Rapilysin

Основна информация

  • Търговско наименование:
  • Rapilysin
  • Използвай за:
  • Хората
  • Вид на лекарството:
  • алопатични наркотици

Документи

Локализация

  • Предлага се в:
  • Rapilysin
    Европейски съюз
  • Език:
  • английски

Терапевтична информация

  • Терапевтична група:
  • B01 Antithrombotic agents
  • Терапевтична област:
  • Myocardial Infarction
  • Терапевтични показания:
  • Rapilysin is indicated for the thrombolytic treatment of suspected myocardial infarction with persistent ST elevation or recent left bundle branch block within 12 hours after the onset of acute-myocardial-infarction symptoms.,
  • Каталог на резюме:
  • Revision: 25

Състояние

  • Източник:
  • EMA - European Medicines Agency
  • Статус Оторизация:
  • Authorised
  • Номер на разрешението:
  • EMEA/H/C/000105
  • Дата Оторизация:
  • 28-08-1996
  • EMEA код:
  • EMEA/H/C/000105
  • Последна актуализация:
  • 27-03-2019

Доклад обществена оценка

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© European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged.

EMA/55700/2016

EMEA/H/C/000105

EPAR summary for the public

Rapilysin

reteplase

This is a summary of the European public assessment report (EPAR) for Rapilysin. It explains how the

Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in

favour of granting a marketing authorisation and its recommendations on the conditions of use for

Rapilysin.

What is Rapilysin?

Rapilysin is a powder and solvent that are made up into a solution for injection. It contains the active

substance reteplase.

What is Rapilysin used for?

Rapilysin is used within 12 hours of a suspected heart attack to help dissolve the blood clots

obstructing the flow of blood to the heart muscle.

The medicine can only be obtained with a prescription.

How is Rapilysin used?

Rapilysin should be prescribed by doctors who have experience in using medicines that dissolve blood

clots and who can monitor its use.

Treatment with Rapilysin should be started as soon as possible after the start of heart attack

symptoms. Rapilysin is given as two injections, 30 minutes apart. Each injection is given into a vein

slowly, but in less than two minutes. Other medicines that prevent clotting (aspirin and heparin)

should be given before and after the Rapilysin injection to stop clots from forming again. However,

Rapilysin and heparin or aspirin must not be given in the same syringe.

Rapilysin

EMA/55700/2016

Page 2/2

How does Rapilysin work?

The active substance in Rapilysin, reteplase, is a copy of a natural enzyme called t-PA that has been

modified so that it starts working faster and for longer. Reteplase activates the production of an

enzyme called plasmin, which breaks up blood clots. Following a heart attack, Rapilysin can help

dissolve blood clots that have formed in the arteries supplying the heart muscle, thereby restoring

normal blood flow to the heart.

How has Rapilysin been studied?

Rapilysin has been studied in more than 21,000 patients in four studies. Rapilysin has been compared

with other medicines used to dissolve blood clots: streptokinase in 6,000 patients and alteplase in

about 15,000 patients. The studies looked at the number of patients who had died 30 to 35 days after

treatment, and at the number of patients who had heart failure (an inability of the heart to pump

enough blood around the body) or a stroke.

What benefit has Rapilysin shown during the studies?

Rapilysin was more effective than streptokinase in reducing the number of patients with heart failure,

and it was as effective as streptokinase in preventing death. Rapilysin was also as effective as

alteplase in preventing death and stroke.

What is the risk associated with Rapilysin?

The most common side effects with Rapilysin (seen in more than 1 patient in 10) are bleeding at the

injection site, recurrent ischaemia (reduced blood supply to parts of the body) or angina (severe chest

pain), hypotension (low blood pressure), heart failure or pulmonary oedema (build-up of fluid on the

lungs), and reactions at the site of the injection, such as burning sensations. For the full list of all side

effects reported with Rapilysin, see the package leaflet.

Rapilysin must also not be used in patients who are at risk of bleeding because of other diseases,

treatment with other medicines, high blood pressure, previous bleeding or recent surgery. For the full

list of restrictions, see the package leaflet.

Why has Rapilysin been approved?

The CHMP decided that Rapilysin’s benefits are greater than its risks for and recommended that it be

given marketing authorisation.

Other information about Rapilysin

The European Commission granted a marketing authorisation valid throughout the European Union for

Rapilysin on 9 November 1996.

The full EPAR for Rapilysin can be found on the Agency’s website: ema.europa.eu/Find

medicine/Human medicines/European public assessment reports. For more information about

treatment with Rapilysin, read the package leaflet (also part of the EPAR) or contact your doctor or

pharmacist.

This summary was last updated in 02-2016.

