Bivalirudina Accord

Leaflet accompanying the packaging: patient information

Biwalirudyna Accord, 250 mg, powder for concentrate for solution for injection/infusion

for injection/infusion
Bivalirudinum

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What is Biwalirudyna Accord and what is it used for
• 2. Important information before using Biwalirudyna Accord
• 3. How to use Biwalirudyna Accord
• 4. Possible side effects
• 5. How to store Biwalirudyna Accord
• 6. Package contents and other information

1. What is Biwalirudyna Accord and what is it used for

Biwalirudyna Accord contains the active substance bivalirudin, which is an anticoagulant. Anticoagulants prevent the formation of blood clots (thrombosis).
Biwalirudyna Accord is used to treat patients:

• with chest pain caused by heart disease (Acute Coronary Syndrome - ACS),
• who are undergoing interventional treatment of clogged blood vessels (angioplasty and/or percutaneous coronary intervention - PCI).

2. Important information before using Biwalirudyna Accord

When not to use Biwalirudyna Accord

• if the patient is allergic to bivalirudin or any of the other ingredients of this medicine (listed in section 6) or to hirudin derivatives (other blood thinning medicines),
• if the patient has or has recently had bleeding from the stomach, intestines, bladder, or other internal organs, such as blood in the stool or urine (not including menstruation),
• if the patient has or has had blood clotting disorders (low platelet count),
• if the patient has high blood pressure,
• if the patient has a heart tissue infection,
• in cases of severe kidney disease or in patients undergoing dialysis.

In case of doubts, consult a doctor.

Warnings and precautions

Before starting treatment with Biwalirudyna Accord, discuss it with your doctor.

• if bleeding occurs (in which case treatment with Biwalirudyna Accord will be discontinued); during the entire treatment period, the doctor will monitor the patient's condition, looking for any signs of bleeding;
• if the patient has been treated with medicines similar to Biwalirudyna Accord (e.g., lepirudin);
• before starting injection or intravenous infusion, the doctor will inform the patient about the symptoms of an allergic reaction; such reactions occur infrequently (may occur in no more than 1 in 100 people);
• if the patient is undergoing radiation therapy in the area of blood vessels supplying the heart (treatment called brachytherapy with beta or gamma rays).

After receiving Biwalirudyna Accord due to a coronary incident, the patient should remain in the hospital for at least 24 hours and should be monitored for any symptoms or signs of a recurrent coronary incident that led to hospitalization.

Children and adolescents

• the use of this medicine in children (under 18 years of age) is not appropriate

Biwalirudyna Accord and other medicines

Tell your doctor or pharmacist about:

• all medicines you are currently taking or have recently taken, as well as any medicines you plan to take
• all blood thinning medicines or medicines that prevent blood clots (anticoagulants or antiplatelet agents, e.g., warfarin, dabigatran, apixaban, rivaroxaban, acetylsalicylic acid, clopidogrel, prasugrel, ticagrelor).

These medicines, when given together with Biwalirudyna Accord, may increase the risk of bleeding.
Biwalirudyna Accord may affect the normalized international ratio (INR).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before using this medicine.
Biwalirudyna Accord should not be used during pregnancy unless it is absolutely necessary. The treating doctor will decide if it is necessary. During breastfeeding, the doctor will decide whether Biwalirudyna Accord should be used.

Driving and using machines

The effects of this medicine are known and are short-lived. Biwalirudyna Accord is used only when the patient is in the hospital. Therefore, it is unlikely that the medicine will affect the ability to drive and use machines.

Biwalirudyna Accord contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial, which means it is essentially "sodium-free".

3. How to use Biwalirudyna Accord

Treatment with Biwalirudyna Accord is carried out under the supervision of a doctor. The doctor decides what dose of the medicine to use and prepares the medicine.
The dose of the medicine depends on the patient's weight and the type of treatment.

Dosage

In the case of patients with acute coronary syndromes (ACS) treated pharmacologically, the recommended initial dose is:

• 0.1 mg/kg body weight in intravenous injection, followed by intravenous infusion at a dose of 0.25 mg/kg body weight per hour for up to 72 hours.

If it is stillnecessary to perform percutaneous coronary intervention (PCI), the dosage should be increased to:

• 0.5 mg/kg body weight in intravenous injection, followed by intravenous infusion at a dose of 1.75 mg/kg body weight per hour for the duration of the PCI.
• after the procedure is completed, the infusion can be continued at a reduced dose of 0.25 mg/kgbody weight per hour for an additional 4 to 12 hours.

In case of coronary artery bypass grafting (CABG), treatment with bivalirudin should be discontinued 1 hour before the procedure or an additional dose of 0.5 mg/kg body weight should be administered in intravenous injection, followed by intravenous infusion at a dose of 1.75 mg/kg body weight per hour for the duration of the procedure.

For patients starting percutaneous coronary intervention (PCI), the recommended dosage is:

• 0.75 mg/kgbody weight in intravenous injection, followed by immediate intravenous infusion at a dose of 1.75 mg/kgbody weight per hour for at least the duration of the PCI. The intravenous infusion can be continued at this dose for up to 4 hours after the completion of the PCI, and in patients with ST-segment elevation myocardial infarction (STEMI) (a severe type of heart attack), the infusion should be continued at this dose for up to 4 hours. After this infusion, a reduced dose of 0.25 mg/kg body weight per hour can be administered for an additional 4 to 12 hours.

If there are kidney problems, the dose of Biwalirudyna Accord may need to be reduced.
In elderly patients, a dose reduction may be necessary in case of impaired renal function.
The doctor must decide on the duration of treatment.
Biwalirudyna Accord is administered intravenously, followed by intravenous infusion (never intramuscularly). The medicine is administered under the control of a doctor experienced in the treatment of patients with heart diseases.

Using a higher dose of the medicine than recommended

The doctor will decide on the treatment, including discontinuing the medicine and monitoring the patient for signs of side effects.
In case of any further doubts about the use of this medicine, consult a doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If any of the following potentially serious side effects occur:

• during hospitalization: report them immediately to the doctor or nurse;
• after discharge from the hospital: contact the attending doctor or go immediately to the nearest hospital emergency department

The most common (may occur in no more than 1 in 10 people) serious side effect related to bivalirudin treatment is major bleeding, which can occur in any part of the body (e.g., stomach, gastrointestinal tract (including bloody vomiting or blood in the stool), abdomen, lungs, groin, bladder, heart, eye, ear, nose, or brain). It may rarelylead to stroke or death. Swelling or pain in the groin or arm, back pain, bruising, headache, bloody sputum, urine with a pink or red color, sweating, feeling of weakness or fainting, or dizziness due to low blood pressure may be signs of internal bleeding. The occurrence of bleeding is more likely when bivalirudin is used in combination with other anticoagulant or antiplatelet agents (see section 2 "Biwalirudyna Accord and other medicines").

• Bleeding and bruising at the injection site (after PCI), which may be accompanied by pain. In rare cases, it may require surgical intervention to repair the blood vessel in the groin (fistula, pseudoaneurysm) (may occur in no more than 1 in 1,000 people). Not very common (may occur in no more than 1 in 100 people) is a decreased platelet count, which can lead to increased bleeding. Gingival bleeding (not very common, may occur in no more than 1 in 100 people) is usually not serious.
• Allergic reactions occur not very commonly (may occur in no more than 1 in 100 people) and are usually not serious, but can become serious in certain circumstances and, in rare cases, can be fatal due to a drop in blood pressure (shock). They may start with symptoms occurring in a limited area, such as itching, redness of the skin, rash, or small bumps on the skin. Sometimes reactions can be more severe with itching of the throat, feeling of pressure in the throat, swelling of the eyes, face, tongue, or lips, with a piercing whistle during inhalation (wheezing), difficulty breathing or during exhalation (stridor).
• Thrombosis (blood clot) is a not very common side effect (may occur in no more than 1 in 100 people), which can lead to serious, even fatal complications, such as a heart attack. Thrombosis includes coronary artery thrombosis (clot in the heart arteries or in the stent, felt as a heart attack, which can also be fatal) and (or) catheter-related thrombosis, both of which occur rarely (may occur in no more than 1 in 1,000 people).

