• High-risk/very-high risk acute lymphoblastic leukaemia (ALL) in intensive treatment phases
• Acute myeloid leukaemia (AML)
• Relapsed acute leukaemia (ALL and AML)
• Allogeneic HSCT with acute Grade II-IV GvHD
• Allogeneic HSCT chronic extensive GvHD
• Severe aplastic anaemia

• Autologous HSCT (neutropenic phase)
• Medulloblastoma (neutropenic phase)

• Non-relapse ALL (excluding HR & VHR ALL in intensive phases)
• Lymphoma (excluding autologous HSCT)
• Solid tumours (excluding autologous HSCT)

• Paediatric solid tumours
• Other brain tumours
• Hodgkin's lymphoma

6-12 mg/kg (max 400 mg) oral/IV daily

oral: round to nearest 50 mg capsules

• Administer with or without food
• Monitor for rash (rare) and hepatotoxicity (rare)
• Monitor for QT prolongation if other risk factors or pro-arrhythmic drugs
• Adjust in renal impairment (speak to pharmacy)

Oral tablets (preferred):

≥13 years OR ≥10 years and ≥30 kg: 300 mg oral daily

Note – Each 100 mg tablet may be dispersed in 10 mL of water. This will take 5–10 minutes to dissolve.

Oral tablet dosing for age <10 years is available. Discuss with CCC pharmacy and ID.

IV (if unable to tolerate/absorb oral tablets):

2–18 years: 6 mg/kg IV daily (max 300 mg)

Trough level >0.7 µg/mL

Take trough level 7 days after starting drug or changing dose or formulation

• Oral suspension is available – however has poor absorption. Only use in consultation with CCC pharmacy and ID
• Monitor hepatotoxicity (rare), neurotoxicity and GI upset
• Monitor for QT prolongation if other risk factors or pro-arrhythmic drugs
• Avoid use when on weekly or fortnightly vinca alkaloids (ie. vincristine). If used, withhold at least 5 days prior to vincristine
• Administer the IV solution via central line only over 90 minutes
• Caution in renal impairment as solubiliser in the intravenous solution may accumulate; consult pharmacy

Oral tablets/suspension:

2 years to <12 years or 12–14 years and weighing <50 kg: 9 mg/kg (max 350 mg) oral BD

≥15 years or aged 12–14 years and weighing ≥50 kg: 200 mg oral BD

Intravenous solution:

2 years to <12 years or 12–14 years and weighing <50 kg: 8 mg/kg (day 1, 9 mg/kg) IV BD

≥15 years or aged 12–14 years and weighing ≥50 kg: 4 mg/kg (day 1, 6 mg/kg) IV BD

Trough level 1–2 µg/mL**

Take trough level 2–5 days after starting drug or changing dose or formulation

• Oral: administer 1 h before or after food (absorption ↓ with high fat meals)
• Counsel on avoidance of sun exposure. Reports of skin cancer with prolonged (>1 yr) use
• Caution in renal impairment as solubilizer may accumulate. Significance is not known; consult pharmacy
• Monitor for rash, hepatotoxicity, neurotoxicity and visual disturbances (NB. a trough level >4 is associated with an increased probability of neurological and ocular toxicity). Visual disturbances are dose related, self-limiting and rarely require cessation of therapy
• Monitor for QT prolongation if other risk factors or pro-arrhythmic drugs

Oral solution (Sporonox®): 2.5 mg/kg oral BD (max 200 mg daily)

Oral solution and capsules are not interchangeable. The oral solution is preferred due to improved bioavailability and as there is limited experience with capsules in children. If conversion is required, consult pharmacy.

