Eptifibatide Accord

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Eptifibatide Accord 0.75 mg/ml solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of solution for infusion contains 0.75 mg of eptifibatide. 
 
One vial of 100 ml of solution for infusion contains 75 mg of eptifibatide. 
 
Excipient with known effect: 
0.75 mg/ml : 1.72 mg/ml (0.075 mmol/ml) sodium 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for infusion. 
 
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Eptifibatide Accord is intended for use with acetylsalicylic acid and unfractionated heparin. 
 
Eptifibatide Accord is indicated for the prevention of early myocardial infarction in adults presenting 
with unstable angina or non-Q-wave myocardial infarction, with the last episode of chest pain 
occurring within 24 hours and with electrocardiogram (ECG) changes and/or elevated cardiac 
enzymes. 
 
Patients most likely to benefit from Eptifibatide Accord treatment are those at high risk of developing 
myocardial infarction within the first 3-4 days after onset of acute angina symptoms including for 
instance those that are likely to undergo an early PTCA (Percutaneous Transluminal Coronary 
Angioplasty) (see section 5.1). 
 
4.2 Posology and method of administration 
 
This product is for hospital use only. It should be administered by specialist physicians experienced in 
the management of acute coronary syndromes. 
 
Eptifibatide Accord solution for infusion must be used in conjunction with Eptifibatide Accord 
solution for injection. 
 
Concurrent administration of heparin is recommended unless this is contraindicated for reasons such 
as a history of thrombocytopenia associated with use of heparin (see ‘Heparin administration’, section 
4.4). Eptifibatide Accord is also intended for concurrent use with acetylsalicylic acid, as it is part of 
standard management of patients with acute coronary syndromes, unless its use is contraindicated. 
 
Posology 
 



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Adults (≥ 18 years of age) presenting with unstable angina (UA) or non-Q-wave myocardial infarction 
(NQMI) 
The recommended dosage is an intravenous bolus of 180 microgram/kg administered as soon as 
possible following diagnosis, followed by a continuous infusion of 2 microgram/kg/min for up to 72 
hours, until initiation of coronary artery bypass graft (CABG) surgery, or until discharge from the 
hospital (whichever occurs first). If Percutaneous Coronary Intervention (PCI) is performed during 
eptifibatide therapy, continue the infusion for 20-24 hours post-PCI for an overall maximum duration 
of therapy of 96 hours. 
 
Emergency or semi-elective surgery 
If the patient requires emergency or urgent cardiac surgery during the course of eptifibatide therapy, 
terminate the infusion immediately. If the patient requires semi-elective surgery, stop the eptifibatide 
infusion at an appropriate time to allow time for platelet function to return towards normal. 
 
Hepatic impairment 
Experience in patients with hepatic impairment is very limited. Administer with caution to patients 
with hepatic impairment in whom coagulation could be affected (see section 4.3, prothrombin time). It 
is contraindicated in patients with clinically significant hepatic impairment. 
 
Renal impairment 
In patients with moderate renal impairment (creatinine clearance ≥ 30 - < 50 ml/min), an intravenous 
bolus of 180 microgram/kg should be administered followed by a continuous infusion dose of 
1.0 microgram/kg/min for the duration of therapy. This recommendation is based on 
pharmacodynamic and pharmacokinetic data. The available clinical evidence cannot however confirm 
that this dose modification results in a preserved benefit (see section 5.1). Use in patients with more 
severe renal impairment is contraindicated (see section 4.3). 
 
Paediatric population 
It is not recommended for use in children and adolescents below 18 years of age, due to a lack of data 
on safety and efficacy. 
 
4.3 Contraindications 
 
Eptifibatide Accord must not be used to treat patients with: 
- hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
-  evidence of gastrointestinal bleeding, gross genitourinary bleeding or other active abnormal 
bleeding  within the previous 30 days of treatment 
-  history of stroke within 30 days or any history of haemorrhagic stroke 
- known history of intracranial disease (neoplasm, arteriovenous malformation, aneurysm) 
-  major surgery or severe trauma within past 6 weeks 
-  a history of bleeding diathesis 
-  thrombocytopenia (< 100,000 cells/mm3) 
-  prothrombin time > 1.2 times control, or International Normalized Ratio (INR) ≥  2.0 
-  severe hypertension (systolic blood pressure > 200 mm Hg or diastolic blood pressure 
 > 110 mm Hg on  antihypertensive therapy) 
-  severe renal impairment (creatinine clearance < 30 ml/min) or dependency on renal dialysis 
-  clinically significant hepatic impairment 
-  concomitant or planned administration of another parenteral glycoprotein (GP) IIb/IIIa inhibitor 
 
4.4 Special warnings and precautions for use 
 
Bleeding 
Eptifibatide Accord is an antithrombotic agent that acts by inhibition of platelet aggregation; therefore 
the patient must be observed carefully for indications of bleeding during treatment (see section 4.8). 
Women, the elderly, patients with low body weight or with moderate renal impairment (creatinine 



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clearance > 30 - < 50 ml/min) may have an increased risk of bleeding. Monitor these patients closely 
with regard to bleeding. 
 
An increased risk of bleeding may also be observed in patients who receive early administration of 
eptifibatide (e.g. upon diagnosis) compared to receiving it immediately prior to PCI, as seen in the 
Early ACS trial. Unlike the approved posology in the EU, all patients in this trial were administered a 
double bolus before the infusion (see section 5.1). 
 
Bleeding is most common at the arterial access site in patients undergoing percutaneous arterial 
procedures. All potential bleeding sites, (e.g., catheter insertion sites; arterial, venous, or needle 
puncture sites; cutdown sites; gastrointestinal and genitourinary tracts) must be observed carefully. 
Other potential bleeding sites such as central and peripheral nervous system and retroperitoneal sites, 
must be carefully considered too. 
 
Because Eptifibatide Accord inhibits platelet aggregation, caution must be employed when it is used 
with other medicinal products that affect haemostasis, including ticlopidine, clopidogrel, 
thrombolytics, oral anticoagulants, dextran solutions, adenosine, sulfinpyrazone, prostacyclin, non-
steroidal anti-inflammatory agents, or dypyridamole (see section 4.5). 
 
There is no experience with eptifibatide and low molecular weight heparins. 
 
There is limited therapeutic experience with eptifibatide in patients for whom thrombolytic therapy is 
generally indicated (e.g. acute transmural myocardial infarction with new pathological Q-waves or 
elevated ST-segments or left bundle branch block in the ECG). Consequently the use of Eptifibatide 
Accord is not recommended in these circumstances (see section 4.5). 
 