If any of the following (potentially less serious) side effects occur:

• during hospitalization, report them immediately to the doctor or nurse;
• after discharge from the hospital: first consult your doctor. If this is not possible, go immediately to the nearest hospital emergency department

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

• Minor bleeding

Common side effects (may occur in no more than 1 in 10 people):

• Anemia (low red blood cell count)
• Hematoma (bruising)

Not very common side effects (may occur in no more than 1 in 100 people):

• Nausea and/or vomiting

Rare side effects (may occur in no more than 1 in 1,000 people):

• Increased INR (normalized international ratio) (see section 2, Biwalirudyna Accord and other medicines)
• Chest pain or chest discomfort
• Slow heart rate
• Fast heart rate
• Shortness of breath
• Reperfusion injury (incomplete or no return of blood flow): impaired blood flow in the heart arteries after restoring circulation

Reporting side effects

If you experience any side effects, including any side effects not listed in the leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Biwalirudyna Accord

Since Biwalirudyna Accord is a medicine intended for hospital use only, the storage of Biwalirudyna Accord is the responsibility of medical personnel.
The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after: EXP.
The expiry date refers to the last day of the month stated.
Reconstituted solution: store in a refrigerator (2–8 ºC). Do not freeze.
Diluted solution: do not store above 25°C. Do not store in a refrigerator. Do not freeze.
The solution should be clear to slightly opalescent, colorless to slightly yellow.
The doctor will check the solution before administration and discard it if it contains particles or has changed color.

6. Package contents and other information

What Biwalirudyna Accord contains

• The active substance of the medicine is bivalirudin.
• Each vial contains 250 mg of bivalirudin.
• After reconstitution of the medicine (adding 5 ml of water for injections to the vial to dissolve the powder) 1 ml of the solution contains 50 mg of bivalirudin.
• After dilution (mixing 5 ml of the reconstituted solution in an infusion bag [with a total volume of 50 ml] containing glucose solution or sodium chloride solution) 1 ml of the solution contains 5 mg of bivalirudin.

Other ingredients are: mannitol (E 421) and sodium hydroxide (to adjust the pH to 4.5-5.5)

What Biwalirudyna Accord looks like and contents of the pack

Biwalirudyna Accord is a powder for concentrate for solution for injection/infusion (powder for concentrate).
Biwalirudyna Accord is a white or almost white powder in a glass vial.
Biwalirudyna Accord is available in cardboard boxes containing 1, 5, or 10 vials.
Not all pack sizes may be marketed.

Marketing authorization holder:

Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warsaw
Tel: +48 22 577 28 00

Manufacturer:

Laboratory Reig Jofré S.A.
C/Gran Capitán, 10, Sant Joan Despí
08970 Barcelona
Spain

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Date of last revision of the leaflet: August 2024

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The following information is intended for healthcare professionals only.
Healthcare professionals should consult the full information about the medicine contained in the Summary of Product Characteristics.
Biwalirudyna Accord is indicated as an anticoagulant for use in adult patients undergoing percutaneous coronary intervention (PCI), including patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI.
Biwalirudyna Accord is also indicated in adult patients with unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI) who are planned for urgent or early interventional treatment.

Preparation

Biwalirudyna Accord should be prepared and administered in accordance with aseptic principles.
Add 5 ml of sterile water for injections to one vial and gently rotate the vial until the product is completely dissolved, and the solution is clear.
Draw up 5 ml of the solution from the vial and further dilute in a total volume of 50 ml of glucose 5% solution for injection or 9 mg/ml (0.9%) sodium chloride solution for injection to achieve a final concentration of bivalirudin of 5 mg/ml.
The reconstituted solution/diluted solution should be inspected for particulate matter or discoloration. Solution containing particulate matter or discoloration should not be used.
The reconstituted solution/diluted solution should be clear or slightly opalescent, colorless to slightly yellow.

Pharmaceutical incompatibilities

The following medicines should not be administered through the same intravenous line as bivalirudin, as they may cause precipitation, formation of particulate matter, or increased particle size: alteplase, amiodarone hydrochloride, amphotericin B, chlorpromazine hydrochloride, diazepam, prochlorperazine edisylate, reteplase, streptokinase, and vancomycin hydrochloride.
Six medicinal products have been shown to be incompatible with bivalirudin in a concentration-dependent manner. A list of concentrations that are compatible or incompatible can be found in section 6.2. Medicinal products that are incompatible with bivalirudin at higher concentrations include dobutamine hydrochloride, famotidine, haloperidol lactate, labetalol hydrochloride, lorazepam, and promethazine hydrochloride.