Листовка за пациента: състав, показания, Нежелани лекарствени реакции, дозиране, взаимодействия, бременност, кърмене

B. PACKAGE LEAFLET

Package leaflet: Information for the user

Rapilysin 10 U powder and solvent for solution for injection

reteplase

Read all of this leaflet carefully before you start using 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 or your pharmacist.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

What Rapilysin is and what it is used for

What you need to know before Rapilysin is given to you

How to use Rapilysin

Possible side effects

How to store Rapilysin

Contents of the pack and other information

1.

What Rapilysin is and what it is used for

Rapilysin contains the active substance reteplase(a recombinant plasminogen activator). It is a

thrombolytic medicine used to dissolve blood clots that have formed in certain blood vessels and to

restore the blood flow in these blocked vessels (=thrombolysis).

Rapilysin is used after an acute myocardial infarction (heart attack) in order to dissolve the blood clot

causing the heart attack. It is given within 12 hours after the onset of symptoms.

2.

What you need to know before Rapilysin is given to you

The doctor will ask you questions before giving you Rapilysin, to find out if you have an increased

risk of bleeding.

Do not use Rapilysin

if you are allergic to reteplase or any of the other ingredients of this medicine (listed in section

if you have a bleeding disorder.

if you are taking medicine to thin your blood (oral anticoagulants, e.g. warfarin).

if you have a brain tumour or a malformed blood vessel or a vessel wall dilatation (aneurysm) in

the brain.

if you have other tumours associated with an increased risk of bleeding.

if you have had a stroke.

if you have had external heart massage within the past 10 days.

if you have severe uncontrolled high blood pressure (hypertension).

if you have an ulcer in the stomach or small intestine.

if you have enlarged blood vessels in the gullet (oesophagus) (frequently caused by liver

disease).

if you have severe liver or kidney disease.

if you have acute inflammation of the pancreas or pericardium (the sac surrounding the heart),

or an infection of the heart muscle (bacterial endocarditis).

if you have in the past 3 months had severe bleeding, a major injury or major surgery (e.g.

coronary artery bypass graft, or surgery or injury to the head or spine), given birth, or had an

organ biopsy or other medical / surgical procedure.

Warnings and precautions

Bleeding

The most common side effect of Rapilysin is bleeding. Therefore Rapilysin must be given only in the

presence and under the instructions of an emergency doctor.

Pay careful attention to all possible bleeding sites (e.g. injection sites). Heparin, which is given

together with Rapilysin, may also increase bleeding.

The risks of Rapilysin treatment may be increased if you have any of the following conditions:

diseases of the blood vessels in the brain

systolic blood pressure higher than 160 mmHg

bleeding in the gastrointestinal, urinary or genital tract within the past 10 days

high likelihood of a blood clot in the heart (e.g. as a result of narrowing of a heart valve or atrial

fibrillation)

septic inflammation of a vein with blood clotting (septic thrombophlebitis) or blocked blood

vessels at an infected site

age over 75 years

any other condition in which bleeding might be especially dangerous or might occur at a site

where it would be difficult to control

At present, little data are available on the use of Rapilysin in patients with diastolic blood pressure

higher than 100 mmHg.

Abnormal heart beats (arrhythmias)

Thrombolytic treatment may cause the heart to beat irregularly. Therefore tell the medical staff

immediately if you

feel palpitations or an irregular heart beat

Repeated use

At present there is no experience with repeated use of Rapilysin. Therefore, repeated use is not

recommended. Antibody formation to the reteplase molecule has not been seen.

Children

Safety and effectiveness of Rapilysin in children have not been established. Treatment of children with

Rapilysin is not recommended.

Other medicines and Rapilysin:

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other

medicines.

Heparin and other medicines that thin the blood (anticoagulants) and acetylsalicylic acid (a substance

used in many medicines used to relieve pain and lower fever) may increase the risk of bleeding.

For information on medicines that should not be physically mixed with Rapilysin solution for

injection, see section 3.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor for advice before taking this medicine.

Pregnancy

There is no experience with Rapilysin in pregnant women. Therefore it should not be used except in

life-threatening situations. You must tell your doctor if you are pregnant or think you are pregnant.

Your doctor can tell you the risks and benefits of using Rapilysin during pregnancy.

Breast-feeding

You should not breast-feed your baby during treatment with Rapilysin as it is not known whether

Rapilysin is excreted into mother’s milk. Mother’s milk should be thrown away during the first 24

hours after thrombolytic treatment. Discuss with your doctor when you can take up breast-feeding

again.

3.

How to use Rapilysin

Rapilysin is usually given in a hospital. The medicine is supplied in vials as a powder for injection.

