Angiox - patient leaflet, side effects, dosage

WHAT ANGIOX IS AND WHAT IT IS USED FOR

WHAT YOU NEED TO KNOW BEFORE YOU USE ANGIOX

• if you have been treated before with medicines similar to Angiox (e.g. lepirudin).
• before the start of the injection or infusion, the doctor will tell you about the signs of allergic

reaction. Such a reaction is uncommon (may affect up to 1 in 100 people).

• if you are having radiation treatment in the vessels that supply blood to the heart (treatment

called beta or gamma brachytherapy).

After being treated with Angiox for a cardiac event, you should stay in the hospital for at least 24 hours and you should be monitored for any symptoms or signs similar to the ones that remind you of your cardiac event and resulted in your hospitalisation.

Children and adolescents

• if you are a child (less than 18 years of age), this medicine is not appropriate for you.

Other medicines and Angiox tell your doctor

if you are taking, or have recently taken or might take any other medicines.

If you are taking blood thinners or medicines to prevent blood clots (anticoagulants or antithrombotics e.g. warfarin, dabigatran, apixaban, rivaroxaban, acetylsalicylic acid, clopidogrel, prasugrel, ticagrelor).

these medicines may increase the risk of side effects such as bleeding when given at the same time as Angiox. Your warfarin blood test result (INR test) may be affected by Angiox.

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.

Angiox should not be used during pregnancy, unless clearly necessary. Your doctor will decide whether or not this treatment is appropriate for you. If you are breast-feeding, the doctor will decide whether Angiox should be used.

Driving and using machines nown to be short-term. Angiox is only given when a patient is in to affect your ability to drive or to use machines.

Angiox contains sodium

This medicine contains less than 23 mg of sodium per vial, which means that it is essentially “sodium-free”.

HOW TO USE ANGIOX

Your treatment with Angiox will be supervised by a doctor. The doctor will decide how much Angiox you receive, and will prepare the medicine.

The dose given depends on your weight and on the kind of treatment you are being given.

Dosage

For patients with acute coronary syndromes (ACS) who are treated medically the recommended starting dose is:

• 0.1 mg/kg body weight as an intravenous injection, followed by an infusion (drip) into vein of

0.25 mg/kg body weight per hour for up to 72 hours.

If, after this, you then need percutaneous coronary intervention (PCI) treatment, the dosage will be increased to:

• 0.5 mg/kg body weight for the intravenous injection, followed by an infusion into

• 1.75 mg/kg body weight, per hour for the duration of the PCI.

• When this treatment is finished, the infusion may go back to 0.25 mg/kg body we

for an additional 4 to 12 hours.

If you need to have a coronary artery bypass graft operation, treatment with bivalirudin will either be stopped one hour before the operation or an additional dose of 0.5 mg/kg body weight will be given by injection followed by an infusion of 1.75 mg/kg body weight per hour for the duration of surgery.

For patients starting with percutaneous coronary intervention (PCI) the recommended dose is:

• 0.75 mg/kg body weight as an intravenous injection, followed immediately by an infusion (drip)

into vein of 1.75 mg/kg body weight, per hour for at least the duration of the PCI. The intravenous infusion may continue at this dose for up to 4 hours after the PCI and for STEMI patients (those with a severe type of heart attack) it should continue at this dose for up to 4 hours. The infusion may be followed by an infusion at a lower dose of 0.25 mg/kg body weight for an additional 4 to 12 hours.

If you have kidney problems, the dose of Angiox may need to be reduced.

The doctor will decide for how l

Angiox is for injection, followed by infusion (drip), into a vein (never into a muscle). This is administered and supervised by a doctor experienced in caring for patients with heart disease.

If you receive more of this medicine than you should

Your doctor will decide how to treat you, including stopping the drug and monitoring for signs of ill effects.

any further questions on the use of this medicine, ask your doctor.

