title: Therapeutic Drug Monitoring and Dose Adjustment of Posaconazole Oral Suspension in Adults With Acute Myeloid Leukemia.
abstract: BACKGROUND
  Prophylaxis with posaconazole, an extended-spectrum triazole antifungal, has been shown to increase overall survival in adults with acute myeloid leukemia receiving intensive remission induction chemotherapy. A paucity of data exists evaluating therapeutic drug monitoring and subsequent dose adjustment based on serum concentrations in humans.
  
  
  METHODS
  An observational study was performed in 29 adult patients with acute myeloid leukemia who initially received posaconazole oral suspension 200 mg 3 times daily and required ≥1 dose adjustment because of steady-state posaconazole serum concentration <0.7 mcg/mL. Four dosing schemas were compared simultaneously. Patient records were reviewed to collect patient-related and medication-related factors that may affect serum concentrations.
  
  
  RESULTS
  Thirty-five percent of patients experienced subtherapeutic posaconazole serum concentrations with prophylactic dosing of posaconazole oral suspension. Increasing the dose and/or schedule of posaconazole oral suspension led to attainment of goal posaconazole serum concentrations in all groups. However, patients who received 400 mg orally 3 times daily experienced the least significant increase in serum concentration and remained subtherapeutic, despite doubling the posaconazole daily dose. Toxicities were similar to baseline within all groups. Increasing the dose and/or frequency of posaconazole oral suspension led to an increase in systemic exposure and did not appreciably increase incidence of toxicities.
  
  
  CONCLUSIONS
  Patients receiving posaconazole oral suspension that experience subtherapeutic posaconazole serum concentrations may benefit from increasing the frequency to 200 mg orally 4 times daily or dose to 300 mg orally 3 times daily.
authors.affiliation: *Division of Pharmacy Services, Providence St. Vincent Medical Center, Portland, Oregon; †Division of Pharmacy Services, University of Arizona Medical Center; and ‡Section of Hematology/Oncology, University of Arizona Cancer Center, Tucson.
authors.forename: Shelly E
authors.initials: SE
authors.lastname: Hummert
authors.forename: Myke R
authors.initials: MR
authors.lastname: Green
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D014230:Triazoles / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole