Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - intrarosa

Document Subject

Generated Narrative: MedicinalProductDefinition mpd6b5caeb3aecc6a916b0a10e40227ee2

identifier: http://ema.europa.eu/identifier/EU/1/17/1255/001

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Intrarosa 6.5 mg pessary

type: Full name

part

part: nan

type: Invented name part

part

part: nan

type: Scientific name part

part

part: nan

type: Strength part

part

part: nan

type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-d6b5caeb3aecc6a916b0a10e40227ee2

identifier: http://ema.europa.eu/identifier/EU/1/17/1255/001

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - intrarosa

Attesters

What is in this leaflet

1. What Intrarosa is and what it is used for
2. What you need to know before you use Intrarosa
3. How to use Intrarosa
4. Possible side effects
5. How to store Intrarosa
6. Contents of the pack and other information

Intrarosa contains the active substance prasterone.

What Intrarosa is used for

Intrarosa is used to treat postmenopausal women having moderate to severe symptoms of vulvar and vaginal atrophy. It is used to relieve menopausal symptoms in the vagina such as dryness or irritation. It is caused by a drop in the levels of oestrogen in your body. This happens naturally after the menopause.

How Intrarosa works

Prasterone corrects the symptoms and signs of vulvar and vaginal atrophy by replacing the oestrogens which are normally produced before menopause by the ovaries of women. It is inserted into your vagina, so the hormone is released where it is needed. This may relieve discomfort in the vagina.

The use of Hormone Replacement Therapy (HRT) carries risks which need to be considered when deciding whether to start taking it, or whether to carry on taking it.

The experience in treating women with a premature menopause (due to ovarian failure or surgery) is limited. If you have a premature menopause the risks of using HRT may be different. Please talk to your doctor.

Before you start (or restart) HRT, your doctor will ask about your own and your family s medical history. Your doctor may decide to perform a physical examination. This may include an examination of your breasts and/or an internal examination, if necessary.

Once you have started using Intrarosa you should see your doctor for regular check-ups (at least every 6 months). At these check-ups, discuss with your doctor the benefits and risks of continuing with Intrarosa.

Go for regular breast screening, as recommended by your doctor.

Do not use Intrarosa if any of the following applies to you. If you are not sure about any of the points below, talk to your doctor before taking Intrarosa,

• If you have or have ever had breast cancer, or if you are suspected of having it;
• If you have cancer which is sensitive to oestrogens, such as cancer of the womb lining (endometrium), or if you are suspected of having it;
• If you have any unexplained vaginal bleeding;
• If you have excessive thickening of the womb lining (endometrial hyperplasia ) that is not being treated;
• If you have or have ever had a blood clot in a vein (thrombosis), such as in the legs (deep venous thrombosis) or the lungs (pulmonary embolism);
• If you have a blood clotting disorder (such as protein C, protein S, or antithrombin deficiency);
• If you have or recently have had a disease caused by blood clots in the arteries, such as a heart attack, stroke or angina;
• If you have or have ever had a liver disease and your liver function tests have not returned to normal;
• If you have a rare blood problem called porphyria which is passed down in families (inherited);
• If you are allergic to prasterone or any of the other ingredients of this medicine (listed in section 6 Contents of the pack and other information ).

If any of the above conditions appears for the first time while taking Intrarosa, stop taking it at once and consult your doctor immediately.

Warnings and precautions

When to take special care with Intrarosa Tell your doctor if you have ever had any of the following problems, before you start the treatment, as these may return or become worse during treatment with Intrarosa. If so, you should see your doctor more often for check-ups:

• fibroids inside your womb;
• growth of womb lining outside your womb (endometriosis) or a history of excessive growth of the womb lining (endometrial hyperplasia);
• increased risk of developing blood clots (see Blood clots in a vein (thrombosis) );
• increased risk of getting a oestrogen-sensitive cancer (such as having a mother, sister or grandmother who has had breast cancer);
• high blood pressure;
• a liver disorder, such as a benign liver tumour;
• diabetes;
• gallstones;
• migraine or (severe) headaches;
• a disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE);
• epilepsy;
• asthma;
• a disease affecting the eardrum and hearing (otosclerosis);
• a very high level of fat in your blood (triglycerides);
• fluid retention due to cardiac or kidney problems.

