Janssen-Cilag Ltd

Change to section 4.4 - Special warnings and precautions for Use

Wording re-ordered. The only new text is:

Itraconazole should not be used within 2 weeks after discontinuation of treatment with CYP 3A4 inducing agents (rifampicin, rifabutin, phenobarbital, phenytoin, carbamazepine, Hypericum perforatum (St. John´s wort). The use of itraconazole with these drugs may lead to subtherapeutic plasma levels of itraconazole and thus treatment failure.

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

visual disturbances and hearing loss added

Change to section 4.8 - Undesirable Effects

A star added to all the ADRs also referred to in section 4.4 and the following added underneath the table: * see section 4.4.

Change to section 10 - Date of revision of the text

10 December 2010

Change to section 3 - Pharmaceutical form

   (c) Extension line with 2-way stopcock and in-line filter

Change to section 4.2 - Posology and method of administration

This product is supplied with an extension line with a 2-way stopcock and 0.2 μm in-line filter. The dedicated extension line including the in-line filter must be used to ensure the correct administration of the product (see section 6.6).

Change to section 6. 6 - Instructions for use, handling and disposal

Flush procedure before the infusion

Before the infusion, the catheter should be flushed to avoid compatibility problems between residual amounts of other drugs and itraconazole.

-   Fill the extension line provided with the kit containing the 0.2 mm in-line filter with sterile 0.9% sodium chloride solution and connect directly to the indwelling intravenous catheter.

-   Flush the extension line provided with the kit and indwelling intravenous catheter with sterile 0.9% sodium chloride solution.

-    Add the entire volume (25 ml) of Sporanox I.V. concentrate to the bag in a slow single action (up to 60 seconds). During the admixing process some opalescence may appear. This is a normal phenomenon for the product and will disappear after the full content of the 25 ml of Sporanox IV has been diluted into the Sodium Chloride infusion bag and after gentle mixing.. Withdraw needle after injecting the Sporanox IV concentrate into the bag.

-    Gently mix the content of the bag once the Sporanox I.V. concentrate is completely transferred to the bag. The admixture will become clear but product intrinsic aggregates (described as fibrous to flake-like, non-crystalline, white particles) may be observed. These aggregates do not affect the quality of the product.

New diagrams also

Change to section 10 - Date of revision of the text

06 December 2010

Change

eMC - Summary of Change Details Per Section

Change to section 3 – pharmaceutical form

Sporanox IV 10 mg/ml concentrate and solvent ( 0.9% Sodium Chloride Injection) for solution for infusion is presented in a procedure pack consisting of:

(a) 25 ml of Sporanox IV 10 mg/ml concentrate for infusion, a colourless solution presented in a glass ampoule.

(b) 50 ml of 0.9 % Sodium Chloride Injection solvent for solution for infusion, a colourless solution presented in a polypropylene bag.

Change to section 6.1 – List of Excipients

Hydroxypropyl--cyclodextrin

propylene glycol

hydrochloric acid concentrated

sodium hydroxide (for pH adjustment)

water for injections.

Change to section 10 – Date of revision of the text

21 July 2010

Change to section 6.3 – Shelf Life

Sporanox I.V.:

Shelf life as packaged:

2 years

0.9% Sodium Chloride Injection:

24 months

Admixed Solution:

24 hours.

Change to section 6.5 – Nature and Contents of Container

0.9% Sodium Chloride:

Flexible 75ml polypropylene infusion bag, equipped with a flexible inlet and outlet port, and containing 52 to 56ml of 0.9% Sodium Chloride Injection.

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.

X

Change to section 4.8 – Undesirable effects

, Transient or permanent hearing loss

X

Change to section 10 – Date of revision of the text

November 2008

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 6.6 –  Instructions for use, handling and disposal

Updated to provide a more detailed guide on how to use the different components provided and to ensure efficient and effective delivery of this medicine.

Change to section 2 – quantitative and qualitative composition

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

6.3

Shelf life

Update to shelf life of 0.9% Sodium Chloride Injection-This is now 3 years