Reasons for adding or updating:

• Change to section 1 - Name of the medicinal product
• Change to section 2 - Qualitative and quantitative composition
• Change to section 4.2 - Posology and method of administration
• Change to section 4.3 - Contraindications
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
• Change to section 4.6 - Fertility, pregnancy and lactation
• Change to section 4.8 - Undesirable effects
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 6.6 - Special precautions for disposal and other handling
• Change to section 9 - Date of first authorisation/renewal of the authorisation
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 01-Mar-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

There are a number of administrative changes throughout the SPC due to the QRD version 9 recommendations.

Reasons for adding or updating:

• Change to section 4.3 - Contraindications
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.8 - Undesirable effects

Date of revision of text on the SPC: 18-Nov-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



4.3 Contra-indications

1. Known hypersensitivity to progesterone or any of the excipients

2. Undiagnosed vaginal bleeding

3. Known or suspected progesterone-sensitive malignant tumours

4.

 

Porphyria

 

5. Thrombophlebitis, thromboembolic disorder, cerebral apoplexy, or

patients with an history of these conditions

4.

 

6.Missed abortion

 

4.4 Special warnings and special precautions for use

The pre-treatment physical examination should include special reference to

breast and pelvic organs, as well as Papanicolaou smear.

Cautious use in severe hepatic insufficiency.

In cases of breakthrough bleeding, as in all cases of irregular vaginal bleeding,

non-functional causes should be considered. In cases of undiagnosed vaginal

bleeding, adequate diagnostic measures should be undertaken.

Crinone is not indicated in threatened abortion. Treatment should be

discontinued in the event of a missed abortion.

The physician should be alert to the early manifestations of thrombotic

disorders (thrombophlebitis, cerebrovascular disorder, pulmonary embolism

and retinal thrombosis). Should any of these symptoms occur or be suspected,

the drug should be discontinued immediately. Patients who have risk factors

for thrombotic disorders should be kept under careful observation.

Although risk of thromboembolism has been associated with estrogens, a link

with progestins remains questionable. Therefore, in women with generally

recognised risk factors for thrombo-embolic events, such as personal or family

history, treatment with Crinone may further increase the risk. In these women,

the benefits of Crinone administration need to be weighed against the risks. It

 

should be noted however, that pregnancy itself carries an increased risk of

thrombo-embolic events.

Because progestogens may cause some degree of fluid retention, conditions

that might be influenced by this factor (e.g, epilepsy, migraine, asthma,

cardiac or renal dysfunction) require careful observation.

Patients who have a history of depression should be carefully observed and

the drug discontinued if the depression recurs to a serious degree.

A decrease in glucose tolerance as been observed in a small number of

patients on oestrogen-progestin combination drugs. The mechanism of this

decrease is not known. For this reason, diabetic patients should be carefully

observed while receiving progestin therapy.

Avoid concurrent use with other intravaginal preparations. See section 4.5.

The excipient sorbic acid m

ay cause local skin reactions (e.g. contact dermatitis) or

 

vaginal irritation.

 

4.8 Undesirable effects

The adverse reactions reported below are classified according to frequency of

occurrence as follows:

 

Very common (

 

! 1/10)

 

Common (

 

! 1/100 to < 1/10)

 

Uncommon (

 

! 1/1,000 to < 1/100)

 

Rare (

 

! 1/10,000 to < 1/1,000)

 

Very rare (< 1/10,000)

Crinone is generally well-tolerated. In clinical studies, the following adverse

events have been reported during Crinone therapy. Most adverse events

observed in clinical studies cannot be distinguished from the symptoms

common in early pregnancy.

Common

(>1/100 – 1/10)

 

Headache, Somnolence,

abdominal pain, Breast Tenderness, Vaginal

 

irritation,

 

Itching or Burning.

 

Post Marketing Reports

In addition, intermenstrual bleeding (spotting),

vaginal irritation,

 

hypersensitivity reactions usually manifesting as skin rash, and other mild

application site reactions have been reported post-marketing.

Rare events of urticaria and pruritis were noted.

For adverse reactions identified during post-marketing surveillance,

quantification of frequency has not been attempted, but it is most likely

uncommon to very rare.