Before use, the powder for injection must be dissolved in the water for injection supplied in the

prefilled syringe that is in the package. Do not add any other medicines. The resulting solution must be

used immediately. The solution must be examined to ensure that only clear, colourless solution is

injected. If the solution is not clear and colourless it should be thrown away.

Treatment with Rapilysin 10 U should be started as soon as possible after the symptoms of heart attack

begin.

Heparin and Rapilysin cannot be mixed in the same solution

. Other medicines may also not mix well

with Rapilysin. No other medicines should be added to the injection solution (see below). Rapilysin

should be injected preferably through an intravenous line that is used only for the injection of

Rapilysin. No other medicines should be injected through the line reserved for Rapilysin, either at the

same time, or before or after Rapilysin injection. This applies to all medicines including heparin and

acetylsalicylic acid, which are given before and after Rapilysin to reduce the risk of new blood clots

forming.

If the same line has to be used, this line (including Y-line) must be flushed thoroughly with a 0.9 %

sodium chloride or 5 % glucose solution before and after the Rapilysin injection.

Dosage of Rapilysin

Rapilysin is given as a 10 U injection followed by a second 10 U injection 30 minutes later (double

bolus).

Each injection should be given slowly within 2 minutes. The injection must not be given mistakenly

outside the vein. Therefore, be sure to tell the medical staff if you experience pain during the injection.

Heparin

and acetylsalicylic acid

are given before and after Rapilysin to reduce the risk of new blood

clots forming.

Dosage of Heparin

The recommended dose of heparin is 5000 I.U. given as a single injection before Rapilysin, followed

by an infusion of 1000 I.U. per hour starting after the second Rapilysin injection. Heparin should be

given for at least 24 hours, preferably for 48-72 hours, in order to keep aPTT values 1.5 to 2 times

normal.

Dosage of Acetylsalicylic Acid

The dose of acetylsalicylic acid given before Rapilysin should be at least 250 mg-350 mg and should

be followed by 75-150 mg/day, at least until discharge from hospital.

If more Rapilysin is used than recommended

In the event of overdosage there may be an increased risk of bleeding.

4.

Possible side effects

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

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

Bleeding at the injection site, e.g. blood blister (haematoma)

Chest Pain / angina, low blood pressure and heart failure /shortness of breath may reappear

Burning sensation when Rapilysin is injected

Common side effects (may affect up to 1 in 10 people)

Bleeding in the digestive tract (e.g. bloody or black vomit, or stools) in the gums or in the

urinary or genital tract

Abnormal heart beats (arrhythmias), cardiac arrest, circulatory collapse or another heart attack

may occur

Uncommon side effects (may affect up to 1 in 100 people)

Bleeding around the heart, in the abdomen, the brain or the eyes, under the skin, from the nose

or as coughed up blood

Damage to the heart or heart valves, or a blood clot in the lung, brain or other part of body

mayoccur

hypersensitivity (e.g.

allergic reactions)

Very rare side effects (may affect up to 1 in 10,000 people)

Events related to the nervous system (e.g. epileptic seizure, convulsion, speech disorder,

delirium, agitation, confusion, depression, psychosis)

severe allergic reaction, causing shock or collapse

Side effects of frequency not known (cannot be estimated from the available data)

Blockage of blood vessels due to cholesterol (fat)

Cardiovascular events can be life-threatening or cause death.

Patients with systolic blood pressure over 160 mmHg have a greater risk of bleeding in the brain. The

risk of intracranial bleeding and fatal intracranial bleeding increases with increasing age. Blood

transfusions were rarely required. Death or permanent disability are not uncommon in patients who

have a stroke (including bleeding in the brain) or other serious bleeding problem.

Be sure to tell hospital staff immediately if any of these symptoms appear.

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.

5.

How to store Rapilysin

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 on the label of the vial

after EXP. The expiry date refers to the last day of that month.

Do not store above 25 °C.

Keep the vial in the outer carton in order to protect from light.

After reconstitution (“when dissolved”), the solution must be used immediately.

6.

Contents of the pack and other information

What Rapilysin contains

The active substance is reteplase 10U/10 ml after reconstitution.

The other ingredients are:

Powder:

Tranexamic acid

di-potassium-hydrogen phosphate

phosphoric acid

sucrose

polysorbate 80

Solvent:

10 ml Water for injection (prefilled syringe)

What Rapilysin looks like and contents of the pack

Rapilysin is presented as a powder and a solvent for injection (0.56 g powder in a vial and 10 ml

solvent in a pre-filled syringe with a reconstitution spike and a needle-pack of 2)

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Actavis Group PTC ehf

Reykjavíkurvegi 76-78

220 Hafnarfjordur

Iceland.

