Section 4.8 - Undesirable effects

Thromboembolism may occur very rarely (see section 4.4).

 

 

Vascular disorders

Very rare:       Thomboembolism (both in association with and separate from OHSS)

Section 4.8 Undesirable effects - how to report a side effect - was updated with the addition of Malta. Internal Ref: TW1230178.

4.8 Undesirable effects

 

Ireland

HPRA Pharmacovigilance

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

e-mail: medsafety@hpra.ie

Minor editorial changes, including information on the reporting of adverse reactions in section 4.8.

 

Date change in Section 10

2. Qualitative and QuantitativeComposition

Each

 

multidose vial contains 44 micrograms of follitropin alfa* (equivalent to 600 IU), in order to deliver 33 micrograms (equivalent to 450 IU) in 0.75 ml. Each ml of the reconstituted solution contains 600 IU.
.........

 

10. Date of Revision of the Text

11/2011

The following sections updated:

4. CLINICAL PARTICULARS

4.4 Special warnings and precautions for use

............

Thromboembolic events

In women with recent or ongoing thromboembolic disease or women with generally recognised risk factors for

 

thromboembolic events, such as personal or family history, treatment with gonadotropins may further increase the risk for aggravation or occurrence of such events. In these women, the benefits of gonadotropin administration need to be weighed against the risks. It should be noted however that pregnancy itself as well as OHSS also carry an increased risk of thromboembolic events

 

9. Date of First Authorisation/Renewal of the Authorisation

Date of first authorisation: 20 October 1995

Date of last renewal: 20 October

 

2010

 

10. Date of revision of the text

May 2011

Date of Renewal corrected to:

Date of last renewal: 20 October 2010

Changes to SPC are widespread throughout document as result of MA Renewal. SPC is in compliance with QRD template.

Change to section 7

From:

Serono Europe Ltd.

56 Marsh Wall

London E14 9TP

United Kingdom

To:

Merck Serono Europe Ltd.

56 Marsh Wall

London E14 9TP

United Kingdom

Following changes apply:

4.2     Posology and method of administration

It is advised to adhere to the recommended starting doses indicated below.

Comparative clinical studies have shown that on average patients require a lower cumulative dosage and shorter treatment duration with GONAL-f compared with urinary FSH. Therefore, it is considered appropriate to give a lower total dosage of GONAL-f than generally used for urinary FSH, not only in order to optimise follicular development but also to minimise the risk of unwanted ovarian hyperstimulation. See section 5.1.

5.1     Pharmacodynamic properties

In clinical studies comparing r-hFSH (follitropin alfa) and urinary FSH in assisted reproduction technologies (see table below) and in ovulation induction, GONAL-f was more potent than urinary FSH in terms of a lower total dose and a shorter treatment period needed to trigger follicular maturation.

In assisted reproduction technologies, GONAL-f at a lower total dose and shorter treatment period than urinary FSH, resulted in a higher number of oocytes retrieved when compared to urinary FSH.

 

Table: Results of study GF 8407 (randomised parallel group study comparing  efficacy and safety of Gonal-f with u-FSH in assisted reproduction technologies)

	GONAL-f (n = 130)	u-FSH (n = 116)
No. of oocytes retrieved	11.0 ± 5.9	8.8 ± 4.8
Days of FSH stimulation required	11.7 ± 1.9	14.5 ± 3.3
Total dose of FSH required (no. of FSH 75 IU ampoules)	27.6 ± 10.2	40.7 ± 13.6
Need to increase the dosage (%)	56.2	85.3

Differences between the 2 groups were statistically significant (p<0.05) for all criteria listed.

Section 2 Qualitative and Quantitative Composition: Text amended to include: Excipients: 30 mg sucrose, 1.11 mg disodium phosphate dihydrate, 0.45 mg sodium dihydrogen phosphate monohydrate.

 

For a full list of excipients, see section 6.1.

 

Section 3 Pharmaceutical Form: pH added.

 

Section 4.2 Posology and method of administration: The phrase: ‘….treatment should be stopped and hCG withheld (see warnings)’ has been amended to ‘…treatment should be stopped and hCG withheld (see section 4.4)’.

 

Section 4.4 Special warnings and precautions for use: The following warnings have been added:

 

‘As GONAL-f multidose is intended for several injections, clear instructions should be provided to the patients to avoid misuse of the multidose presentation.’

 

‘Patients with porphyria or a family history of porphyria should be closely monitored during treatment with GONAL-f. Deterioration or a first appearance of this condition may require cessation of treatment.’

 

‘GONAL-f contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.’

 

‘Very rarely, severe OHSS may be complicated by pulmonary embolism, ischemic stroke and myocardial infarction.’

 

The phrase: ‘….the incidence of ovarian hyperstimulation and multiple pregnancy (see Sections 4.2 ‘Posology and method of administration’ and 4.8 ‘Undesirable effects’)’ has been amended to ‘…the incidence of ovarian hyperstimulation and multiple pregnancy (see Sections 4.2 and 4.8)’.

 

Section 4.8 Undesirable Effects: The listing of adverse events reported is updated presented by body systems. Adverse events added include:

 

Treatment in women

Very rare:

Immune system disorders: Urticaria, oedema, difficulty breathing. Serious cases of allergic reactions including anaphylactic reactions have also been reported.

Respiratory, thoracic and mediastinal disorders: exacerbation or worsening of asthma.

Treatment in men

Common:

Reproductive system and breast disorders: Varicocele

Very common:

General disorders and administration site conditions: Mild to severe injection site reaction (pain, redness, bruising, swelling and/or irritation at the site of injection)

 

The following paragraph has been added ‘Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.’

 

Section 4.9 Overdose: The phrase: ‘….which is further described in ‘Special warnings and special precautions for use’ has been amended to ‘…which is further described in ‘section 4.4’.

 

Section 5.3 Preclinical safety data: The first paragraph has been deleted and replaced with ‘Non-clinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity and genotoxicity additional to that already stated in other sections of the SPC.’

 

Section 6.3 Shelf life: The last sentence ’Do not store above 25°C. Do not freeze.’ has been deleted.

 

Section 6.6 Instructions for use, handling and disposal: The following paragraph has been added:

 

‘Any unused product or waste material should be disposed of in accordance with local requirements.’

 

The sentence ‘The patient should reconstitute the product and inject it immediately.’ has been deleted.

 

Section 9 Date of First Authorisation / Renewal of Authorisation: Date of renewal has been added.

 

Section 10 Date of Revision of the Text: Amended to July 2006.