141. Weight and Dose Dependent Toxicity of Oral Voriconazole in a Hematologic Malignancy Population
Session: Poster Abstract Session: Antimicrobial Stewardship: Adverse Drug Events
Thursday, October 8, 2015
Room: Poster Hall
Posters
  • Vori Poster Final Draft.pdf (194.1 kB)
  • Background:

    Voriconazole (VCZ) is associated with adverse events (AEs) such as visual disturbances, altered mental status (AMS), and abnormal liver tests (LFT). We evaluated VCZ toxicity in hematologic malignancy patients (HMP) examining mg/kg dosing, total dose, and patient weight.

    Methods:

    We retrospectively reviewed HMP including stem cell transplantation (SCT) patients at a cancer center who received oral VCZ for at least 48h and did not receive >48h of intravenous VCZ, from 12/2011 to 01/2015. HMPs were evaluated for VCZ discontinuation or dose alteration due to LFT elevation 5X the upper limit of normal (ULN), AMS or other reason within 6 weeks of VCZ initiation. Patients were analyzed using the following groups: dosing (<4 mg/kg/dose, 4 6 mg/kg/dose, or >6 mg/kg/dose), weight (<75 kg, 75 100 kg, or >100 kg), and dose (≤300 mg/dose or >300 mg/dose).

    Results:

    Eighty-eight patients were identified, of which 58 had a SCT. Seventeen of 88 patients, (19.3%) experienced a defined AE. Abnormal LFT accounted for 8 of 17 (43%), followed by AMS (6/17 35%) and then QtC prolongation (2 of 17) and 1 other. There was no difference between allogeneic SCT (8/58) and HM (9/30) (P=0.36) in terms of AE. Of the 19 deaths, 2 were attributed to fungal infections.

    Table 1 summarizes number AE wither by weight range or weight based dosing. There are no differences in AE profile within any of these groups. Also therapy limiting AE were not seen when patients who received >300 mg/dose (5/25, 20%) vs ≤300 mg/dose (12/63, 19%), p=0.88. Table 2 summarizes VCZ levels gathered from the 88 patients.

    Table 1

    Number With AE

    Evaluated by Weight Group

    <75Kg

    7/33 (22%)

    75-100Kg

    6/39 (15.4%)

    >100Kg

    4/16 (25%)

    Evaluated by Dosing Group

    <4mg/kg

    10/51 (19.6%)

    4-6mg/kg

    7/36 (19.4%)

    >6 mg/kg

    0/1 (0%)

    Table 2

    All Patients

    AE Patients

    VCZ Level Drawn

    50/88 (56.8%)

    10/17 (58.8%)

    VCZ Level Elevated (>5.5 mcg/mL)

    9/50 (18%)

    3/10 (30%)

    Mean VCZ Level (mcg/mL)

    3.60

    4.95

    Median Days VCZ Level Taken After Initiation

    7

    7

    Conclusion:

    Although VCZ has non-linear kinetic over 200mg BID, we found no direct relationship to higher doses and increased toxicity, even in patients over 100Kg or in regards to SCT. As such weight based dosing of VCZ remains an important in management of fungal infections and AE can be prevented with VCZ therapeutic drug monitoring.

    Jeffrey Jansen, Pharm.D.1, James Lewis II, PharmD, FIDSA1 and Graeme Forrest, MBBS, FIDSA2, (1)Pharmacy, Oregon Health and Science University, Portland, OR, (2)Veterans Affairs Portland Health Care System, Portland, OR

    Disclosures:

    J. Jansen, None

    J. Lewis II, Astellas: Consultant , Consulting fee
    Cubist: Consultant , Consulting fee
    Theravance: Consultant , Consulting fee
    Accelerate: Consultant , Consulting fee
    Forest: Consultant , Consulting fee

    G. Forrest, None

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.