Tog©gyne*

400 micrograms tablets Misoprostol

PACKAGE LEAFLET:    ^K

INFORMATION FOR THE USER

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

-    Keep this leaflet. You may need to read it again.

-    If you have any further questions, ask your doctor.

-    This medicine has been prescribed for you only.

Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-    If you get any side effects talk to your doctor. This includes any possible side effects not listed in this leaflet.

What is in this leaflet:

1.    What Topogyne is and what it is used for

2.    What you need to know before you take Topogyne

3.    How to take Topogyne

4.    Possible side effects

5.    How to store Topogyne

6.    Contents of the pack and other information

1.    What Topogyne is and what it is used for

Topogyne tablets contain misoprostol, which is similar to a chemical substance called ‘prostaglandin’ that your body produces naturally. Misoprostol triggers contractions of the womb and softens the cervix.

Topogyne is used after taking another medicine called mifepristone for termination of pregnancy. It should be taken no later than 49 days after the first day of your last menstrual period.

2.    What you need to know before you take Topogyne Do not take Topogyne

-    if you are allergic to misoprostol, any other prostaglandin or any of the other ingredients of this medicine (listed in section 6)

-    if the pregnancy has not been confirmed by ultrasound scan or biological tests

-    if the first day of your last period was more than 49 days (7 weeks) ago

-    if your doctor suspects an ectopic pregnancy (the egg is implanted outside the womb)

-    if you cannot take mifepristone (mifepristone is used in combination with Topogyne)

Warnings and precautions

Talk to your doctor before taking Topogyne

-    if you have liver or kidney disease

-    if you suffer from anaemia or malnutrition

-    if you have cardiovascular disease (heart or circulatory disease)

-    if you are at increased risk of cardiovascular disease. Risk factors include being aged over 35 years and a cigarette smoker or having high blood pressure, high blood cholesterol levels or diabetes

-    if you have an illness that affects the clotting of your blood

-    if you have had a previous caesarean section or surgery of the womb

If you use a contraceptive coil, it must be removed before you take the first medicine, mifepristone.

Before taking mifepristone and Topogyne your blood will be tested for Rhesus factor. If you are Rhesus negative your doctor will advise you of the routine treatment required.

Other medicines and Topogyne

Tell your doctor if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

In particular tell your doctor if you are taking any of the following:

-    Non-steroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic acid or diclofenac

-    Antacid medicines or an antacid medicine containing magnesium (used to treat heartburn and acid indigestion)

Pregnancy, breast-feeding and fertility

Pregnancy

Failure of pregnancy termination (continuing pregnancy) after taking Topogyne after the first medicine (mifepristone) has been associated with birth defects. Defects in newborns have also been seen when this medicine is taken on its own. You must take the other medicine, mifepristone, 36 - 48 hours before taking Topogyne.

The risk of failure of this medicine increases

-    If it is taken later than 49 days after the first day of your last menstrual period

-    If it is not taken orally

-    With the duration of the pregnancy

-    With the number of pregnancies you have had before

If termination of the pregnancy fails after taking this medicine there is an unknown risk to the foetus. If you decide to continue with the pregnancy, careful pre-natal monitoring and repeated ultrasound examinations, with a special attention to the limbs, in a specialised clinic must be carried out. Your doctor will advise further.

If you decide to continue with the termination of the pregnancy a new procedure will be used. Your doctor will advise you of the options.

You should avoid getting pregnant again before your next period after taking this medicine. You should start contraception immediately after the termination of the pregnancy is confirmed by the doctor.

Breastfeeding

If you are breast-feeding, talk to your doctor before using this medicine. Do not breastfeed while taking mifepristone and misoprostol as these medicines are passed into breast milk.

Fertility

This medicine does not affect fertility. You can become pregnant again as soon as your termination is completed. You should start contraception immediately after the termination of the pregnancy is confirmed.

Driving and using machines

This medicine can cause dizziness. Take special care when driving or using machines after taking this medicine until you know how Topogyne affects you.

3. How to take Topogyne

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Dosage in Adults

•    One tablet to be taken orally.

Taking the Tablet

•    Swallow the tablet whole with a glass of water,

•    36 to 48 hours after taking 600 mg of mifepristone

•    You need to rest for at least 3 hours after taking this tablet.

•    If you vomit within 30 minutes of taking the tablet, talk to your doctor immediately. You will need to take another tablet.

Important things to remember when taking this medicine:

This tablet must be taken orally Topogyne must be taken 36 - 48 hours after taking 600 mg of mifepristone

If you do not follow these instructions the risks associated with this medicine will increase

The schedule for taking Topogyne will be as follows.