Eptifibatide Accord infusion should be stopped immediately if circumstances arise that necessitate 
thrombolytic therapy or if the patient must undergo an emergency CABG surgery or requires an 
intraortic balloon pump. 
 
If serious bleeding occurs that is not controllable with pressure, the Eptifibatide Accord infusion 
should be stopped immediately and any unfractionated heparin that is given concomitantly. 
 
Arterial procedures 
During treatment with eptifibatide there is a significant increase in bleeding rates, especially in the 
femoral artery area, where the catheter sheath is introduced. Take care to ensure that only the anterior 
wall of the femoral artery is punctured. Arterial sheaths may be removed when coagulation has 
returned to normal (e.g. when activated clotting time (ACT) is less than 180 seconds (usually 
2-6 hours after discontinuation of heparin). After removal of the introducer sheath, careful haemostasis 
must be ensured under close observation. 
 
Thrombocytopenia and Immunogencity related to GP IIb/IIIa inhibitors 
Eptifibatide Accord inhibits platelet aggregation, but does not appear to affect the viability of platelets. 
As demonstrated in clinical trials, the incidence of thrombocytopenia was low, and similar in patients 
treated with eptifibatide or placebo. Thrombocytopenia, including acute profound thrombocytopenia, 
has been observed with eptifibatide administration post-marketing (see section 4.8) 
 
The mechanism, whether immune- and/or non-immune-mediated, by which eptifibatide may induce 
thrombocytopenia is not fully understood. However, treatment with eptifibatide was associated with 
antibodies that recognise GPIIb/IIIa occupied by eptifibatide, suggesting an immune-mediated 
mechanism. Thrombocytopenia occurring after first exposure to a GPIIb/IIIa inhibitor may be 
explained by the fact that antibodies are naturally present in some normal individuals. 
 
Since either repeat exposure with any GP IIb/IIIa ligand-mimetic agent (like abciximab or eptifibatide) 
or first-time exposure to a GP IIb/IIIa inhibitor may be associated with immune-mediated 
thrombocytopenic responses, monitoring is required, i.e. platelet counts should be monitored prior to 



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treatment, within 6 hours of administration, and at least once daily thereafter while on therapy and 
immediately at clinical signs of unexpected bleeding tendency. 
 
If either a confirmed platelet decrease to < 100,000/mm3 or acute profound thrombocytopenia is 
observed, discontinuation of each treatment medication having known or suspected thrombocytopenic 
effects, including eptifibatide, heparin and clopidogrel, should be considered immediately. The 
decision to use platelet transfusions should be based upon clinical judgment on an individual basis. 
 
In patients with previous immune-mediated thrombocytopenia from other parenteral GP IIb/IIIa 
inhibitors, there are no data with the use of eptifibatide. Therefore, it is not recommended to 
administer eptifibatide in patients who have previously experienced immune mediated 
thrombocytopenia with GP IIb/IIIa inhibitors, including eptifibatide. 
 
Heparin administration 
Heparin administration is recommended unless a contraindication (such as a history of 
thrombocytopenia associated with use of heparin) is present. 
 
UA/NQMI: For a patient who weighs ≥  70 kg, it is recommended that a bolus dose of 5,000 units is 
given, followed by a constant intravenous infusion of 1,000 units/hr. If the patient weighs < 70 kg, a 
bolus dose of 60 units/kg is recommended, followed by an infusion of 12 units/kg/hr. The activated 
partial thromboplastin time (aPTT) must be monitored in order to maintain a value between 50 and 70 
seconds, above 70 seconds there may be an increased risk of bleeding. 
 
If PCI is to be performed in the setting of UA/NQMI, monitor the activated clotting time (ACT) to 
maintain a value between 300-350 seconds. Stop heparin administration if the ACT exceeds 
300 seconds; do not administer until the ACT falls below 300 seconds. 
 
Monitoring of laboratory values 
Before infusion of Eptifibatide Accord, the following laboratory tests are recommended to identify 
preexisting haemostatic abnormalities: prothrombin time (PT) and aPTT, serum creatinine, platelet 
count, haemoglobin and haematocrit levels. Haemoglobin, haematocrit, and platelet count are to be 
monitored as well within 6 hours after start of therapy and at least once daily thereafter while on 
therapy (or more often if there is evidence of a marked decrease). If the platelet count falls below 
100,000/mm3, further platelet counts are required to rule out pseudothrombocytopenia. Discontinue 
unfractionated heparin. In patients undergoing PCI, measure the ACT also. 
 
Sodium 
Eptifibatide Accord 0.75 mg/ml solution for infusion contains 77.4 mg (3.37 mmol) of sodium per 
maximum daily dose. This should be taken into consideration by patients on a controlled sodium diet. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Warfarin and dipyridamole 
Eptifibatide did not appear to increase the risk of major and minor bleeding associated with 
concomitant use of warfarin and dipyridamole. Eptifibatide -treated patients who had a prothrombin 
time (PT) > 14.5 seconds and received warfarin concomitantly did not appear to be at an increased risk 
of bleeding. 
 
Eptifibatide and thrombolytic agents 
Data are limited on the use of eptifibatide in patients receiving thrombolytic agents. There was no 
consistent evidence that eptifibatide increased the risk of major or minor bleeding associated with 
tissue plasminogen activator in either a PCI or an acute myocardial infarction study. Eptifibatide 
appeared to increase the risk of bleeding when administered with streptokinase in an acute myocardial 
infarction study. The combination of reduced dose tenecteplase and eptifibatide compared to placebo 
and eptifibatide significantly increased the risk of both major and minor bleeding when administered 
concomitantly in an acute ST-elevation myocardial infarction study. 
 



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In an acute myocardial infarction study involving 181 patients, eptifibatide (in regimens up to a bolus 
injection of 180 microgram/kg, followed by an infusion up to 2 microgram/kg/min for up to 72 hours) 
was administered concomitantly with streptokinase (1.5 million units over 60 minutes). At the highest 
infusion rates (1.3 microgram/kg/min and 2.0 microgram/kg/min) studied, eptifibatide was associated 
with an increased incidence of bleeding and transfusions compared to the incidence seen when 
streptokinase was given alone. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no adequate data from the use of eptifibatide in pregnant women. 
 
Animal studies are insufficient with respect to effects on pregnancy, embryonal/foetal development, 
parturition or postnatal development (see section 5.3). The potential risk for humans is unknown.  
Eptifibatide Accord should not be used during pregnancy unless clearly necessary. 
Breast-feeding 
It is not known whether eptifibatide is excreted in human milk. Interruption of breast-feeding during 
the treatment period is recommended. 
 
