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BIVALIRUDIN 250 MG POWDER FOR CONCENTRATE FOR SOLUTION FOR INJECTION OR INFUSION

Active substance(s): BIVALIRUDIN

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297 x 630 mm
297 mm
SANGRADO ≥ 2 mm

similar to the ones that remind you of your cardiac event
and resulted in your hospitalisation.
Package leaflet: Information for the user

Bivalirudin 250 mg powder for
concentrate for solution for
injection or infusion
bivalirudin
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
pharmacist or nurse.
- If you get any side effects, talk to your doctor or
pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. See section 4.

Other medicines and Bivalirudin
Tell your doctor or pharmacist
• if you are taking/using, or have recently taken/used or
might take/use 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
Bivalirudin. Your warfarin blood test result (INR test) may
be affected by Bivalirudin.
Pregnancy and breast-feeding

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

If you are pregnant or breast-feeding, think you may be
pregnant or are planning to have a baby, ask your doctor
or pharmacist for advice before taking this medicine.

Bivalirudin contains a substance called bivalirudin which
is an antithrombotic medicine. Antithrombotics are
medicines which prevent the formation of blood clots
(thrombosis).
Bivalirudin is used to treat patients:
• with chest pain due to heart disease (acute coronary
syndromes - ACS)
• who are having surgery to treat blockages in their blood
vessels (angioplasty and/or percutaneous coronary
intervention - PCI).

2. What you need to know before you
use Bivalirudin
Do not use Bivalirudin
- if you are allergic to bivalirudin or any of the other
ingredients of this medicine (listed in section 6) or
hirudins (other blood thinning medicines).
- if you have, or have recently had, any bleeding from
your stomach, intestines, bladder or other organs, for
example, if you have noticed abnormal blood in your
stools or urine (except from menstrual bleeding).
- if you have, or have had, difficulty with your blood
clotting (a low platelet count).
- if you have severe high blood pressure.
- if you have an infection of the heart tissue.
- if you have severe kidney problems or if you need
kidney dialysis.
Check with the doctor if you are unsure.
Warnings and precautions
Talk to your doctor before using Bivalirudin.
• if bleeding occurs (if this happens, treatment with
Bivalirudin will be stopped). Throughout your
treatment, the doctor will check you for any signs of
bleeding.
• if you have been treated before with medicines similar
to Bivalirudin (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).

630 mm

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

What is in this leaflet:

1. What Bivalirudin is and what it is
used for

After being treated with Bivalirudin 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

The following information is intended for healthcare
professionals only:
Healthcare professionals should refer to the Summary of
Product Characteristics for full prescribing information.
Bivalirudin 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.
Bivalirudin 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.
Bivalirudin should be administered with acetylsalicylic
acid and clopidogrel.
Instructions for preparation
Aseptic procedures should be used for the preparation
and administration of Bivalirudin.
Add 5 ml sterile water for injections to one vial of
Bivalirudin and swirl gently until completely dissolved
and the solution is clear. Reconstitution may require up
to 3 or 4 minutes to be complete.
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 (0.9%) solution 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.
Reconstituted concentrate for solution for injection or
infusion
pH in the range of the 4.6 to 6.0 and osmolality in the
range of 250 to 450 mOsmol/Kg of the reconstituted
solution (concentration 50 mg/ml).

Bivalirudin 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 Bivalirudin
should be used.
Driving and using machines
The effects of this medicine are known to be short-term.
Bivalirudin is only given when a patient is in hospital. It
is, therefore, unlikely to affect your ability to drive or to
use machines.
Bivalirudin contains sodium
This medicine contains less than 23 mg of sodium per
vial, which means that it is essentially “sodium-free”.

3. How to use Bivalirudin
Your treatment with Bivalirudin will be supervised by a
doctor. The doctor will decide how much Bivalirudin 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:

The doctor will decide for how long you should be
treated.
Bivalirudin 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 use more Bivalirudin than you should
Your doctor will decide how to treat you, including
stopping the drug and monitoring for signs of ill effects.
If you have 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:
- while you are in hospital: tell the doctor or nurse
immediately –
- after you’ve left hospital: contact your doctor
directly or go immediately to the Emergency
Department of your nearest hospital
The common, (may affect up to 1 in 10 people) serious
side effect of treatment with bivalirudin, 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
bivalirudin is used in combination with other
anticoagulant or antithrombotic medicines (see section 2
‘Other medicines and Bivalirudin.

If you need to have a coronary artery bypass graft
operation, treatment with bivalirudin will either be
stopped 1 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

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

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.

are to be medically managed may continue the infusion
of 0.25 mg/kg/h for up to 72 hours.
If the medically managed patient proceeds to PCI, an
additional bolus of 0.5 mg/kg of bivalirudin should be
administered before the procedure and the infusion
increased to 1.75 mg/kg/h for the duration of the procedure.
Following PCI, the reduced infusion dose of 0.25 mg/kg/h
may be resumed for 4 to 12 hours as clinically necessary.

• 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 vein of 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 weight per hour for an
additional 4 to 12 hours.