1.    At the prescribing centre you will be given the first drug mifepristone, which must be taken orally.

2.    36 - 48 hours after this, you will take Topogyne orally. You must

rest for at least 3 hours after taking this medicine.

3.    The embryo may be expelled within a few hours of taking Topogyne or during the next few days. You will have vaginal bleeding which will last for an average of 12 days after taking the first drug, mifepristone, and the flow will become lighter as time continues.

4.    You must return to the centre within 14 - 21 days of taking the first medicine, mifepristone, for a check-up consultation to make sure the expulsion is complete.

Contact your prescribing centre immediately:

-    if you have vaginal bleeding for longer than

12 days and/or if it is very heavy (e.g. you need more than 2 sanitary pads per hour for 2 hours)

-    if you have severe abdominal pain

-    if you have a fever or if you are feeling cold and shivering.

Other important points to remember:

•    Vaginal bleeding does not mean the expulsion has been completed.

•    Do not take this medicine if the blister foil is damaged or if the tablet has been stored outside the packaging.

•    The risk of side effects increases if you take this medicine later than 49 days after the first day of your last menstrual period or if you do not take it orally.

If pregnancy continues or expulsion is incomplete, your doctor will advise you of the options for termination of the pregnancy.

It is recommended that you do not travel too far away from the prescribing centre until the check-up consultation is done.

In case of emergency or if you have any questions, telephone or visit your prescribing centre. You do not have to wait for your check-up appointment.

Use in children

Only limited data is available on the use of misoprostol in adolescents.

If you take more Topogyne than you should

If you take too many tablets, contact your doctor immediately or go to the nearest hospital casualty department.

The doctor will give you the exact amount of Topogyne; it is therefore unlikely that you will take too many tablets. Taking too many tablets may cause symptoms such as drowsiness, shaking, fits, difficulty in breathing, abdominal pain, diarrhoea, fever, chest pain, low blood pressure and a slow heartbeat that can be fatal.

If you forget to take Topogyne

If you forget to take mifepristone or Topogyne it is likely that the termination will not be fully effective. Talk to your doctor or the prescribing centre if you forget to take Topogyne.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4.    Possible side effects

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

If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet.

The following side effects may occur:

Serious Side Effects

The risk of serious side effects increases if you take this medicine later than 49 days after the first day of your last menstrual period or if you do not take it orally.

Serious side effects include:

•    allergic reaction. Severe skin rashes such as itchy red spots, blisters or lesions.

Other serious side effects include:

•    cardiovascular accidents. Chest pain, difficulty breathing, confusion, or an irregular heartbeat.

•    cases of serious or fatal toxic or septic shock. Fever with aching muscles, rapid heart rate, dizziness, diarrhoea, vomiting or feeling weak.

These side effects may occur if this medicine is taken later than 49 days after the first day of your last menstrual period or if you do not take it orally.

If you experience any of these side effects contact your doctor IMMEDIATELY or go to your nearest hospital casualty department.

Other side effects

Very common (may affect more than 1 in 10 people):

•    uterine contractions or cramping

•    diarrhoea

•    feeling sick (nausea) or being sick (vomiting)

Common (may affect up to 1 in 10 people):

•    heavy vaginal bleeding

•    abdominal pain

•    gastro-intestinal cramping light or moderate

•    infection of the uterus (endometritis and pelvic inflammatory disease)

•    Rare (may affect up to 1 in 1,000 people):

•    fever

•    foetal death

•    birth defects

•    headache, dizziness and generally feeling unwell or tired

•    hives and skin disorders which can be serious Very rare (may affect up to 1 in 10,000 people)

•    Localised swelling of face and/or larynx which can be with urticaria

Other side effects include

•    feeling cold, shivering

•    Back pain

Tell your doctor if any of the side effects get serious or if you notice any other unwanted or unexpected effects.

5.    How to store Topogyne

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 after “Exp.”. The expiry date refers to the last day of that month.

Store below 25°C.

Do not use if the box or the blister packs show signs of damage. Do not use if the tablet has been stored outside the blister pack. Do not throw away any medicines via wastewater.

Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information What Topogyne contains

The active substance is misoprostol.

One tablet of Topogyne contains 400 microgram misoprostol.

The other ingredients are microcrystalline cellulose, hypromellose, sodium starch glycolate (type A), hydrogenated castor oil.

What Topogyne looks like and contents of the pack

White, round, flat tablet with a diameter of 11 mm and thickness of 4.4 mm, with “M400” engraved on one side.

