Itraconazole Use and Monitoring

  • Capsules                   

    • 90- 100% bioavailability if taken with food.
    • This is REDUCED to 40-50% if taken on an empty stomach.
    • The bioavailability of this formulation is improved if taken with a carbonated cola drink.

    Oral Solution             

    • 55% bioavailability if taken with food (i.e reduced compared with capsules)
    • This is INCREASED to 72% if taken on an empty stomach.

    All recommendations with regards to monitoring are based on an assumption of optimal oral dosing conditions. Note that there is significant INTER- and INTRA- patient variability in itraconazole pharmacokinetics.

    Indications-only to be used after consultation with Infectious Diseases

    ·        Certain invasive fungal infections for which itraconazole is the drug of choice.

    ·        Occasional use for other invasive infections (e.g. aspergillosis) when amphotericin B is unable to be used and/or oral therapy is preferred (e.g. long-term maintenance therapy).

    ·        Occasionally used for antifungal prophylaxis in some transplant patients.

    Dosing regimens

    (Note that IV formulation is not widely available at this time, so the following refers only to oral dosing).

    ·         Usual dose in adults is 200 to 600 mg/day given once or twice daily.  Dose in children is less clear, but usually 5-10 mg/kg/day is required.

    ·        Oral loading dose of up to 200 mg tds can be used for first 3 days.

    ·        Twice daily dosing may reduce gastro-intestinal side effects.

    Time to steady state:

    Adult oral BD dosing (NO LOAD); 9 -15 days (HIV and Healthy volunteers 1).

    Adult oral BD dosing (WITH LOAD); approx 7 days (Cancer/Chemotherapy 2).

    Paediatric oral daily dosing (NO LOAD); 11 days (ALL/ Transplant 3).

    Adult IV LOAD then oral dosing; 48 hours (ICU 'at risk patients' 4).

    Objectives of therapy:

    Suggested trough level for prophylaxis & treatment is 0.5mcg/mL 5.

    There is no universally recognised level for peak concentration, but one study suggested >1mcg/L based on failure to respond to treatment in adult HIV patients with oral candidiasis 6.

    Dosage is usually limited by clinical side effects (usu. gastrointestinal in oral dosing) rather than a particular serum concentration. therefore no requirement for peak monitoring for 'toxicity'.

    Current recommendations for monitoring

    Therapeutic Target: Trough 0.5 mcg/mL

    Sample Time:

    ·         For oral dosing without a load - sample between 11-14 days.

    ·         For oral dosing with a load - sample at 7 -10 days.

    ·         For IV dosing following published regimen4- sample at 3-5 days.

    Analysis is performed at St Vincent's Hospital, Sydney, on Fridays.

    Liaise with Clinical Pharmacology and collect sample to be available by 10:00am, Wednesday.

    Note that the assay performed is only for Itraconazole. The metabolite, Hydroxy-itraconazole, has similar antifungal activity and 2-3 times the plasma concentration of the parent compound.


    1.       Reynes J et al. Pharmacokinetics of Itraconazole (Oral Solution) in Two Groups of Human Immunodeficiency Virus- Infected Adults with Oral Candidiasis. Antimicrob Agents Chemother. 1997; 41: 2554-8.

    2.       Glasmacher A, Hahn C, Molitor E, Marklein G, Sauerbruch T, Schmidt-Wolf IG. Itraconazole through concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl-beta-cyclodextrin oral solution or coated-pellet capsules.Mycoses. 1999; 42: 591-600.

    3.       De Repentigny L et al. Repeated-dose pharmacokinetics of an oral solution of itraconazole in infants and children. Antimicrob Agents Chemother. 1998 Feb; 42: 404-8.

    4.       Vandewoude K, Vogelaers D, Decruyenaere J, Jaqmin P, De Beule K, Van Peer A, Woestenborghs R, Groen K, Colardyn F. Concentrations in plasma and safety of 7 days of intravenous itraconazole followed by 2 weeks of oral itraconazole solution in patients in intensive care units. Antimicrob Agents Chemother 1997 Dec; 41: 2714-8.

    5.       5. Glasmacher A, Hahn C, Leutner C, Molitor E, Wardelmann E, Losem C, Sauerbruch T, Marklein G, Schmidt-Wolf IG Breakthrough invasive fungal infections in neutropenic patients after prophylaxis with itraconazole. Mycoses 1999; 42: 443-51.

    6.       Cartledge JD, Midgely J, Gazzard BG Itraconazole solution: higher serum drug concentrations and better clinical response rates than the capsule formulation in acquired immunodeficiency syndrome patients with candidosis. J Clin Pathol 1997 Jun; 50: 477-80.