4.7 Effects on ability to drive and use machines 
 
Not relevant, as Eptifibatide Accord is intended for use only in hospitalised patients. 
 
4.8 Undesirable effects 
 
The majority of adverse reactions experienced by patients treated with eptifibatide were generally 
related to bleeding or to cardiovascular events that occur frequently in this patient population. 
 
Clinical Trials 
The data sources used to determine adverse reaction frequency descriptors included two phase III 
clinical studies (PURSUIT and ESPRIT). These trials are briefly described below. 
 
PURSUIT: This was a randomized, double-blind evaluation of the efficacy and safety of eptifibatide 
versus placebo for reducing mortality and myocardial (re)infarction in patients with unstable angina or 
non-Q-wave myocardial infarction. 
 
ESPRIT: This was a double-blind, multicentre, randomized, parallel-group, placebo-controlled trial 
evaluating the safety and efficacy of eptifibatide therapy in patients scheduled to undergo non-
emergent percutaneous coronary intervention (PCI) with stent implantation. 
 
In PURSUIT, bleeding and non-bleeding events were collected from hospital discharge to the 30 day 
visit. In ESPRIT, bleeding events were reported at 48 hours, and non-bleeding events were reported at 
30 days. While Thrombolysis in Myocardial Infarction TIMI bleeding criteria were used to categorize 
the incidence of major and minor bleeding in both the PURSUIT and the ESPRIT trials, PURSUIT 
data was collected within 30 days while ESPRIT data was limited to events within 48 hours or 
discharge, whichever came first. 
 
The undesirable effects are listed by body system and frequency. Frequencies are defined as very 
common (≥ 1/10); common (≥ 1/100 to<  1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to 
< 1/1000); very rare (< 1/10,000); not known (cannot be estimated from available data). These are 
absolute reporting frequencies without taking into account placebo rates. For a particular adverse 
reaction, if data was available from both PURSUIT and ESPRIT, then the highest reported incidence 
was used to assign adverse reaction frequency. 
Note that causality has not been determined for all adverse reactions. 
 



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Blood and Lymphatic System Disorder 
Very common Bleeding (major and minor bleeding including femoral artery access, CABG-

related, gastrointestinal, genitourinary, retroperitoneal, intracranial, haematemesis, 
haematuria, oral/oropharyngeal, haemoglobin/haematocrit decreased and other). 

Uncommon Thrombocytopenia. 
Nervous System disorders 
Uncommon Cerebral ischaemia. 
Cardiac Disorders 
Common Cardiac arrest, ventricular fibrillation, ventricular tachycardia, congestive heart 

failure, atrioventricular block, atrial fibrillation. 
Vascular Disorders 
Common Shock, hypotension, phlebitis. 

 
Cardiac arrest, congestive heart failure, atrial fibrillation, hypotension, and shock, which are 
commonly reported events from the PURSUIT trial, were events related to the underlying disease. 
 
Administration of eptifibatide is associated with an increase in major and minor bleeding as classified 
by the criteria of the TIMI study group. At the recommended therapeutic dose, as administered in the 
PURSUIT trial involving nearly 11,000 patients, bleeding was the most common complication 
encountered during eptifibatide therapy. The most common bleeding complications were associated 
with cardiac invasive procedures (coronary artery bypass grafting (CABG)-related or at femoral artery 
access site). 
 
Minor bleeding was defined in the PURSUIT trial as spontaneous gross haematuria, spontaneous 
haematemesis, observed blood loss with a haemoglobin decrease of more than 3 g/dl, or a 
haemoglobin decrease of more than 4 g/dl in the absence of an observed bleeding site. During 
treatment with eptifibatide in this study, minor bleeding was a very common complication (> 1/10, or 
13.1 % for eptifibatide versus 7.6 % for placebo). Bleeding events were more frequent in patients 
receiving concurrent heparin while undergoing PCI, when ACT exceeded 350 seconds (see section 
4.4, heparin use). 
 
Major bleeding was defined in the PURSUIT trial as either an intracranial haemorrhage or a decrease 
in haemoglobin concentrations of more than 5 g/dl. Major bleeding was also very common and 
reported more frequently with eptifibatide than with placebo in the PURSUIT study (> 1/10 or 10.8 % 
versus 9.3 %), but it was infrequent in the vast majority of patients who did not undergo CABG within 
30 days of inclusion in the study. In patients undergoing CABG, the incidence of bleeding was not 
increased by eptifibatide compared to the patients treated with placebo. In the subgroup of patients 
undergoing PCI, major bleeding was observed commonly, in 9.7 % of eptifibatide -treated patients vs. 
4.6 % of placebo-treated patients. 
 
The incidence of severe or life threatening bleeding events with eptifibatide was 1.9 % compared to 
1.1 % with placebo. The need for blood transfusions was increased modestly by eptifibatide treatment 
(11.8 % versus 9.3 % for placebo). 
 
Changes during eptifibatide treatment result from its known pharmacological action, i.e., inhibition of 
platelet aggregation. Thus, changes in laboratory parameters associated with bleeding (e.g. bleeding 
time) are common and expected. No apparent differences were observed between patients treated with 
eptifibatide or with placebo in values for liver function (SGOT/AST, SGPT/ALT, bilirubin, alkaline 
phosphatase) or renal function (serum creatinine, blood urea nitrogen). 
 
Post-marketing experience 
 
Blood and lymphatic system disorders 
Very rare Fatal bleeding (the majority involved central and peripheral nervous system 

disorders: cerebral or intracranial haemorrhages); pulmonary haemorrhage, 
acute profound thrombocytopenia, haematoma. 



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Immune system disorders 
Very rare Anaphylactic reactions. 
Skin and subcutaneous tissue disorders 
Very rare Rash, application site disorders such as urticaria. 
 
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 national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
The experience in humans with overdose of eptifibatide is extremely limited. There was no indication 
of severe adverse reactions associated with administration of accidental large bolus doses, rapid 
infusion reported as overdose or large cumulative doses. In the PURSUIT trial, there were 9 patients 
who received bolus and/or infusion doses more than double the recommended dose, or who were 
identified by the investigator as having received an overdose. There was no excessive bleeding in any 
of these patients, although one patient undergoing CABG surgery was reported as having had a 
moderate bleed. Specifically, no patients experienced an intracranial bleed. 
 