4. POSSIBLE SIDE EFFECTS

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

If you get any of the following, potentially serious, side effects:

o while you are in hospital: tell the doctor or nurse immediately -

o after you’ve left hospital: contact your doctor directly or go immediately to the Emergency

Department of your nearest hospital -

The most common, (may affect up to 1 in 10 people) serious side effect of treatment with Angiox, is major bleeding which could occur anywhere inside the body (e.g. stomach, digestive system (including vomiting blood or passing blood with the stools), abdomen, lungs, groin, bladder, heart, eye, ear, nose or brain). This may, rarely , result in a stroke or be fatal. Swelling or pain in the groin or the arm, back pain, bruising, headache, coughing blood, pink or red urine, sweating, feeling faint or sick or dizzy due to low blood pressure may be signs of internal bleeding. Bleeding is more likely to occur when Angiox is used in combination with other anticoagulant or antithrombotic medicines (see section 2 ‘Taking other medicines’).

Bleeding and bruising at the puncture site (after PCI treatment) may be painful. Rarely this may require surgery to repair the blood vessel in the groin (fistula, pseudoaneurysm) (may affect up to 1 in 1,000 people). Uncommonly (may affect up to 1 in 100 people) the number of blood platelets may be low which can worsen any bleeding. Gum bleeding (uncommon, may affect up to 1 in 100 people) is usually not serious.

Allergic reactions,– are uncommon (may affect up to 1 in 100 people) and usually not erious but can become severe under some circumstances, and in rare cases may be fatal due to low blood pressure (shock). They may begin with limited symptoms such as itching, redness of the skin, rash or small bumps on the skin. Occasionally, reactions can be more severe with throat itching, throat tightening, swelling of the eyes, face, tongue or lips, high pitched whistling during inhaling (stridor), difficulty breathing or exhaling (wheezes).

Thrombosis (blood clot) is an uncommon side effect (may affect up to 1 in 100 people) which may result in serious or fatal complications such as heart attack. Thrombosis includes coronary artery thrombosis (blood clot in the heart arteries or within a stent being felt as a heart attack which can also be fatal) and/or thrombosis in the catheter, both of which are rare (may affect up to 1 in 1,000 people).

If you get any of the following, (potentially less serious), side effects:

while you are in hospital: tell the doctor or nurse -

after you’ve left hospital: first seek advice from your doctor. If you cannot get access to

mergency Department of your nearest hospital -

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

• Minor bleeding

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

• Anaemia (a low blood cell count)
• Haematoma (bruising)

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

• nausea (feeling sick) and/or vomiting (being sick) effects (may affect up to 1 in 1000 people)

test (warfarin blood test result) increased (see Section 2, Other medicines and Angiox) Angina or chest pain

Slow heartbeat

• Rapid heartbeat
• Shortness of breath
• Reperfusion injury (no or slow reflow): impaired flow in the heart arteries after they have been reopened

Reporting of side effects

If you get any side effects, talk to your doctor. 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 ANGIOX

As Angiox is a hospital only medicine, storage of Angiox is the responsibility of healthcare professionals.

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 label and carton a expiry date refers to the last day of that month.

Lyophilised (freeze-dried) powder: Do not store above 25°C. <

Reconstituted solution: Store in a refrigerator (2–8°C). Do not freeze.

Diluted solution: Do not store above 25°C. Do not freeze.

The solution should be a clear to slightly opalescent, colourless

The doctor will check the solution and will discard it, if it co

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Angiox contains

• – The active substance is bivalirudin.

• – Each vial contains 250 mg bivalirudin.

• – After reconstitution (addition of 5 ml water for injections to the vial to dissolve the powder),

• 1 ml contains 50 mg bivalirudin.

• – After dilution (mixing of 5 ml of the reconstituted solution into an infusion bag [total volume of

50 ml] of glucose solution or sodium chloride solution) 1 ml contains 5 mg bivalirudin.

The other ingredients are mannitol and sodium hydroxide 2% (for pH adjustment)

What Angiox looks like and contents of the pack

Angiox is a powder for concentrate for solution for injection or infusion (powder for concentrate).

Angiox is a white to off-white powder in a glass vial.

Angiox is available in cartons containing 10 vials.