Reasons for adding or updating:

• Change to section 7 - Marketing authorisation holder
• Change to section 8 - Marketing authorisation number(s)
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 01-Mar-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

MA holder changed to Merck Serono Limited, with new product licence number.

Reasons for adding or updating:

• Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC: 04-Jan-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.8: Addition of

"hypersensitivity reactions usually manifesting as skin rash,"

Reasons for adding or updating:

• Correction of spelling/typing errors

Date of revision of text on the SPC: 19-May-2010

Legal Category:POM

Black Triangle (CHM): NO

Reasons for adding or updating:

• Change to section 4.2 - Posology and method of administration
• Change to section 4.3 - Contraindications
• Change to section 4.4 - Special warnings and precautions for Use
• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
• Change to section 4.8 - Undesirable Effects
• Change to section 6. 6 - Instructions for use, handling and disposal

Date of revision of text on the SPC: 19-May-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

The following sections have been updated:

4.2              Posology and method of administration

Method of Administration

 

Crinone is applied directly from the specially designed sealed applicator into the vagina. The applicator should be removed from the sealed wrapper. The twist-off cap should not be removed at this time.

 

1.      The applicator should be gripped firmly by the thick end. It should be shaken down like a thermometer to ensure that the contents are at the thin end.

2.      The tab should be twisted off and discarded.

3.      The applicator may be inserted while patient is in a sitting position or when lying on her back with the knees bent. The thin end of applicator should be gently inserted well into the vagina.

4.      The thick end of the applicator should be pressed firmly to deposit gel. The applicator should be removed and discarded in a waste container.

4.3       Contra-indications

 

1.      Known hypersensitivity to progesterone or any of the excipients

2.      Undiagnosed vaginal bleeding

3.      Known or suspected progesterone-sensitive malignant tumours

4.      Porphyria

4.4       Special warnings and special precautions for use

 

            Cautious use in severe hepatic insufficiency.

 

In cases of breakthrough bleeding, as in all cases of irregular vaginal bleeding, non-functional causes should be considered. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures should be undertaken.

 

Crinone is not indicated in threatened abortion. Treatment should be discontinued in the event of a missed abortion.

 

Although risk of thromboembolism has been associated with estrogens, a link with progestins remains questionable. Therefore, in women with generally recognised risk factors for thrombo-embolic events, such as personal or family history, treatment with Crinone may further increase the risk. In these women, the benefits of Crinone administration need to be weighed against the risks. It should be noted however, that pregnancy itself carries an increased risk of thrombo-embolic events.

 

Avoid concurrent use with other intravaginal preparations. See section 4.5.

 

The excipient sorbic acid may cause local skin reactions (e.g. contact dermatitis) or vaginal irritation.

4.5       Interaction with medicaments and other forms of interactions

 

Crinone is not recommended for use concurrently with other vaginal preparations.

 

Although there is evidence of interaction between oral progestogens and CYP3A4 inducers, resulting in a decrease of serum progestogen levels, no significant consequences on progesterone levels is expected from concurrent administration of CRINONE^® vaginal gel with CYP3A inducers

4.8       Undesirable effects

 

            Common (>1/100 – 1/10)

 

Headache, Somnolence, Breast Tenderness, Vaginal irritation, Itching or Burning

 

Post Marketing Reports

In addition, intermenstrual bleeding (spotting) and other mild application site reactions have been reported post-marketing.

Rare events of urticaria and pruritis were noted.

6.6       Instructions for use/handling

 

            No special requirements

Reasons for adding or updating:

• Change to section 6. 4 - Special Precautions for Storage
• Change to section 7 - Marketing Authorisation Holder
• Change to section 9 - Date of Renewal of Authorisation
• Change to section 10 (date of (partial) revision of the text

Date of revision of text on the SPC: 01-Jun-2004

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 6.4 Special precautions for storage: A typo has been corrected.

 

Section 7 Marketing Authorisation Holder: ‘Serono Pharmaceuticals Ltd’ has been changed to ‘Serono Ltd’.

 

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 June 2004.

Reasons for adding or updating:

• No reasons supplied

Reasons for adding or updating:

• No reasons supplied