Potentially, an overdose of eptifibatide could result in bleeding. Because of its short half-life and rapid 
clearance, the activity of eptifibatide may be halted readily by discontinuing the infusion. Thus, 
although eptifibatide can be dialysed, the need for dialysis is unlikely. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antithrombotic agent (platelet aggregation inhibitors excl. heparin), ATC 
code: B01AC16 
 
Mechanism of action 
 
Eptifibatide, a synthetic cyclic heptapeptide containing six amino acids, including one cysteine amide 
and one mercaptopropionyl (desamino cysteinyl) residue, is an inhibitor of platelet aggregation and 
belongs to the class of RGD (arginine-glycine-aspartate)-mimetics. 
 
Eptifibatide reversibly inhibits platelet aggregation by preventing the binding of fibrinogen, von 
Willebrand factor and other adhesive ligands to the glycoprotein (GP) IIb/IIIa receptors. 
 
Pharmacodynamic effects 
 
Eptifibatide inhibits platelet aggregation in a dose- and concentration-dependent manner as 
demonstrated by ex vivo platelet aggregation using adenosine diphosphate (ADP) and other agonists to 
induce platelet aggregation. The effect of eptifibatide is observed immediately after administration of a 
180 microgram/kg intravenous bolus. When followed by a 2.0 microgram/kg/min continuous infusion, 
this regimen produces a > 80 % inhibition of ADP-induced ex vivo platelet aggregation, at physiologic 
calcium concentrations, in more than 80 % of patients. 
 
Platelet inhibition was readily reversed, with a return of platelet function towards baseline (> 50 % 
platelet aggregation) 4 hours after stopping a continuous infusion of 2.0 microgram/kg/min. 
Measurements of ADP-induced ex vivo platelet aggregation at physiologic calcium concentrations 
(Dphenylalanyl-L-prolyl-L-arginine chloromethyl ketone anticoagulant) in patients presenting with 
unstable angina and Non Q-Wave Myocardial Infarction showed a concentration-dependent inhibition 

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with an IC50 (50 % inhibitory concentration) of approximately 550 ng/ml and an IC80 (80 % inhibitory 
concentration) of approximately 1,100 ng/ml. 
 
There is limited data with regards to platelet inhibition in patients with renal impairment. In patients 
with moderate renal impairment, (creatinine clearance 30 - 50 ml/min) 100 % inhibition was achieved 
at 24 hours following administration of 2 microgram/kg/min. In patients with severe renal impairment 
(creatinine clearance < 30 ml/min) administered 1microgram/kg/min , 80 % inhibition was achieved in 
more than 80 % of patients at 24 hours. 
 
Clinical efficacy and safety 
 
PURSUIT trial 
The pivotal clinical trial for Unstable Angina (UA)/Non-Q Wave Myocardial Infarction (NQMI) was 
PURSUIT. This study was a 726-center, 27-country, double-blind, randomised, placebo-controlled 
study in 10,948 patients presenting with UA or NQMI. Patients could be enrolled only if they had 
experienced cardiac ischemia at rest (≥ 10 minutes) within the previous 24 hours and had: 

• either ST-segment changes: ST depression > 0.5 mm of less than 30 minutes or persistent ST 
elevation > 0.5 mm not requiring reperfusion therapy or thrombolytic agents, T-wave 
inversion (> 1 mm), 

• or increased CK-MB. 
 
Patients were randomised to either placebo, eptifibatide 180 microgram/kg bolus followed by a 
2.0 microgram/kg/min infusion (180/2.0), or eptifibatide 180 microgram/kg bolus followed by a 
1.3 microgram/kg/min infusion (180/1.3). 
 
The infusion was continued until hospital discharge, until the time of coronary artery bypass grafting 
(CABG) or for up to 72 hours, whichever occurred first. If PCI was performed, the eptifibatide 
infusion was continued for 24 hours after the procedure, allowing for a duration of infusion up to 96 
hours. 
 
The 180/1.3 arm was stopped after an interim analysis, as prespecified in the protocol, when the two 
active-treatment arms appeared to have a similar incidence of bleeding. 
 
Patients were managed according to the usual standards of the investigational site; frequencies of 
angiography, PCI and CABG therefore differed widely from site to site and from country to country. 
Of the patients in PURSUIT, 13 % were managed with PCI during eptifibatide infusion, of whom 
approximately 50 % received intracoronary stents; 87 % were managed medically (without PCI during 
eptifibatide infusion). 
 
The vast majority of patients received acetylsalicylic acid (75-325 mg once daily). 
 
Unfractionated heparin was administered intravenously or subcutaneously at the physician’s 
discretion, most commonly as an intravenous bolus of 5,000 U followed by a continuous infusion of 
1,000 U/h. A target aPTT of 50-70 seconds was recommended. A total of 1,250 patients underwent 
PCI within 72 hours after randomisation, in which case they received intravenous unfractionated 
heparin to maintain an activated clotting time (ACT) of 300-350 seconds. 
 
The primary endpoint of the study was the occurrence of death from any cause or new myocardial 
infarction (MI) (evaluated by a blinded Clinical Events Committee) within 30 days of randomisation. 
The component MI could be defined as asymptomatic with enzymatic elevation of CK-MB or new Q 
wave. 
 
Compared to placebo, eptifibatide administered as 180/2.0 significantly reduced the incidence of the 
primary endpoint events (table 1): this represents around 15 events avoided for 1,000 patients treated: 
 
 
 



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Table 1: Incidence of Death/CEC-Assessed MI («Treated as Randomised» Population) 
 
Time Placebo Eptifibatide p-Value 
30 days 743/4,697 

(15.8 %) 
667/4,680 
(14.3 %) 

0.034a 

a: Pearson’s chi-square test of difference between placebo and eptifibatide. 
 
Results on the primary endpoint were principally attributed to the occurrence of myocardial infarction. 
The reduction in the incidence of endpoint events in patients receiving eptifibatide appeared early 
during treatment (within the first 72-96 hours) and this reduction was maintained through 6 months, 
without any significant effect on mortality. 
 
Patients most likely to benefit from eptifibatide treatment are those at high risk of developing 
myocardial infarction within the first 3-4 days after onset of acute angina. 
 
According to epidemiological findings, a higher incidence of cardiovascular events has been 
associated with certain indicators, for instance: 
-  age 
-  elevated heart rate or blood pressure 
-  persistent or recurrent ischemic cardiac pain 
-  marked ECG changes (in particular ST-segment abnormalities) 
-  raised cardiac enzymes or markers (e.g. CK-MB, troponins) and 
-  heart failure 
 
PURSUIT was conducted at a time when the standard of care of managing acute coronary syndromes 
was different from that of present times in terms of thienopyridine use and the routine use of 
intracoronary stents. 
 
ESPRIT trial 
ESPRIT (Enhanced Suppression of the Platelet IIb/IIIa Receptor with eptifibatide Therapy) was a 
double-blind, randomised, placebo-controlled trial (n= 2,064) for nonurgent PCI with intracoronary 
stenting. 
 
