Pharmacokinetics in children

The study by Groll et al. shows that the pharmacokinetics of itraconazole in suspension, given as a twice-daily dose (5 mg/kg/day in 2 doses) are comparable in children aged > 5 years to those in adults. De Repentigny et al. state that the plasma concentration of itraconazole as a suspension and a once-daily dose of 5 mg/kg/day in children aged 6 months to 12 years (and in particular children < 2 years) is lower than that in adults. Schmitt et al. have also reported a lower plasma concentration of itraconazole (5 mg/kg/day in 2 doses as a suspension) in younger children (2-5 years) when compared to older children (6-12 years). The above-mentioned studies also show that a once-daily dose results in a lower plasma concentration than a twice-daily dose. The half-life of a twice-daily dose in children aged > 5 years is on average 104.2±94 hours and is about twice as long as that for a once-daily dose (56.5±44 hours). The half-lives in children aged 6 months to 2 years and 2–5 years are 47.4±55 hours and 30.6± 25.3 hours respectively (once-daily dose).

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

The incidence of side effects in children is greater than in adults.

The following are very commonly reported in children (>10%): hypertension, coughing, nausea, vomiting, diarrhoea, abdominal pain, fever, inflammation of the mucosa, rash.

Also noted: increased liver enzymes, hypotension, headaches, dizziness and obstipation.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

For the treatment of oral/oesophageal candidiasis, the solution should be kept in the mouth for as long as possible (approx. 20 seconds) before swallowing. To ensure the optimum absorption, the solution should be taken on an empty stomach. It is recommended that food should not be consumed until 1 hour after ingestion. The capsules, however, should be taken during or directly after a meal. It is recommended that the liquid formulation should preferably be used. The liquid formulation is absorbed better and more consistently than the capsules. The plasma concentration should be determined if the capsules are used.

The absorption of itraconazole from capsules can be improved by taking it with a low-pH carbonated drink (e.g. coke)

Diarrhoea was the most commonly reported undesirable effect in clinical trials. This disturbance of the gastrointestinal tract can result in reduced absorption and can shift the microbiological flora in favour of fungal colonization. In these circumstances, discontinuing the treatment should be considered.

Caution is needed in hepatic and renal insufficiency. Do not administer itraconazole intravenously if the glomerular filtration rate is < 30 ml/min. This is because of the presence of hydroxypropyl β-cyclodextrin in this formulation. Regular checks of the hepatic function are recommended.

There are also indications that pulse therapy for onychomycosis and tinea capitis can cause fewer side effects than continuous therapy

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

• ANTIINFECTIVES FOR SYSTEMIC USE
• ANTIMYCOTICS FOR SYSTEMIC USE

ANTIMYCOTICS FOR SYSTEMIC USE

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

References

1. Hartwig NC, et al, Vademecum pediatrische antimicrobiele therapie, 2005
2. de Repentigny L, et al, Repeated-dose pharmacokinetics of an oral solution of itraconazole in infants and children., Antimicrob Agents Chemother., 1998, 42, 404-8
3. Foot AB, et al, Itraconazole oral solution as antifungal prophylaxis in children undergoing stem cell transplantation or intensive chemotherapy for haematological disorders, Bone Marrow Transplant., 1999, 24, 1089-93
4. Ginter-Hanselmayer G, et al, Itraconazole in the treatment of tinea capitis caused by Microsporum canis: experience in a large cohort, Pediatr Dermatol., 2004, 499-502
5. Ginter-Hanselmayer G, et al, Onychomycosis: a new emerging infectious disease in childhood population and adolescents. Report on treatment experience with terbinafine and itraconazole in 36 patients, J Eur Acad Dermatol Venereol, 2008, 22, 470-5
6. Grigull L, et al, Intravenous and oral sequential itraconazole antifungal prophylaxis in paediatric stem cell transplantation recipients: a pilot study for evaluation of safety and efficacy., Pediatr Transplant, 2007, 11, 261-6
7. Groll AH, et al, Safety, pharmacokinetics, and pharmacodynamics of cyclodextrin itraconazole in pediatric patients with oropharyngeal candidiasis., Antimicrob Agents Chemother, 2002, 46, 2554–63
8. Gupta AK, et al, Efficacy and safety of itraconazole use in children, Dermatol Clin, 2003, 21, 521-35
9. Gupta AK, et al, Itraconazole is effective in the treatment of tinea capitis caused by Microsporum canis., Pediatr Dermatol, 2001, 18, 519-22
10. Gupta AK, et al, The use of itraconazole to treat cutaneous fungal infections in children., Dermatology., 1999, 199, 248-52
11. Hennig S, et al, Population pharmacokinetics of itraconazole and its active metabolite hydroxy-itraconazole in paediatric cystic fibrosis and bone marrow transplant patients., Clin Pharmacokinet., 2006, 45, 1099-114
12. Mouy R, et al, Long-term itraconazole prophylaxis against Aspergillus infections in thirty-two patients with chronic granulomatous disease., J Pediatr., 1994, 125, 998-1003
13. Schmitt C, et al, Pharmacokinetics of itraconazole oral solution in neutropenic children during long-term prophylaxis, Antimicrob Agents Chemother., 2001, 45, 1561-4
14. Tobón AM, et al, Disseminated histoplasmosis in children: the role of itraconazole therapy, Pediatr Infect Dis J, 1996, 15, 1002-8
15. CBO, Richtlijn Diagnostiek en behandeling Cystic Fibrosis, www.cbo.nl, 2007

Changes

Therapeutic Drug Monitoring

Overdose