Contraindications
Bivalirudin 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. (see section 4.3 of SmPC).
Posology
Patients undergoing PCI, including primary PCI
The recommended dose of bivalirudin for patients
undergoing PCI is an intravenous bolus of 0.75 mg/kg
body weight followed immediately by an intravenous
infusion at a rate of 1.75 mg/kg body weight/hour for at
least the duration of the procedure. The infusion of 1.75
mg/kg body weight/hour may be continued for up to 4
hours post-PCI as clinically warranted and in STEMI
patients should be continued for up to 4 hours post-PCI
(see section 4.4). The infusion may be continued at a
reduced dose of 0.25 mg/kg/h for an additional 4 – 12
hours as clinically necessary.
Patients should be carefully monitored following primary
PCI for signs and symptoms consistent with myocardial
ischaemia.
Patients with unstable angina/non-ST segment elevated
myocardial infarction (UA/NSTEMI)

Incompatibilities

The recommended starting dose of bivalirudin for
medically managed patients with acute coronary
syndrome (ACS) is an intravenous bolus of 0.1 mg/kg
followed by an infusion of 0.25 mg/kg/h. Patients who

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In the elderly, if their kidney function is decreased, the
dose may need to be reduced.

• 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 serious 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).

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

The following medicinal products should not be
administered in the same intravenous line as bivalirudin

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

For patients who proceed to coronary artery bypass graft
(CABG) surgery off pump, the intravenous infusion of
bivalirudin should be continued until the time of surgery.
Just prior to surgery, a 0.5 mg/kg bolus dose should be
administered followed by a 1.75 mg/kg/h intravenous
infusion for the duration of the surgery.
For patients who proceed to CABG surgery on pump,
the intravenous infusion of bivalirudin should be
continued until 1 hour prior to surgery after which the
infusion should be discontinued and the patient treated
with unfractionated heparin (UFH).
To ensure appropriate administration of bivalirudin, the
completely dissolved, reconstituted and diluted product
should be thoroughly mixed prior to administration (see
section 6.6). The bolus dose should be administered by
a rapid intravenous push to ensure that the entire bolus
reaches the patient before the start of the procedure.
Intravenous infusion lines should be primed with
bivalirudin to ensure continuity of drug infusion after
delivery of the bolus.
The infusion dose should be initiated immediately after
the bolus dose is administered, ensuring delivery to the
patient prior to the procedure, and continued
uninterrupted for the duration of the procedure. The safety
and efficacy of a bolus dose of bivalirudin without the
subsequent infusion has not been evaluated and is not
recommended even if a short PCI procedure is planned.
An increase in the activated clotting time (ACT) may be
used as an indication that a patient has received
bivalirudin.
Renal insufficiency
Bivalirudin is contraindicated in patients with severe
renal insufficiency (GFR<30 ml/min) and also in
dialysis-dependent patients (see section 4.3).
In patients with mild or moderate renal insufficiency, the
ACS dose (0.1 mg/kg bolus/0.25 mg/kg/h infusion)
should not be adjusted.
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Children and adolescents

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.

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297 x 630 mm
297 mm
SANGRADO ≥ 2 mm

- 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 your
doctor go immediately to the Emergency
Department of your nearest hospital -

Not all pack sizes may be marketed.

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

Accord Healthcare Limited
Sage House, 319 Pinner Road,
North Harrow, Middlesex, HA1 4HF,
United Kingdom

Common side effects (may affect 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)
Rare side effects (may affect up to 1 in 1,000 people)
• INR test (warfarin blood test result) increased (see
Section 2, Other medicines and Bivalirudin)
• 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

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Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:

Manufacturers:
Laboratory Reig Jofré S.A.
C/Gran Capitán, 10, Sant Joan Despí,
08970 Barcelona
Spain
Accord Healthcare Limited
Sage House, 319 Pinner Road,
North Harrow, Middlesex, HA1 4HF,
United Kingdom
This leaflet was last revised in 05/2016.

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

5. How to store Bivalirudin
As Bivalirudin is a hospital only medicine, storage of
Bivalirudin 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 after ‘EXP’. The expiry
date refers to the last day of that month.
Reconstituted solution: Store at 2-8 ºC in a refrigerator.
Do not freeze.
Diluted solution: Do not store above 25°C. Do not
refrigerate. Do not freeze.
The solution should be a clear to slightly opalescent,
colourless to slightly yellow solution.
The doctor will check the solution and will discard it, if it
contains particles or is discoloured.

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

630 mm

- 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 (E421) and sodium
hydroxide (for pH adjustment)
What Bivalirudin looks like and contents of the pack
Bivalirudin is a powder for concentrate for solution for
injection or infusion (powder for concentrate).
Bivalirudin is a sterile, white to off-white powder in a
glass vial.
Bivalirudin is available in cartons containing 1 vial, 5 vials
or 10 vials.

Patients with moderate renal impairment (GFR 30-59
ml/min) undergoing PCI (whether being treated with
bivalirudin for ACS or not) should receive a lower
infusion rate of 1.4 mg/kg/h. The bolus dose should not
be changed from the posology described under ACS or
PCI above.
Hepatic impairment
No dose adjustment is needed.
(For full information on posology see section 4.2 of
SmPC)
Shelf life
3 years
Reconstituted solution: Chemical and physical in-use
stability has been demonstrated for 24 hours at
2-8°C. Store at 2-8 ºC in a refrigerator. 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, in-use storage times and
conditions are the responsibility of user.
Diluted solution: Chemical and physical in-use stability
has been demonstrated for 24 hours at 25°C. Do not
store above 25°C. Do not refrigerate. 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, in-use storage
times and conditions are the responsibility of user.

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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