All patients received routine standard of care and were randomised to either placebo or eptifibatide (2 
bolus doses of 180 microgram/kg and a continuous infusion until discharge from hospital or a 
maximum of 18-24 hours). 
 
The first bolus and the infusion were started simultaneously, immediately before the PCI procedure 
and were followed by a second bolus 10 minutes after the first. The rate of infusion was 2.0 
microgram/kg/min for patients with serum creatinine ≤ 175 micromols/l or 1.0 microgram/kg/min for 
serum creatinine > 175 up to 350 micromols/l. 
 
In the eptifibatide arm of the trial, virtually all patients received aspirin (99.7 %), and 98.1 % received 
a thienopyridine, (clopidogrel in 95.4 % and ticlopidine in 2.7 %). On the day of PCI, prior to 
catheterization, 53.2 % received a thienopyridine (clopidogrel 52.7 %; ticlopidine 0.5 %) – mostly as a 
loading dose (300 mg or more). The placebo arm was comparable (aspirin 99.7 %, clopidogrel 95.9 %, 
ticlopidin 2.6 %). 
 
The ESPRIT trial used a simplified regimen of heparin during PCI that consisted of an initial bolus of 
60 units/kg, with a target ACT of 200 - 300 seconds. The primary endpoint of the trial was death (D), 
MI, urgent target vessel revascularisation (UTVR), and acute antithrombotic rescue with GP IIb/IIIa 
inhibitor therapy (RT) within 48 hours of randomisation. 
 
MI was identified per the CK-MB core laboratory criteria. For this diagnosis, within 24 hours after the 
index PCI procedure, there had to be at least two CK-MB values ≥  3 x the upper limit of normal; thus, 
validation by the CEC was not required. MI could also be reported following CEC adjudication of an 
investigator report. 



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The primary endpoint analysis [quadruple composite of death, MI, urgent target vessel 
revascularisation (UTVR) and thrombolytic bail-out (TBO) at 48 hours] showed a 37 % relative and 
3.9 % absolute reduction in the eptifibatide group (6.6 % events versus 10.5 %, p=  0.0015). Results 
on the primary endpoint were mainly attributed to the reduction of enzymatic MI occurrence, 
identified as the occurrence of early elevation of cardiac enzymes after PCI (80 out of 92 MIs in the 
placebo group vs. 47 out of 56 MIs in the eptifibatide group). The clinical relevance of such enzymatic 
MIs is still controversial. 
 
Similar results were also obtained for the 2 secondary endpoints assessed at 30 days: a triple 
composite of death, MI and UTVR, and the more robust combination of death and MI. 
 
The reduction in the incidence of endpoint events in patients receiving eptifibatide appeared early 
during treatment. There was no increased benefit thereafter, up to 1 year. 
 
Prolongation of bleeding time 
Administration of eptifibatide by intravenous bolus and infusion causes up to a 5-fold increase in 
bleeding time. This increase is readily reversible upon discontinuation of the infusion with bleeding 
times returning towards baseline in approximately 6 (2-8) hours. When administered alone, 
eptifibatide has no measurable effect on prothrombin time (PT) or activated partial thromboplastin 
time (aPTT). 
 
EARLY-ACS trial 
EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Non-ST-segment Elevation Acute Coronary 
Syndrome) was a study of early routine eptifibatide versus placebo (with delayed provisional use of 
eptifibatide in the catheterization laboratory) used in combination with antithrombotic therapies (ASA, 
UFH, bivalirudin, fondaparinux or low molecular weight heparin), in subjects with high-risk NSTE 
ACS. Patients were to undergo an invasive strategy for further management after receiving study drug 
for 12 to 96 hours. Patients could be medically managed, proceed to coronary artery bypass graft 
(CABG), or undergo percutaneous coronary intervention (PCI). Unlike the approved posology in the 
EU, the study used a double bolus of study drug (separated by 10 minutes) before the infusion. 
 
Early routine eptifibatide in this high-risk NSTE-ACS optimally-treated population who were 
managed with an invasive strategy did not result in a statistically significant reduction in the 
composite primary endpoint of rate of death, MI, RI-UR, and TBO within 96 hours compared with a 
regimen of delayed provisional eptifibatide (9.3 % in early eptifibatide patients vs. 10.0 % in patients 
assigned to delayed provisional eptifibatide; odds ratio=0.920; 95 % CI=0.802-1.055; p=0.234). 
GUSTO severe/life threatening bleeding was uncommon and comparable in both treatment groups 
(0.8 %). GUSTO moderate or severe/life threatening bleeding occurred significantly more often with 
early routine eptifibatide (7.4 % vs. 5.0 % in delayed provisional eptifibatide group; p <0.001). Similar 
differences were noted for TIMI major haemorrhage (118 [2.5 %] in early routine use vs. 83 [1.8 %] in 
delayed provisional use; p=0.016). 
 
No statistically significant benefit of early routine eptifibatide strategy was demonstrated in the 
subgroup of patients who were managed medically or during the medical management periods prior to 
PCI or CABG. 
 
In a post hoc analysis of the EARLY ACS trial the risk benefit of dose reduction in patients with 
moderate renal impairment is inconclusive. The primary endpoint event rate was 11.9 % in patients 
who received a reduced dose (1microgram/kg/min) vs 11.2 % in patients who received the standard 
dose (2 microgram/kg/min) when eptifibatide was administered in the early routine fashion (p=0.81). 
With delayed provisional eptifibatide administration, the event rates were 10 % vs 11.5 % in patients 
who received reduced dose and standard dose respectively (p=0.61). TIMI major bleeding occurred in 
2.7 % of patients who received a reduced dose (1microgram/kg/min) vs 4.2 % of patients who 
received the standard dose (2 microgram/kg/min) when eptifibatide was administered in the early 
routine fashion (p=0.36). With delayed provisional eptifibatide administration, the TIMI major events 



12 

were 1.4 % vs 2.0 % in patients who received reduced dose and standard dose respectively 
(p=0.54).There were no notable differences observed with GUSTO severe bleeding rates. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
The pharmacokinetics of eptifibatide are linear and dose proportional for bolus doses ranging from 90 
to 250 microgram/kg and infusion rates from 0.5 to 3.0 microgram/kg/min.  
 
Distrobution 
For a 2.0 microgram/kg/min infusion, mean steady-state plasma eptifibatide concentrations range from 
1.5 to 2.2 microgram/ml in patients with coronary artery disease. These plasma concentrations are 
achieved rapidly when the infusion is preceded by a 180microgram/kg bolus.  
Biotransformation 
The extent of eptifibatide binding to human plasma protein is about 25 %. In the same population, 
plasma elimination half-life is approximately 2.5 hours, plasma clearance 55 to 80 ml/kg/hr and 
volume of distribution of approximately 185 to 260 ml/kg. 
 