Trough level >0.5 µg/mL

Take trough level 10–15 days after starting drug or changing dose

• Itraconazole liquid: administer on an empty stomach at least 1 h before food. Absorption not affected by H2-antagonists
• Note this requires SAS form
• Capsules (Sporanox®): administer with or after food. For patients on gastric acid suppressant medications, separate administration by at least 2 hours and administer with an acidic beverage (e.g. cola)
• Monitor for rash, hepatotoxicity, neurotoxicity and GI upset
• Monitor for QT prolongation if other risk factors or pro-arrhythmic drugs

2–3 mg/kg IV three times per week (max 100 mg daily)

Ambisome is available in 50 mg vials (max 100 mg). Where possible round dose to 50 mg ensuring dose is at least 2 mg/kg (max 100 mg).

• Monitor for renal toxicity, electrolyte disturbances (esp hypokalaemia and hypomagnesaemia) and hepatotoxicity
• Consider pre/concurrent hydration with 10 mL/kg normal saline
• Consider premedication if infusion related adverse effects (inc. fever, chills, rigors)

1–3 months: 25 mg/m² (max 50 mg) IV daily

≥3 months: 50 mg/m² (max 50 mg) IV daily

• May cause histamine induced reaction (rash, facial swelling, pruritus and/or bronchospasm)

• May cause histamine induced reaction (rash, facial swelling, pruritus and/or bronchospasm)

• Confirm true trough sample was taken
• Confirm adherence
• Exclude poor absorption (absorption reduced with severe mucositis and diarrhoea). Depending on agent, diet may also affect absorption (see Table 3)
• Investigate potential drug-drug interactions (see below and discuss with pharmacy)

• Confirm a true trough sample was taken
• Investigate potential drug-drug interactions (see below and discuss with pharmacy)
• If clinical signs of toxicity are not present, consider leaving dose regimen unchanged and monitor potential toxicity carefully

Vinca alkaloid metabolism reduced leading to excess vinca alkaloid exposure.

Cases of neurotoxicity (peripheral neuropathy, autonomic neuropathy and seizures) have been reported with vincristine and vinblastine and itraconazole, voriconazole and posaconazole. Concurrent use with itraconazole leads to earlier and more severe toxicity.

Electrolyte abnormalities, hyponatraemia associated with SIADH and GI upset have also been reported.

Fluconazole is a weaker CYP3A4 inhibitor so toxicity is rare.

Concurrent use of itraconazole is strictly contraindicated. Avoid concurrent use of posaconazole where possible (unless advised by infectious diseases and oncology pharmacy)

For weekly IV vinca alkaloid: non-azole agent is preferred

For monthly IV vinca alkaloid: withhold voriconazole the day before, the day of and the day after vinca alkaloid dose. Monitor for toxicity

If used, withhold posaconazole 5 days prior, the day of and day after vinca alkaloid dose

TKI metabolism reduced, increasing risk of toxicity including QT prolongation and cardiac arrhythmias.

Refer to chemotherapy protocols for detailed management.

Concurrent use of itraconazole, voriconazole and posaconazole is not recommended in most protocols

Fluconazole can be used in most instances except in combination with sorafenib. A non-azole agent is mandated for all patients receiving sorafenib

Bortezomib metabolism reduced.

Cases of new or worsening peripheral neurotoxicity have been reported with itraconazole and voriconazole.

All azoles should be stopped 72 hours prior to bortezomib dosing and recommenced 72 hours (24 hours for fluconazole) after final dose in course. A non-azole agent should be substituted during this period

For example, in patients with AML receiving bortezomib on D1 and D8 in a 28-day course, substitute fluconazole for an echinocandin on D(-3) to D(+12)

Metabolism reduced, leading to significant increases in levels of these drugs.

Reports of significantly increased trough concentrations despite dose reduction, due to combination of itraconazole and sirolimus.

Monitor sirolimus, tacrolimus or cyclosporine levels. Dose reduction usually required

Itraconazole should be used with extreme caution in patients on sirolimus

Use combination with caution. Obtain an ECG prior to starting treatment and weekly thereafter

Azoles should not be used in patients with additional cardiac risk factors including reduced left ventricular fraction and electrolyte disturbances