Stop using Intrarosa and see a doctor immediately
If you notice any of the following conditions when taking HRT:

• any of the conditions mentioned in the Do not use Intrarosa section;
• yellowing of your skin or the whites of your eyes (jaundice). These may be signs of a liver disease;
• if you become pregnant;
• a large rise in your blood pressure (symptoms may be headache, tiredness, dizziness);
• migraine-like headaches which happen for the first time;
• if you notice signs of a blood clot, such as:

• painful swelling and redness of the legs;
• sudden chest pain;
• difficulty in breathing. For more information, see Blood clots in a vein (thrombosis)

Note: Intrarosa is not a contraceptive. If it is less than 12 months since your last menstrual period or you are under 50 years old, you may still need to use additional contraception to prevent pregnancy. Speak to your doctor for advice.

HRT and cancer Intrarosa has not been studied in women with current or history of cancers.
Excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the lining of the womb (endometrial cancer) Taking oestrogen-only HRT tablets for a long time can increase the risk of developing cancer of the womb lining (the endometrium). Intrarosa does not stimulate the endometrium as shown by atrophy of the lining of the womb in all women treated with Intrarosa for one year during the clinical study.

It is uncertain whether a risk exists with Intrarosa used for long term (more than one year) treatments. However, Intrarosa has been shown to have very low absorption into the blood, therefore the addition of a progestagen is not necessary.

If you get bleeding or spotting, it s usually nothing to worry about, but you should make an appointment to see your doctor. It could be a sign that your endometrium has become thicker.

The following risks apply to HRT medicines which circulate in the blood. However Intrarosa is for local treatment in the vagina and the absorption into the blood is very low. It is less likely that the conditions mentioned below will get worse or come back during treatment with Intrarosa, but you should see your doctor if you are concerned.

Breast cancer Evidence suggests that taking combined oestrogen-progestogen and possibly also oestrogen-only HRT increases the risk of breast cancer. The extra risk depends on how long you take HRT. The additional risk becomes clear within a few years. However, it returns to normal within a few years (at most 5) after stopping treatment.

Regularly check your breasts. See your doctor if you notice any changes such as: *
dimpling of the skin; *
changes in the nipple; *
any lumps you can see or feel.

Additionally, you are advised to join mammography screening programs when offered to you.

Ovarian cancer Ovarian cancer is rare - much rarer than breast cancer. The use of oestrogen-only HRT has been associated with a slightly increased risk of ovarian cancer.

The risk of ovarian cancer varies with age. For example, in women aged 50 to 54 who are not taking HRT, about 2 women in 2000 will be diagnosed with ovarian cancer over a 5-year period. For women who have been taking HRT for 5 years, there will be about 3 cases per 2000 users (i.e. about 1 extra case). Cases of ovarian and breast cancer have rarely been reported in women treated with 6.5 mg of prasterone for 52 weeks.

Effect of HRT on heart and circulation Intrarosa has not been studied in women with history of thromboembolic diseases, uncontrolled hypertension or heart disease.

Blood clots in a vein (thrombosis) The risk of blood clots in the veins is about 1.3 to 3-times higher in HRT users than in non-users, especially during the first year of taking it.

Blood clots can be serious, and if one travels to the lungs, it can cause chest pain, breathlessness, fainting or even death.

You are more likely to get a blood clot in your veins as you get older and if any of the following applies to you. Inform your doctor if any of these situations applies to you:

• you are unable to walk for a long time because of major surgery, injury or illness (see also section 3, If you need to have surgery);
• you are seriously overweight (BMI >30 kg/m2);
• you have any blood clotting problem that needs long-term treatment with a medicine used to prevent blood clots;
• if any of your close relatives has ever had a blood clot in the leg, lung or another organ;
• you have systemic lupus erythematosus (SLE);
• you have cancer.

For signs of a blood clot, see Stop using Intrarosa and see a doctor immediately . In clinical studies, no deep vein thrombosis has been observed with intravaginal prasterone while one case of pulmonary embolism which corresponds to an incidence lower with Intrarosa than in the placebo group.

Compare Looking at women in their 50s who are not taking HRT, on average, over a 5-year period, 4 to 7 in 1would be expected to get a blood clot in a vein.

Heart disease (heart attack) / Hypertension For women taking oestrogen-only therapy there is no increased risk of developing a heart disease.

Stroke The risk of getting stroke is about 1.5 times higher in HRT users than in non-users. The number of extra cases of stroke due to use of HRT will increase with age.
No case of stroke has been observed with Intrarosa during clinical studies.

Compare Looking at women in their 50s who are not taking HRT, on average, 8 in 1000 would be expected to have a stroke over a 5-year period. For women in their 50s who are taking HRT, there will be 11 cases in 1000 users, over 5 years (i.e. an extra 3 cases).