Elimination 
In healthy subjects, renal excretion accounted for approximately 50 % of total body clearance; 
approximately 50 % of the amount cleared is excreted unchanged. In patients with moderate to severe 
renal insufficiency (creatinine clearance < 50 ml/min), the clearance of eptifibatide is reduced by 
approximately 50 % and steady-state plasma levels are approximately doubled. 
 
No formal pharmacokinetic interaction studies have been conducted. However, in a population 
pharmacokinetic study there was no evidence of a pharmacokinetic interaction between eptifibatide 
and the following concomitant medicinal products: amlodipine, atenolol, atropine, captopril, cefazolin, 
diazepam, digoxin, diltiazem, diphenhydramine, enalapril, fentanyl, furosemide, heparin, lidocaine, 
lisinopril, metoprolol, midazolam, morphine, nitrates, nifedipine, and warfarin. 
 
5.3 Preclinical safety data 
 
Toxicology studies conducted with eptifibatide include single and repeated dose studies in the rat, 
rabbit and monkey, reproduction studies in the rat and rabbit, in vitro and in vivo genetic toxicity 
studies, and irritation, hypersensitivity and antigenicity studies. No unexpected toxic effects for an 
agent with this pharmacologic profile were observed and findings were predictive of clinical 
experience, with bleeding effects being the principal adverse event. No genotoxic effects were 
observed with eptifibatide. 
 
Teratology studies have been performed by continuous intravenous infusion of eptifibatide in pregnant 
rats at total daily doses of up to 72 mg/kg/day (about 4 times the recommended maximum daily human 
dose on a body surface area basis) and in pregnant rabbits at total daily doses of up to 36 mg/kg/day 
(about 4 times the recommended maximum daily human dose on a body surface area basis). These 
studies revealed no evidence of impaired fertility or harm to the foetus due to eptifibatide. 
 
Reproduction studies in animal species where eptifibatide shows a similar pharmacologic activity as in 
humans are not available. Consequently these studies are not suitable to evaluate the toxicity of 
eptifibatide on reproductive function (see section 4.6). 
 
The carcinogenic potential of eptifibatide has not been evaluated in long-term studies. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Citric acid monohydrate 



13 

Sodium hydroxide 
Water for injections 
 
6.2 Incompatibilities 
 
Eptifibatide Accord is not compatible with furosemide. 
 
In the absence of compatibility studies, Eptifibatide Accord must not be mixed with other medicinal 
products except those mentioned in 6.6. 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). 
Store in the original package in order to protect from light. 
 
6.5 Nature and contents of container  
 
One 100 ml Type I glass vial, closed with a butyl rubber stopper and sealed with a flip-off aluminium 
seal. 
 
6.6 Special precautions for disposal and other handling 
 
Physical and chemical compatibility testing indicate that Eptifibatide Accord may be administered 
through an intravenous line with atropine sulfate, dobutamine, heparin, lidocaine, meperidine, 
metoprolol, midazolam, morphine, nitroglycerin, tissue plasminogen activator, or verapamil. 
Eptifibatide Accord is chemically and physically compatible with 0.9 % sodium chloride solution for 
infusion and with dextrose 5 % in Normosol R with or without potassium chloride up to 92 hours 
when stored at 20-25°C. Please refer to the Normosol R Summary of Product Characteristics for 
details on its composition. 
 
Before using, inspect the vial contents. Do not use if particulate matter or discolouration is present. 
Protection of Eptifibatide Accord solution from light is not necessary during administration. 
 
Discard any unused medicinal product after opening. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
8. MARKETING AUTHORISATION NUMBER  
 
EU/1/15/1065/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 11th January 2016 



14 

 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency  http://www.ema.europa.eu 

http://www.ema.europa.eu/


15 

1. NAME OF THE MEDICINAL PRODUCT 
 
Eptifibatide Accord 2 mg/ml solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of solution for injection contains 2 mg of eptifibatide. 
 
One vial of 10 ml of solution for injection contains 20 mg of eptifibatide. 
 
Excipient with known effect: 
2 mg/ml :   3.45 mg/ml (0.150 mmol/ml) sodium 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection. 
 
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Eptifibatide Accord is intended for use with acetylsalicylic acid and unfractionated heparin. 
 
Eptifibatide Accord is indicated for the prevention of early myocardial infarction in adults presenting 
with unstable angina or non-Q-wave myocardial infarction, with the last episode of chest pain 
occurring within 24 hours and with electrocardiogram (ECG) changes and/or elevated cardiac 
enzymes. 
 
Patients most likely to benefit from Eptifibatide Accord treatment are those at high risk of developing 
myocardial infarction within the first 3-4 days after onset of acute angina symptoms including for 
instance those that are likely to undergo an early PTCA (Percutaneous Transluminal Coronary 
Angioplasty) (see section 5.1). 
 
4.2 Posology and method of administration 
 
This product is for hospital use only. It should be administered by specialist physicians experienced in 
the management of acute coronary syndromes. 
 
Eptifibatide Accord solution for injection must be used in conjunction with Eptifibatide Accord 
solution for infusion. 
 
Concurrent administration of heparin is recommended unless this is contraindicated for reasons such 
as a history of thrombocytopenia associated with use of heparin (see ‘Heparin administration’, section 
4.4). Eptifibatide Accord is also intended for concurrent use with acetylsalicylic acid, as it is part of 
standard management of patients with acute coronary syndromes, unless its use is contraindicated. 
 
Posology 
 



16 

Adults (≥ 18 years of age) presenting with unstable angina (UA) or non-Q-wave myocardial infarction 
(NQMI) 
The recommended dosage is an intravenous bolus of 180 microgram/kg administered as soon as 
possible following diagnosis, followed by a continuous infusion of 2 microgram/kg/min for up to 72 
hours, until initiation of coronary artery bypass graft (CABG) surgery, or until discharge from the 
hospital (whichever occurs first). If Percutaneous Coronary Intervention (PCI) is performed during 
eptifibatide therapy, continue the infusion for 20-24 hours post-PCI for an overall maximum duration 
of therapy of 96 hours. 
 
Emergency or semi-elective surgery 
If the patient requires emergency or urgent cardiac surgery during the course of eptifibatide therapy, 
terminate the infusion immediately. If the patient requires semi-elective surgery, stop the eptifibatide 
infusion at an appropriate time to allow time for platelet function to return towards normal. 
 
