In this section
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
Indications-only to be used after consultation with Infectious
· 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
· Occasionally used for antifungal
prophylaxis in some transplant patients.
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
oral BD dosing (NO LOAD); 9 -15 days (HIV and
Healthy volunteers 1).
oral BD dosing (WITH LOAD); approx 7 days
Paediatric oral daily dosing (NO LOAD);
11 days (ALL/ Transplant 3).
LOAD then oral dosing; 48 hours (ICU 'at risk
Suggested trough level for prophylaxis
& treatment is 0.5mcg/mL 5.
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
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
Therapeutic Target: Trough 0.5 mcg/mL
oral dosing without a load - sample between 11-14
oral dosing with a load - sample at 7 -10 days.
· For IV
dosing following published regimen4- sample at 3-5
Analysis is performed at St Vincent's Hospital, Sydney,
Liaise with Clinical Pharmacology and collect sample to
be available by 10:00am, Wednesday.
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:
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:
3. De Repentigny L et al. Repeated-dose
pharmacokinetics of an oral solution of itraconazole in infants and
children. Antimicrob Agents Chemother. 1998 Feb;
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:
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.