Other conditions

• HRT will not prevent memory loss. There is some evidence of a higher risk of memory loss in women who start using HRT after the age of 65. Speak to your doctor for advice;
• You may have vaginal discharge due to melting of the hard fat base which adds to increased vaginal secretions due to treatment. If vaginal discharge occurs, it is not required to stop Intrarosa.
• Intrarosa may weaken condoms, diaphragms and cervical caps made of latex.
• If you have a vaginal infection you will need a course of antibiotics before taking Intrarosa.

Children and adolescents Intrarosa is only used in adult women.

Other medicines and Intrarosa
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

No data on efficacy and safety are available in women currently treated with hormonal therapy such as: androgens, HRT (oestrogen alone or combined with progestogens).

The use of Intraorsa in combination with HRT (oestrogen-only or oestrogen-progestagen combination or androgen treatment) or vaginal oestrogens is not recommended.

Pregnancy, breast feeding and fertility Pregnancy and breast feeding

Intrarosa is for use in postmenopausal women only. If you become pregnant, stop using Intrarosa and contact your doctor.

Fertility

Intrarosa is not meant for women with child-bearing potential. It is not known if this medicine affects fertility.

Driving and using machines Intrarosa does not affect your ability to drive and use machines.

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.
Your doctor will aim to prescribe the lowest dose to treat your symptom for as short as necessary. Speak to your doctor if you think this dose is too strong or not strong enough.

How much to use

Use one pessary once a day, at bedtime.

How to use

Insert the pessary into the vagina with your finger or with an applicator provided in the pack.

Read the instructions on how to use Intrarosa at the end of the leaflet carefully before using this medicine.

How long to use

After initial use, see your doctor at least every 6 months to check if you need to keep using Intrarosa.

If you use more Intrarosa than you should Vaginal douching is recommended.

If you forget to use Intrarosa If you forget to use a pessary, insert one as soon as you remember. However, if the next dose is due in less than 8 hours, skip the missed pessary.

Do not use two pessaries to make up for a forgotten dose.

If you need to have surgery
If you are going to have surgery, tell the surgeon that you are using Intrarosa. You may need to stop using Intrarosa about 4 to 6 weeks before the operation to reduce the risk of a blood clot (see section 2, Blood clots in a vein (thrombosis) ). Ask your doctor when you can start using Intrarosa again.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following diseases are reported more often in women using HRT medicines which circulate in the blood compared to women not using HRT. These risks apply less to vaginally administered oestrogen treatments:

• breast cancer;
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• stroke;
• probable memory loss if HRT is started over the age of 65. For more information about these side effects, see section 2. The side effect the most frequently reported in the clinical studies was vaginal discharge. This is likely due to melting of the hard fat added to an expected increase in vaginal secretions due to treatment. Vaginal discharge does not require to stop Intrarosa.

The following side effects were also reported:

with a common frequency (may affect up to 1 in 10 people): abnormal Pap smear (mostly ASCUS or LGSIL), weight fluctuations (either increase or decrease);

with an uncommon frequency (may affect up to 1 in 100 people): benign cervical or uterine polyps, benign breast mass.

The following side effects have been reported with HRT containing estrogens but not with Intrarosa during clinical studies:

• gall bladder disease
• various skin disorders:

• discoloration of the skin especially of the face or neck known as pregnancy patches
  (chloasma);
• painful reddish skin nodules (erythema nodosum);
• rash with target-shaped reddening or sores (erythema multiforme).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and blisters after EXP. The expiry date refers to the last day of that month.

Store below 30 C.

Do not freeze.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Intrarosa contains

• The active substance is prasterone. Each pessary contains 6.5 mg of prasterone.
• The only other ingredient is the hard fat (adeps solidus).

What Intrarosa looks like and contents of the pack

Intrarosa is a white to off-white, bullet-shaped pessary approximately 28 mm long and 9 mm in diameter at its widest end.

The applicator is made of LDPE and 1% colorant (titanium dioxide).

It is available in blister packs of 28 pessaries with 6 applicators.