Hepatic impairment 
Experience in patients with hepatic impairment is very limited. Administer with caution to patients 
with hepatic impairment in whom coagulation could be affected (see section 4.3, prothrombin time). It 
is contraindicated in patients with clinically significant hepatic impairment. 
 
Renal impairment 
In patients with moderate renal impairment (creatinine clearance ≥ 30 - < 50 ml/min), an intravenous 
bolus of 180 microgram/kg should be administered followed by a continuous infusion dose of 
1.0 microgram/kg/min for the duration of therapy. This recommendation is based on 
pharmacodynamic and pharmacokinetic data. The available clinical evidence cannot however confirm 
that this dose modification results in a preserved benefit (see section 5.1). Use in patients with more 
severe renal impairment is contraindicated (see section 4.3). 
 
Paediatric population 
It is not recommended for use in children and adolescents below 18 years of age, due to a lack of data 
on safety and efficacy. 
 
4.3 Contraindications 
 
Eptifibatide Accord must not be used to treat patients with: 
- hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
-  evidence of gastrointestinal bleeding, gross genitourinary bleeding or other active abnormal 
bleeding  within the previous 30 days of treatment 
-  history of stroke within 30 days or any history of haemorrhagic stroke 
- known history of intracranial disease (neoplasm, arteriovenous malformation, aneurysm) 
-  major surgery or severe trauma within past 6 weeks 
-  a history of bleeding diathesis 
-  thrombocytopenia (< 100,000 cells/mm3) 
-  prothrombin time > 1.2 times control, or International Normalized Ratio (INR) ≥ 2.0 
-  severe hypertension (systolic blood pressure > 200 mm Hg or diastolic blood pressure > 110 mm 
Hg on  antihypertensive therapy) 
-  severe renal impairment (creatinine clearance < 30 ml/min) or dependency on renal dialysis 
-  clinically significant hepatic impairment 
-  concomitant or planned administration of another parenteral glycoprotein (GP) IIb/IIIa inhibitor 
 
4.4 Special warnings and precautions for use 
 
Bleeding 
Eptifibatide Accord is an antithrombotic agent that acts by inhibition of platelet aggregation; therefore 
the patient must be observed carefully for indications of bleeding during treatment (see section 4.8). 
Women, the elderly, patients with low body weight or with moderate renal impairment (creatinine 



17 

clearance > 30 - < 50 ml/min) may have an increased risk of bleeding. Monitor these patients closely 
with regard to bleeding. 
 
An increased risk of bleeding may also be observed in patients who receive early administration of 
eptifibatide (e.g. upon diagnosis) compared to receiving it immediately prior to PCI, as seen in the 
Early ACS trial. Unlike the approved posology in the EU, all patients in this trial were administered a 
double bolus before the infusion (see section 5.1). 
 
Bleeding is most common at the arterial access site in patients undergoing percutaneous arterial 
procedures. All potential bleeding sites, (e.g., catheter insertion sites; arterial, venous, or needle 
puncture sites; cutdown sites; gastrointestinal and genitourinary tracts) must be observed carefully. 
Other potential bleeding sites such as central and peripheral nervous system and retroperitoneal sites, 
must be carefully considered too. 
 
Because Eptifibatide Accord inhibits platelet aggregation, caution must be employed when it is used 
with other medicinal products that affect haemostasis, including ticlopidine, clopidogrel, 
thrombolytics, oral anticoagulants, dextran solutions, adenosine, sulfinpyrazone, prostacyclin, non-
steroidal anti-inflammatory agents, or dypyridamole (see section 4.5). 
 
There is no experience with eptifibatide and low molecular weight heparins. 
 
There is limited therapeutic experience with eptifibatide in patients for whom thrombolytic therapy is 
generally indicated (e.g. acute transmural myocardial infarction with new pathological Q-waves or 
elevated ST-segments or left bundle branch block in the ECG). Consequently the use of Eptifibatide 
Accord is not recommended in these circumstances (see section 4.5). 
 
Eptifibatide Accord infusion should be stopped immediately if circumstances arise that necessitate 
thrombolytic therapy or if the patient must undergo an emergency CABG surgery or requires an 
intraortic balloon pump. 
 
If serious bleeding occurs that is not controllable with pressure, the Eptifibatide Accord infusion 
should be stopped immediately and any unfractionated heparin that is given concomitantly. 
 
Arterial procedures 
During treatment with eptifibatide there is a significant increase in bleeding rates, especially in the 
femoral artery area, where the catheter sheath is introduced. Take care to ensure that only the anterior 
wall of the femoral artery is punctured. Arterial sheaths may be removed when coagulation has 
returned to normal (e.g. when activated clotting time (ACT) is less than 180 seconds (usually 
2-6 hours after discontinuation of heparin). After removal of the introducer sheath, careful haemostasis 
must be ensured under close observation. 
 
Thrombocytopenia and Immunogencity related to GP IIb/IIIa inhibitors 
Eptifibatide Accord inhibits platelet aggregation, but does not appear to affect the viability of platelets. 
As demonstrated in clinical trials, the incidence of thrombocytopenia was low, and similar in patients 
treated with eptifibatide or placebo. Thrombocytopenia, including acute profound thrombocytopenia, 
has been observed with eptifibatide administration post-marketing (see section 4.8) 
 
The mechanism, whether immune- and/or non-immune-mediated, by which eptifibatide may induce 
thrombocytopenia is not fully understood. However, treatment with eptifibatide was associated with 
antibodies that recognise GPIIb/IIIa occupied by eptifibatide, suggesting an immune-mediated 
mechanism. Thrombocytopenia occurring after first exposure to a GPIIb/IIIa inhibitor may be 
explained by the fact that antibodies are naturally present in some normal individuals. 
 
Since either repeat exposure with any GP IIb/IIIa ligand-mimetic agent (like abciximab or eptifibatide) 
or first-time exposure to a GP IIb/IIIa inhibitor may be associated with immune-mediated 
thrombocytopenic responses, monitoring is required, i.e. platelet counts should be monitored prior to 



18 

treatment, within 6 hours of administration, and at least once daily thereafter while on therapy and 
immediately at clinical signs of unexpected bleeding tendency. 
 
If either a confirmed platelet decrease to < 100,000/mm3 or acute profound thrombocytopenia is 
observed, discontinuation of each treatment medication having known or suspected thrombocytopenic 
effects, including eptifibatide, heparin and clopidogrel, should be considered immediately. The 
decision to use platelet transfusions should be based upon clinical judgment on an individual basis. 
 
