Janssen-Cilag Ltd

Change to section 4.8 - Undesirable Effects

Paediatric Population

The safety of SPORANOX oral solution was evaluated in 250 paediatric patients aged 6 months to 14 years who participated in five open-label clinical trials. These patients received at least one dose of SPORANOX oral solution for prophylaxis of fungal infections or for treatment of oral thrush or systemic fungal infections and provided safety data.

Based on pooled safety data from these clinical trials, the very common reported ADRs in paediatric patients were Vomiting (36.0%), Pyrexia (30.8%), Diarrhoea (28.4%), Mucosal inflammation (23.2%), Rash (22.8%), Abdominal pain (17.2%), Nausea (15.6%), Hypertension (14.0%), and Cough (11.2%). The nature of ADRs in paediatric patients is similar to that observed in adult subjects, but the incidence is higher in the paediatric patients.

Change to section 5.1 - Pharmacodynamic Properties

Paediatric Population

The tolerability and safety of itraconazole oral solution was studied in the prophylaxis of fungal infections in 103 neutropenic paediatric patients aged 0 to14 years (median 5 years) in an open‑label uncontrolled phase III clinical study. Most patients (78%) were undergoing allogenic bone marrow transplantation for haematological malignancies. All patients received 5 mg/kg/day of itraconazole oral solution as a single or divided dose. Due to the design of the study, no formal conclusion with regard to efficacy could be derived. The most common adverse events considered definitely or possibly related to itraconazole were vomiting, abnormal liver function, and abdominal pain.

Change to section 5.2 - Pharmacokinetic Properties

Paediatric Population:

Two pharmacokinetic studies have been conducted in neutropenic children aged 6 months to 14 years in which itraconazole oral solution was administered 5 mg/kg once or twice daily. The exposure to itraconazole was somewhat higher in older children (6 to 14 years) compared to younger children. In all children, effective plasma concentrations of itraconazole were reached within 3 to 5 days after initiation of treatment and maintained throughout treatment.

Change to section 10 - Date of revision of the text

21 March 2011

Change to section 4.4 – Special Warnings and Precautions for Use

Hearing Loss

Transient or permanent hearing loss has been reported in patients receiving treatment with itraconazole. Several of these reports included concurrent administration of quinidine which is contraindicated (see sections 4.3 and 4.5). The hearing loss usually resolves when treatment is stopped, but can persist in some patients.

Change to section 4.8 – Undesirable effects

, Transient or permanent hearing loss

Change to section 10 – Date of revision of the text

November 2008

REASON(S) FOR SUBMISSION

Change

eMC - Summary of Change Details Per Section

X

Change to section 4.8 – Undesirable effects

Updated table of undesirable effects

Change to section 5.1 - Pharmacodynamic properties

Updated information on Mode of Action, PK/PD relationship, mechanism of resistance, Breakpoints.

Change to section 10 – Date of revision of the text

October 2007

REASON(S) FOR SUBMISSION

Change

eMC - Summary of Change Details Per Section

X

Change to section 4.2 – Posology and |Method of Administration

Extra Information on Hepatic and Renal impairment

X

Change to section 4.4 – Special Warnings and Precautions for Use

Extra Information on Hepatic and Renal impairment

X

Change to section 5.2 - Pharmacokinetic properties

Extra Information on Special Populations-Hepatic Impairment/ Renal Impairment.

X

Change to section 10 – Date of revision of the text

October 2007

Change to section 2 – quantitative and qualitative composition

Introduction of Sorbitol

Change to section 3 – pharmaceutical form

Changed to: Sporanox oral solution is clear, yellow to slightly amber solution with an odour of cherry.

Change to section 4.4 – Special Warnings and Precautions for Use

New text added related to fructose intolerance:

Sporanox oral solution contains sorbitol and should not be given to patients with rare hereditary problems of fructose intolerance.

Change to section 4.5 –Interaction with other medicinal products and other forms of interaction

Addition of loperamide which should be used with caution, and their plasma concentrations, effects or side effects should be monitored. Their dosage, if co-administered with itraconazole, should be reduced if necessary

Change to section 4.7 - Effects on Ability to Drive and Use Machines

Updated

Change to section 6.1 – List of Excipients

Updated information about excipients

Change to section 6.2 - Incompatibilities

Updated with the following text:  In the absence of compatibility studies this medicinal product must not be mixed with other medicinal products

Change to section 6.5 – Nature and Contents of Container

Minor update

Change to section 9 – Date of Renewal of Authorisation

Updated with last renewal date

Change to section 10 – Date of revision of the text

Updated to Feb 2007

Change to section 1 –Name of the medicinal product

Name Change to Sporanox 10mg/ml Oral Solution

Change to section 2 – quantitative and qualitative composition

Textual change

Change to section 4.2 – Posology and |Method of Administration

Textual change

Change to section 4.3 – Contra-indications

introduction of levacetylmethadol (levomethadyl), sertindole, certain ergot alkaloids, eletriptan and repaglinide, as drugs which are contraindicated with itraconazole.

Wording for contraindication in pregnancy also updated.

Change to section 4.4 – Special Warnings and Precautions for Use

This section has been modified to include the following subheadings: Interaction potential, Use in children, Use in elderly, Hepatic effects, Hepatic impairment, Renal impairment, Neuropathy, Cross hypersensitivity and Cardiac effects.

Change to section 4.5 –Interaction with other medicinal products and other forms of interaction

The significant changes include: the instruction to consult labels of other medicines used concomitantly with itraconazole to determine route of metabolism (Subsection 2. Effect of itraconazole on the metabolism of other drugs), the introduction of levacetylmethadol (levomethadyl), sertindole, certain ergot alkaloids, eletriptan as drugs which are contraindicated with itraconazole.

 The introduction of certain glucocorticoids, cilostazol, disopyramide, halofantrine and repaglinide as drugs that should be used with caution and monitored when coadministered with itraconazole.  In addition, there have been minor textual changes within this section.

Change to section 4.6 – Pregnancy and Lactation

Addition of epidemiological data on exposure to Sporanox and textual changes.

Change to section 4.9 - Overdose

Minor Textual change

Change to section 5.1 - Pharmacodynamic properties

Updated to include in vitro data to support the broad spectrum of itraconazole activity.  In conjunction with this, specific itraconazole-sensitive yeast and fungi are named within this section.  Furthermore, examples of less susceptible Candida species and resistant principal fungus types have also been provided.

Change to section 5.2 - Pharmacokinetic properties

Section 5.2.  Pharmacokinetic Properties includes more up to date and expanded data on the pharmacokinetic properties of itraconazole.  In order to accomodate this increase in data this section has subsequently been reorganised in to subsections titled General pharmacokinetic characteristics, Distribution, Biotransformation, Elimination and Linearity/non-linearity.

Change to section 5.3 - Preclinical Safety Data

Includes mainly textual changes and summary on non-clinical data.

Change to section 10 – Date of revision of the text

December 2006