Marketing Authorisation Holder

Endoceutics S.A. Rue Belliard 1040 Brussels Belgium

Manufacturer

Basic Pharma Manufacturing B.V. Burgemeester Lemmensstraat 6163 JT Geleen The Netherlands

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgi /Belgique/Belgien, Luxembourg/Luxemburg, Nederland Theramex Belgium BVBA T l/Tel: + 32 (0) 28088INTRAROSA.Enquiries@theramex.com

Deutschland, sterreich Theramex Germany GmbH Tel: + 49 (0) 32 2122 490 INTRAROSA.Enquiries@theramex.com

Espa a Theramex Ireland Limited Tel: + 34 911 143 France Theramex France S.A.S. T l: + 33 (0) 800 100 INTRAROSA.Enquiries@theramex.com

Italia Theramex Italy S.r.l. Tel: + 39 02 81480INTRAROSA.Enquiries@theramex.com

Polska Theramex Poland sp. z o.o. Tel.: + 48 (0) 22 30 77 INTRAROSA.Enquiries@theramex.com

Portugal Tecnimede - Sociedade T cnico-Medicinal, S.A. Tel: + 351 210 414 dmed.fv@tecnimede.pt

United Kingdom (Northern Ireland), Ireland, Malta Theramex UK Limited Tel: + 44 (0) 3330096INTRAROSA.Enquiries@theramex.com

Danmark, sland, Norge, Suomi/Finland, Sverige
Avia Pharma AB Sverige/Sv j /Ruosti Tlf/S mi/Tlf/Puh/Tel: + 46 (0) 8 544 900 , esk republika, Eesti, , Hrvatska, , Latvija, Lietuva, Magyarorsz g, Rom nia, Slovenija, Slovensk republika Theramex Ireland Limited Tel/Te ./ : + 353 (0) 15138INTRAROSA.Enquiries@theramex.com

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

Instructions on how to use Intrarosa How should I use Intrarosa

• Insert one prasterone pessary in your vagina once a day at bedtime with an applicator or your finger. Before you start
• Empty your bladder and wash your hands before handling the pessary and applicator.
• Tear off one wrapped pessary from the 7-pessary strip. A. Using the applicator

STEP 1 1A. Remove 1 applicator from the package. 1B. Pull back on the plunger until it stops to activate the applicator. The applicator must be activated before use. Place the applicator on a clean surface.

STEP 5 Select the position for insertion of the pessary that is most comfortable for you. 5a. Lying position

STEP 2 Slowly pull the plastic tabs on the pessary away from each other while keeping the pessary still between your fingers. Carefully remove the pessary from the plastic wrap.
If a pessary falls on an unsanitary surface, replace it with a new one.

5b. Standing position

STEP 3 Place the flat end of the pessary into the open end of the activated applicator as shown. You are now ready to insert the pessary into your vagina.

STEP 6 Gently slide the pessary end of the applicator into your vagina as far as it will comfortably go.

Do not use force.

STEP 4 Hold the applicator between your thumb and middle finger.
Leave your index (pointer) finger free to press the applicator plunger after the applicator is inserted into your vagina.

STEP 7 Press the applicator plunger with your index (pointer) finger to release the pessary. Remove the applicator. Wash it or throw it away after using for one week (two extra applicators are provided). To wash the applicator: Take it to pieces; Rinse the 2 pieces for 30 seconds under running water; Wipe with a paper towel and reassemble. Keep it in a clean place. B. Using the finger Follow the above instructions of Step 2, and then insert the pessary into the vagina with your finger as far as it can comfortably go. Do not use force.

ANNEX IV SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION(S) Scientific conclusions Taking into account the PRAC Assessment Report for the non-interventional imposed PASS final study report for the medicinal product(s) mentioned above, the scientific conclusions of the CHMP are as follows: Intrarosa (prasterone) is removed from the additional monitoring list as the condition to the marketing authorisation has been fulfilled. This relates to the non-interventional PASS - Drug Utilisation Study (DUS) to describe the baseline characteristics, utilisation patterns of EU postmenopausal women initiating treatment with Intrarosa and to assess whether EU prescribers abide by the contraindications stated in the EU SmPC. Therefore, the statement that this medicinal product is subject to additional monitoring and that this will allow quick identification of new safety information, preceded by an inverted equilateral black triangle, is removed from the summary of product characteristics and the package leaflet. In addition, the MAH took the opportunity to introduce a change to the list of local representatives. The CHMP agrees with the scientific conclusions made by the PRAC. Grounds for the variation to the terms of the marketing authorisation(s) On the basis of the scientific conclusions for the results of the study for the medicinal product(s) mentioned above, the CHMP is of the opinion that the benefit-risk balance of these medicinal product(s) is unchanged, subject to the proposed changes to the product information. The CHMP is of the opinion that the terms of the marketing authorisation of the medicinal product mentioned above should be varied.