advice from Micro/ID only. 

Take first level after

5-7 days.

 

IV/PO: pre-dose level (1 hour before administration of next dose)

 

Target levels not yet established.

Pre-dose level: 2-4 mg/L
  • Weekly level until therapeutic.
  • Once in therapeutic range, check level at week 2,4,8,12 then  three monthly.
  • Check level two weeks after any dose change/ addition of new drug/poor compliance/ poor absorption.
  • Linear pharmacokinetics up to 600mg per day.
Itraconazole (po/iv) Yes

Take first level after

5-7 days.

 

IV/PO: pre-dose level (1 hour before administration of next dose)

 

Pre-dose level

Prophylaxis: 0.5–4 mg/L

Treatment: 1-4 mg/L

 

 All pre-dose levels to be kept below 4mg/L to reduce risk of toxicity.
  • Monthly for the first three months then three monthly. (May be checked more frequently if clinically indicated.)
  • Check level two weeks after any dose change/drug interaction/poor compliance/ poor absorption.
Posaconazole (po/iv)

Prophylaxis: Not routinely*

Treatment: Yes

Take first level after

7 days.

 

IV/PO: pre-dose level (taken immediately before administration)

 

Pre-dose level

Prophylaxis: 0.7-3.75mg/L

Treatment: 1-3.75 mg/L

 

All pre-dose levels should be kept below 3.75mg/L to reduce risk of toxicity.
  • Monthly for the first three months then three monthly.
  • Check level 7-14 days after any dose change/drug interaction/poor compliance/ poor absorption
Voriconazole (po/iv)

Prophylaxis: Not routinely*

Treatment: Yes

Take first level after

5-7 days.

 

IV/PO: pre-dose level (taken immediately before administration)

 

Pre-dose level

Prophylaxis and treatment: 1–5.5 mg/L

Bulky or disseminated infections: 2–5.5 mg/L

 

All pre-dose levels to be kept below 5.5mg/L to reduce risk of toxicity.

 
  • Weekly level until therapeutic.
  • Check level 5 days after IV-PO switch.
  • Once in therapeutic range, check level at week 2,4,8,12 then three monthly
  • Check level two weeks after any dose change/drug interaction/poor compliance/ poor absorption
Flucytosine (po/iv)  Yes 

Take first level within initial     72 hours of therapy.

 

Pre-dose (trough) (PO and IV)

AND

Post-dose (peak) level:

PO: 2hours post-dose

IV: 1hour after end of iv infusion

 

Pre-dose level: 20-50 mg/L 

AND

Post-dose level: 50-100 mg/L

 

Pre-dose levels less than 20mg/L have been associated with treatment failure and emergence of resistance.

 

Post-dose levels greater than 100mg/L have been associated with toxicity.

 
  • Check level twice weekly.
  • Check level more often if renal function is not stable.

*TDM recommendation for prophylactic posaconazole or voriconazole in the following cases: 

  • Obesity (BMI over 30kg/m2)
  • Liquid posaconazole
  • GI absorption concerns, especially if prolonged diarrhoea
  • Initiation or stopping of interacting drugs that affect azole metabolism (See BNF or Summary of Product Characteristics for information)
  • Toxicity concerns
  • Suspected poor compliance
  • Dose adjustment

References

  1. Ashbee HR, Barnes RA, Johnson EM, Richardson MD, Gorton R, Hope WW. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology. J Antimicrob Chemother. 2014;69(5):1162-1176. doi:10.1093/jac/dkt508. Accessed on 2024 Jun 06
  2. Mycology reference laboratory handbook  https://www.gov.uk/government/publications/mycology-reference-laboratory-mrl-service-user-handbook/mycology-reference-laboratory-service-user-handbook  Last updated 2023 Mar 16. Accessed on 2024 Jun 06
  3. North Bristol NHS Trust. Severn Pathology: Analytes. https://www.nbt.nhs.uk/severn-pathology/pathology-services/antimicrobial-reference-laboratory/analytes Accessed on 2024 Jun 06 
  4. Schelenz S, Barnes RA, Barton RC, et al. British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases. Lancet Infect Dis. 2015;15(4):461-474. doi:10.1016/S1473-3099(15)70006-X Accessed on 2024 Jun 06
  5. Smith JM, Paul A. Flucytosine. John Hopkins Medicine ABX Guide. Last updated 2017 May 01. Available at: https://www.hopkinsguides.com Accessed on 2024 Jun 06.
  6. Michigan Medicine, University of Michigan. Antifungal Therapeutic Drug Monitoring Recommendations for Adult and Paediatric Patients. Last updated 2023 Dec. Available at: https://www.med.umich.edu/asp/pdf/adult_guidelines/Antifungal_TDM.pdf Accessed on 2024 Jun 06. 

Editorial Information

Last reviewed: 01 Jun 2024