Topogyne is available in pack sizes of 1, 4, 16 or 40 tablets in perforated unit dose PVC-PCTFE/Alu or Alu/Alu blisters.

Marketing Authorisation Holder and Manufacturer

Marketing authorisation holder

Exelgyn

216 Boulevard Saint Germain

75007 Paris

France

Manufacturer Nordic Pharma BV Tolweg 15 3741 LM Baarn The Netherlands

This medicinal product is authorised in the Member States of the EEA under the following names:

Austria: Topogyne Belgium: Topogyne Bulgaria: Topogyne Croatia: Mispregnol Czech Republic: Mispregnol Germany: MisoOne Denmark: MisoOne Estonia: Topogyne Spain: MisoOne Finland: Misoone France: MisoOne Greece: MisoOne Italy: Misoone Luxembourg: Topogyne Latvia: Misoone The Netherlands: MisoOne Norway: Misoone Portugal: Topogyne Romania: Topogyne Sweden: Topogyne Slovenia: Topogyne Slovakia: Mispregnol UK: Topogyne

This leaflet was last approved in 03/2016

Jog©gyne*    iblet

Material for Patients    Misoprosto!

Information on Medical Termination of Pregnancy

You have chosen the medical termination of pregnancy [ToP] method (also called the medical abortion method). This leaflet will provide you with some information that you should be aware of before taking the medicine including the steps involved in your treatment and what to do if you experience any problems. It is important that you read and consider this information carefully. Before taking this medicine for the ToP:

-    Please read the mifepristone and misoprostol patient leaflets (PIL)

-    Inform your doctor about the following:

•    if you have liver or kidney disease

•    if you suffer from anaemia or malnutrition

•    if you have cardiovascular disease (heart or circulatory disease)

•    if you are at increased risk of cardiovascular disease. Risk factors include being aged over 35 years and a cigarette smoker or having high blood pressure, high blood cholesterol levels or diabetes

•    if you have an illness that affects the clotting of your blood

•    if you have had a previous caesarean section or surgery of the womb

If you feel uncomfortable or are worried about the ToP or if you have further questions, don’t hesitate to contact your doctor. A safety card is available for you below. Your doctor should have noted all relevant contact details and where to go should you experience any problems or require more advice.

This ToP is carried out in 3 steps:

1.    At this stage, you have taken the 600 mg oral dose Mifegyne®

(3 tablets) 36 to 48h ago.

2.    You are now about to have the 400 mcg oral dose Topogyne®: one tablet to be taken.

3.    2 to 3 weeks after the first drug (Mifegyne®) is taken, a follow-up visit is required (this is compulsory). This visit is important because your doctor will verify that the abortion is successful and make sure that everything is all right.

What will you experience during the ToP:

- Medical ToP induces womb contractions. You may experience pain, feel tired, have nausea, vomiting and diarrhoea, so it is best you try to remain comfortable and to have somebody with you. If you have any pain do take the painkillers that your doctor prescribed to you.

-    The ToP will occur with vaginal bleeding that can be heavier than your menstrual bleeding, contains blood clots and a gelatinous white ball is sometimes visible. Bleeding can happen very quickly after taking Topogyne^® but it may also happen hours later.

•    The embryo may be expelled within a few hours after taking Topogyne® or during the next few days.

•    Bleeding lasts for an average of 12 days after you take Mifegyne^®. You must return to your medical centre within 14-21 days for a check up as bleeding is not in any way a proof of complete expulsion.

-    After a ToP, fertility resumes immediately. You must speak with your doctor about the best contraceptive method for you and start using contraception the same day as the termination of pregnancy is confirmed.

Contact your doctor immediately in case:

-    You vomit within 30 minutes of taking Topogyne^®. Your physician will determine whether another dose of Topogyne^® is necessary.

-    You have abnormal bleeding in terms of duration and amount of blood (seek medical advice if you bleed for more than 12 days and/or need more than 2 sanitary pads per hour for 2 hours).

-    You have severe abdominal pain that persists despite taking painkillers.

-    You have a fever or if you are feeling cold and shivering.

During the follow-up visit your doctor will check if the expulsion is complete. If the ToP fails and you decide to carry on with the pregnancy, you should be aware that there is a risk of birth defects in newborns associated with misoprostol use. You should take this into consideration when making a decision to carry your pregnancy to term or not:

-    If you decide to continue with the termination of your pregnancy a new procedure will be used. Your doctor will advise you of the options.

-    In case you choose to carry your pregnancy to term, make sure you have a special follow-up with careful pre-natal monitoring and repeated ultrasound examinations in a specialised clinic.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in the Patient Information Leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard By reporting side effects you can help provide more information on the safety of this medicine.