Manufacturer

Actavis Italy S.p.A.

Nerviano Plant

Via Pasteur 10

20014 Nerviano (Milan)

Italy

Cenexi

52, Rue Marcel et Jacques Gaucher

94120 Fontenay-Sous-Bois

France

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

Authorisation Holder:

België/Belgique/Belgien

Actavis Group PTC ehf.

IJsland / Islande / Island

Lietuva

UAB "Sicor Biotech"

Tel: +370 5 266 0203

България

Актавис ЕАД

Teл.: +359 2 489 95 85

Luxembourg/Luxemburg

Actavis Group PTC ehf.

Islande / Island

Česká republika

Teva Pharmaceuticals CR, s.r.o.

Tel: +420 251 007 111

Magyarország

Teva Gyógyszergyár Zrt

Tel.: +36 1 288 6400

Danmark

Teva Denmark A/S

Tlf: +45 44985511

Malta

Actavis Ltd.

Tel: +35621693533

Deutschland

PUREN Pharma GmbH & Co. KG

Tel: +49 (0)89 558909 0

Nederland

Actavis Group PTC ehf.

IJsland

Eesti

UAB "Sicor Biotech" Eesti filiaal

Tel: +372 661 0801

Norge

Teva Norway AS

Tlf: +47 66 77 55 90

Ελλάδα

Specifar ABEE

Τηλ: +30 2105401500

Österreich

ratiopharm Arzneimittel Vertriebs-GmbH

Tel: +43(0)1 97007 0

España

Actavis Group PTC ehf.

Islandia

Polska

Teva Pharmaceuticals Polska Sp. Z o.o.

Tel. +48 22 345 93 00

France

Actavis Group PTC ehf.

Islande

Portugal

Generis Farmacêutica, S.A.

Tel: + 351 214967120

Hrvatska

Pliva Hrvatska d.o.o.

Tel: +385 1 37 20 000

România

Teva Pharmaceuticals S.R.L

Tel: +40 21 230 65 24

Ireland

Teva Pharmaceuticals Ireland

Tel: +353 51 321740

Slovenija

Pliva Ljubljana d.o.o.

Tel: +386 1 58 90 390

Ísland

Actavis Group PTC ehf.

Sími: +354 550 3300

Slovenská republika

TEVA Pharmaceuticals Slovakia s.r.o

Tel: +421 2 57 26 79 11

Italia

Actavis Group PTC ehf.

Islanda

Suomi/Finland

ratiopharm Oy

Puh/Tel: +358 (0) 20 180 5900

Kύπρος

Specifar ABEE

Τηλ: +30 2105401500

Ελλάδα

Sverige

Teva Sweden AB

Tel: +46 42 12 11 00

Latvija

UAB "Sicor Biotech" filiāle Latvijā

Tel: +371 673 23 666

United Kingdom

Actavis UK Limited

Tel: +44 1271 385257

This leaflet was last revised in <

MM/YYYY

}>

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu

---------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

Instructions for use/handling

Incompatibility of some prefilled glass syringes (including Rapilysin) with certain needle free

connectors has been reported. Therefore, the compatibility of the glass syringe and intravenous access

should be ensured before use. In case of incompatibility an adaptor can be used and removed together

with the glass syringe immediately after administration

Use aseptic technique throughout.

Remove the protective flip-cap from the vial of Rapilysin 10 U and clean the rubber closure

with an alcohol wipe.

Open the package containing the reconstitution spike, remove both protective caps from the

reconstitution spike.

Insert the spike through the rubber closure into the vial of Rapilysin 10 U.

Take the 10 ml syringe out of the package. Remove the tip cap from the syringe. Connect the

syringe to the reconstitution spike and transfer the 10 ml of solvent into the vial of Rapilysin

10 U.

With the reconstitution spike and syringe still attached to the vial, swirl the vial gently to

dissolve the Rapilysin 10 U powder. DO NOT SHAKE.

The reconstituted preparation results in a clear, colourless solution. If the solution is not clear

and colourless it should be discarded.

Withdraw 10 ml of Rapilysin 10 U solution back into the syringe. A small amount of solution

may remain in the vial due to overfill.

Disconnect the syringe from the reconstitution spike. The dose is now ready for intravenous

administration.

No other medicines should be injected through the line reserved for Rapilysin either at the same

time, or prior to, or following Rapilysin injection. This applies to all products including heparin

and acetylsalicylic acid, which should be administered before and following the administration

of reteplase to reduce the risk of re-thrombosis.

In those patients where the same line has to be used, this line (including Y-line) must be flushed

thoroughly with a 0.9 % sodium chloride or 5 % glucose solution prior to and following the

Rapilysin injection.