Contraindications

Biwalirudyna Accord is contraindicated in patients:

• with known hypersensitivity to the active substance or to any of the excipients listed in section 6.1, or to hirudin
• with active bleeding or increased risk of bleeding due to hemostasis disorders and/or irreversible coagulation disorders
• with uncontrolled, severe hypertension
• with acute bacterial endocarditis
• with severe renal impairment (GFR <30 ml min) and in patients undergoing dialysis (see summary of product characteristics, section 4.3)< li>

Dosage

Patients undergoing percutaneous coronary intervention (PCI), including patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI
The recommended dose of bivalirudin for patients undergoing PCI is 0.75 mg/kg body weight in intravenous bolus, immediately followed by intravenous infusion at 1.75 mg/kg body weight per hour for at least the duration of the procedure. The infusion can be continued at 1.75 mg/kg body weight per hour for up to 4 hours after the completion of PCI and at a reduced dose of 0.25 mg/kg body weight per hour for an additional 4 to 12 hours, if clinically justified.
Patients who have undergone primary PCI should be closely monitored for subjective and objective signs of myocardial ischemia.
Patients with unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI)
The recommended initial dose of bivalirudin for patients with acute coronary syndrome (ACS) treated pharmacologically is 0.1 mg/kg body weight in intravenous bolus, followed by intravenous infusion at 0.25 mg/kg/h. Patients who require continued treatment may receive the product in intravenous infusion at 0.25 mg/kg/h for up to 72 hours.
Ifa patient treated pharmacologically is prepared for PCI, an additional intravenous bolus of bivalirudin should be administered at a dose of 0.5 mg/kg body weight, followed by intravenous infusion at 1.75 mg/kg body weight per hour during the procedure. After the procedure, the medicine can be administered at a reduced dose of 0.25 mg/kg body weight per hour for 4 to 12 hours, if clinically justified.
In patients prepared for coronary artery bypass grafting (CABG) without cardiopulmonary bypass, bivalirudin infusion should be continued until the procedure. Before the procedure, the product should be administered in intravenous bolus at a dose of 0.5 mg/kg body weight, followed by intravenous infusion at 1.75 mg/kg body weight per hour during the procedure.
In patients prepared for CABG with cardiopulmonary bypass, the bivalirudin infusion should be discontinued 1 hour before the procedure, and the patient should receive unfractionated heparin (UFH).
To ensure proper administration of bivalirudin, the fully reconstituted and diluted product should be thoroughly mixed (see section 6.6) before administration. The administration of the product in intravenous bolus should be decided and rapid to ensure that the entire bolus reaches the patient before the start of the procedure.
Intravenous lines should be filled with bivalirudin to ensure continuity of infusion after the bolus administration.
Infusion should be started immediately after bolus administration to ensure that the infusion of the product to the patient starts before the procedure and continues uninterrupted throughout the procedure. The safety and efficacy of administering a bolus dose of bivalirudin without subsequent infusion have not been established and are not recommended, even if a short PCI procedure is planned.
The increase in activated clotting time (ACT) may be used as an indicator to confirm that the patient has received bivalirudin.
Renal impairment
Biwalirudyna Accord is contraindicated in patients with severe renal impairment (GFR <30 ml min), as well in patients undergoing dialysis (see section 4.3).
In patients with mild or moderate renal impairment treated for ACS, the dose (0.1 mg/kg body weight in intravenous bolus/0.25 mg/kg/h in intravenous infusion) does not need to be adjusted.
In patients with moderate renal impairment (GFR 30-59 ml/min) undergoing PCI (regardless of whether they received bivalirudin for ACS or not), the infusion rate should be reduced to 1.4 mg/kg body weight per hour. The bolus dose should remain at the same level as described in the dosing for ACS or PCI.
Hepatic impairment
Dose adjustment is not necessary.

Shelf life

3 years
Reconstituted solution: the chemical and physical stability of the solution has been demonstrated for 24 hours when stored at 2–8 ºC. Store in a refrigerator (2–8 ºC). Do not freeze. From a microbiological point of view, unless the method of opening/reconstitution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the user of the product is responsible for the storage conditions prior to use.
Diluted solution: the chemical and physical stability of the solution has been demonstrated for 24 hours when stored at 25 ºC.
Do not store above 25 ºC. Do not store in a refrigerator. Do not freeze. From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the user of the product is responsible for the storage conditions prior to use.