Marketing Authorisation Holder and Manufacturer

The Medicines Company UK Limited

115L Milton Park

Abingdon

Oxfordshire

OX14 4SA

UNITED KINGDOM

Manufacturer

Halsa Pharma GmbH

Nikolaus Durkopp-Str. 4A

33602 Bielefeld

GERMANY

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

EMáSa Ferrer-Galenica A.E. Tql: +30 210 5281700	Österreich The Medicines Company UK Ltd Tel : +43 (0) 800070265 oder +43 (0) 1206092417 E-Mail :
España Ferrer Internacional, S.A. Gran Vía Carlos III, 94 08028-Barcelona Tel.: +34 93 600 37 00	Polska The Medicines Company UK Ltd Tel.: +48 800702695 lub +48 223060790 E-mail:
France The Medicines Company France SAS Tél : +33 (0)805542540 ou + 33 (0)1 41 29 75 75 ou + 33 (0)1 57 32 92 42 Email :	Portugal Ferrer Portugal, S.A. Tel.: +351 21 444 96 00
Hrvatska The Medicines Company UK Ltd Tel: 00800 843 633 26 ili +41 44 828 1084 Email:	Romania The Medicines Company UK Ltd Tel: 00800 843 633 26 sau +41 44 828 1084 E-mail :
Ireland The Medicines Company UK Ltd Tel : +353 1800812065 or +353 (0)19075583 Email :	Slovenija The Medicines Company UK Ltd Tel : +386 (0) 80080631 ali +386 (0) 18888602 E-pošta:
Ísland The Medicines Company UK Ltd Sími : +354 8007260 eóa +41 44 828 1084 Netfang : Italia The Medicines Company UK Ltd Tel: +39 800979546 o +39 (0)291294790 Email:	Slovenská republika The Medicines Company UK Ltd Tel : +421 (0 )268622610 alebo +421 (0) 268622610 Email : Suomi/Finland The Medicines Company UK Ltd Puh./tel. +358 (0) 800774218 tai +358 (0) 972519943 S-posti:
Kúnpo^ THESPIS PHARMACEUTICAL LtdTql: Tql:	Sverige The Medicines Company UK Ltd
+357–22677710	Tfn : +46 (0) 20100527 eller +46 (0) 859366368 E-post :
Latvija The Medicines Company UK Ltd Talr. +371 80004842 vai +371 67859709 E-pasts:	United Kingdom The Medicines Company UK Ltd Tel : +44 (0)800 587 4149 or +44 (0)203 684 6344 Email :

This leaflet was last revised in:

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

The following information is intended for healthcare professionals only:

Healthcare professionals should refer to the Summary of Product Characteristics for full prescribing information.

Angiox is indicated as an anticoagulant in adult patients undergoing percutaneous coronary intervention (PCI), including patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. rv

Angiox is also indicated for the treatment of adult patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI) planned for urgent or early intervention.

Angiox should be administered with acetylsalicylic acid and clopidogrel.

Instructions for preparation

Aseptic procedures should be used for the preparation and

Add 5 ml sterile water for injections to one vial of Angiox and swirl gently until completely dissolved and the solution is clear.

Withdraw 5 ml from the vial, and further dilute in a total volume of 5% 50 ml of glucose solution for injection, or sodium chloride 9 mg/ml olution for injection to give a final bivalirudin

concentration of 5 mg/ml.

The reconstituted/di­luted solution should be inspected visually for particulate matter and discolouration. Solutions containing particulate matter should not be used.

The reconstituted/di­luted solution will be a clear to slightly opalescent, colourless to slightly yellow solution.

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

Incompatibilities

The following medicinal products should not be administered in the same intravenous line as bivalirudin since they result in haze formation, micro-particulate formation or gross precipitation; alteplase, amiodarone HCl, amphotericin B, chlorpromazine hydrochloride (HCl), diazepam, prochlorperazine edisylate, reteplase, streptokinase and vancomycin HCl.

The following six medicinal products show dose-concentration incompatibilities with bivalirudin. See section 6.2 for the summary of compatible and incompatible concentrations of these compounds. The medicinal products incompatible with bivalirudin at higher concentrations are: dobutamine hydrochloride, famotidine, haloperidol lactate, labetalol hydrochloride, lorazepam and promethazine HCl.

Contraindications

Angiox is contraindicated in patients with:

• a known hypersensitivity to the active substance or to any of the excipients listed in section 6.1,

or to hirudins

• active bleeding or increased risk of bleeding because of haemostasis disorders and/or

irreversible coagulation disorders

• severe uncontrolled hypertension
• subacute bacterial endocarditis
• severe renal impairment (GFR<30 ml/min) and in dialysis-dependent patients.