IF AT ANY TIME you are worried or if the following occurs :

-    fever lasting longer than 24 hours

-    pain that persists despite taking painkillers

-    significant and persistent blood loss (use of more than 2 sanitary pads per hour for 2 hours)

-    faintness, or any question

Please contact your doctor or go to the prescribing centre :

®_

For the follow-up visit please come to the office on :_/_/_ at_h

Jog© gyne*    ablet

Misoprostol

Material for Healthcare Professionals

How to manage the risk to your patients in Medical Termination of Pregnancy (MToP)

Please consult the mifepristone and misoprostol SmPC/prescribing information before performing a MToP.

As a reminder, the approved protocol up to 49 days of amenorrhea is the following:

-    Mifepristone: 600 mcg oral dose

-    Misoprostol: 400 mcg oral dose (i.e. 1 tablet of Topogyne®)

36 to 48 h after mifepristone intake

Unlike other misoprostol tablets, each Topogyne® tablet contains 400 mcg misoprostol, so one Topogyne® tablet only must be given. The management of the risk to the patient consists of two steps:

1.    Counselling

2.    Verification of complete expulsion during the follow-up visit which must take place within a period of 14 to 21 days after administration of the mifepristone

To minimize the risk associated with Topogyne®, you are advised to counsel your patient regarding the following.

INFORMATION TO BE TAKEN INTO ACCOUNT DURING THE

COUNSELLING

Patient medical history

MToP method is suitable for most patients. However, due to the prostaglandin intake, you have to consider the following pre-existing conditions before the start of the procedure:

-    scarred uterus,

-    cardiovascular risks (e.g. being aged over 35 years with chronic smoking, hyperlipidemia, diabetes),

-    established cardiovascular disease

-    Rhesus negative

What to do:

-    Discuss the medical history with the patient

-    Treat the patient with caution when they have the pre-existing conditions

Fertility

This method has no influence on the fertility of the patient.

What to do:

-    Discuss the choice of the contraception method with the patient preferably during the counselling visit in order to prescribe the most suitable method to her and provide advice on when to start the contraception following the medical ToP.

Bleeding

Vaginal bleeding is a normal part of the abortion procedure and the

patient should be made aware of this.

What to do:

Instruct the patient on the following:

-    Occurrence and intensity of prolonged vaginal bleeding:

•    Bleeding can start very quickly after misoprostol intake

•    Expulsion can occur within 4 hours, or during the next few days

•    Duration of bleeding can last up to 12 days

-    To contact physician immediately in case of abnormal bleeding:

•    If more than 12 days and/or

•    If more than 2 sanitary pads per hour for 2 hours are needed

-    Bleeding is not in any way proof of complete expulsion therefore a follow-up visit is required to confirm termination of the pregnancy

-    If persistent bleeding occurs after the follow-up visit patient needs to contact the doctor

-    Persistence of vaginal bleeding could signify incomplete abortion and appropriate treatment should be considered.

Note down on safety card:

-    Phone number and address of the prescribing centre so patient can contact you or another physician should they need to

-    Date of follow-up visit for the patient Infections

Toxic or septic shocks following infections are very rare. However some serious or fatal cases have been reported following MToP performed with misoprostol given other than oral (i.e. vaginally). No cases have been reported so far when misoprostol was taken by the approved oral route.

These infections are the consequence of atypical pathogens.

What to do:

Instruct the patient on the following:

-    Contact physician immediately in case of

•    Fever

•    Pain despite intake of painkillers

VERIFICATION OF COMPLETE EXPULSION

The medical ToP procedure consists in 3 steps:

•    Mifegyne^® intake,

•    Topogyne^® intake,

•    and the follow-up visit.

If the medical abortion is done with the regimen mentioned in the Topogyne® SmPC, the risk of ongoing pregnancy is below 1%. This risk increases when other regimens are used. In case of ongoing pregnancy, it is essential for the patient to be informed about the potential risks due to Mifegyne^®/Topogyne^® to decide to carry the pregnancy to term or not.

What to do:

During follow-up visit verify complete expulsion

In case the medical ToP method failed, inform the patient about her

choices:

-    Terminate the pregnancy. In this case a second different method for ToP should be used

-    Carry the pregnancy to term.

In case the patient decides to carry the pregnancy to term:

-    It is important to inform the patient about the risk of malformations of the newborn due to the exposure to drug(s)

-    Provide information on special follow up appointments with ultrasound scan monitoring in a specialized centre.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. Please also inform Exelgyn Pharmacovigilance department (pv@nordicpharma.com).