In patients with previous immune-mediated thrombocytopenia from other parenteral GP IIb/IIIa 
inhibitors, there are no data with the use of eptifibatide. Therefore, it is not recommended to 
administer eptifibatide in patients who have previously experienced immune mediated 
thrombocytopenia with GP IIb/IIIa inhibitors, including eptifibatide. 
 
Heparin administration 
Heparin administration is recommended unless a contraindication (such as a history of 
thrombocytopenia associated with use of heparin) is present. 
 
UA/NQMI: For a patient who weighs ≥  70 kg, it is recommended that a bolus dose of 5,000 units is 
given, followed by a constant intravenous infusion of 1,000 units/hr. If the patient weighs < 70 kg, a 
bolus dose of 60 units/kg is recommended, followed by an infusion of 12 units/kg/hr. The activated 
partial thromboplastin time (aPTT) must be monitored in order to maintain a value between 50 and 70 
seconds, above 70 seconds there may be an increased risk of bleeding. 
 
If PCI is to be performed in the setting of UA/NQMI, monitor the activated clotting time (ACT) to 
maintain a value between 300-350 seconds. Stop heparin administration if the ACT exceeds 
300 seconds; do not administer until the ACT falls below 300 seconds. 
 
Monitoring of laboratory values 
Before infusion of Eptifibatide Accord, the following laboratory tests are recommended to identify 
preexisting haemostatic abnormalities: prothrombin time (PT) and aPTT, serum creatinine, platelet 
count, haemoglobin and haematocrit levels. Haemoglobin, haematocrit, and platelet count are to be 
monitored as well within 6 hours after start of therapy and at least once daily thereafter while on 
therapy (or more often if there is evidence of a marked decrease). If the platelet count falls below 
100,000/mm3, further platelet counts are required to rule out pseudothrombocytopenia. Discontinue 
unfractionated heparin. In patients undergoing PCI, measure the ACT also. 
 
Sodium 
Eptifibatide Accord 2 mg/ml solution for injection contains 57.96 mg (2.52 mmol) of sodium per 
maximum daily dose. This should be taken into consideration by patients on a controlled sodium diet. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Warfarin and dipyridamole 
Eptifibatide did not appear to increase the risk of major and minor bleeding associated with 
concomitant use of warfarin and dipyridamole. Eptifibatide -treated patients who had a prothrombin 
time (PT) > 14.5 seconds and received warfarin concomitantly did not appear to be at an increased risk 
of bleeding. 
 
Eptifibatide and thrombolytic agents 
Data are limited on the use of eptifibatide in patients receiving thrombolytic agents. There was no 
consistent evidence that eptifibatide increased the risk of major or minor bleeding associated with 
tissue plasminogen activator in either a PCI or an acute myocardial infarction study. Eptifibatide 
appeared to increase the risk of bleeding when administered with streptokinase in an acute myocardial 
infarction study. The combination of reduced dose tenecteplase and eptifibatide compared to placebo 
and eptifibatide significantly increased the risk of both major and minor bleeding when administered 
concomitantly in an acute ST-elevation myocardial infarction study. 
 



19 

In an acute myocardial infarction study involving 181 patients, eptifibatide (in regimens up to a bolus 
injection of 180 microgram/kg, followed by an infusion up to 2 microgram/kg/min for up to 72 hours) 
was administered concomitantly with streptokinase (1.5 million units over 60 minutes). At the highest 
infusion rates (1.3 microgram/kg/min and 2.0 microgram/kg/min) studied, eptifibatide was associated 
with an increased incidence of bleeding and transfusions compared to the incidence seen when 
streptokinase was given alone. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no adequate data from the use of eptifibatide in pregnant women. 
 
Animal studies are insufficient with respect to effects on pregnancy, embryonal/foetal development, 
parturition or postnatal development (see section 5.3). The potential risk for humans is unknown.  
Eptifibatide Accord should not be used during pregnancy unless clearly necessary. 
 
Breast-feeding 
It is not known whether eptifibatide is excreted in human milk. Interruption of breast-feeding during 
the treatment period is recommended. 
 
4.7 Effects on ability to drive and use machines 
 
Not relevant, as Eptifibatide Accord is intended for use only in hospitalised patients. 
 
4.8 Undesirable effects 
 
The majority of adverse reactions experienced by patients treated with eptifibatide were generally 
related to bleeding or to cardiovascular events that occur frequently in this patient population. 
 
Clinical Trials 
The data sources used to determine adverse reaction frequency descriptors included two phase III 
clinical studies (PURSUIT and ESPRIT). These trials are briefly described below. 
 
PURSUIT: This was a randomized, double-blind evaluation of the efficacy and safety of eptifibatide 
versus placebo for reducing mortality and myocardial (re)infarction in patients with unstable angina or 
non-Q-wave myocardial infarction. 
 
ESPRIT: This was a double-blind, multicentre, randomized, parallel-group, placebo-controlled trial 
evaluating the safety and efficacy of eptifibatide therapy in patients scheduled to undergo non-
emergent percutaneous coronary intervention (PCI) with stent implantation. 
 
In PURSUIT, bleeding and non-bleeding events were collected from hospital discharge to the 30 day 
visit. In ESPRIT, bleeding events were reported at 48 hours, and non-bleeding events were reported at 
30 days. While Thrombolysis in Myocardial Infarction TIMI bleeding criteria were used to categorize 
the incidence of major and minor bleeding in both the PURSUIT and the ESPRIT trials, PURSUIT 
data was collected within 30 days while ESPRIT data was limited to events within 48 hours or 
discharge, whichever came first. 
 
The undesirable effects are listed by body system and frequency. Frequencies are defined as very 
common (≥ 1/10); common (≥ 1/100 to< 1/10); uncommon (≥ 1/1,000 to<  1/100); rare (≥ 1/10,000 to 
< 1/1000); very rare (< 1/10,000); not known (cannot be estimated from available data). These are 
absolute reporting frequencies without taking into account placebo rates. For a particular adverse 
reaction, if data was available from both PURSUIT and ESPRIT, then the highest reported incidence 
was used to assign adverse reaction frequency. 
 
 



20 

Note that causality has not been determined for all adverse reactions. 
 
Blood and Lymphatic System Disorder 
Very common Bleeding (major and minor bleeding including femoral artery access, 

CABG-related, gastrointestinal, genitourinary, retroperitoneal, intracranial, 
haematemesis, haematuria, oral/oropharyngeal, haemoglobin/haematocrit 
decreased and other). 

Uncommon Thrombocytopenia. 
Nervous System disorders 
Uncommon Cerebral ischaemia. 
Cardiac Disorders 
Common Cardiac arrest, ventricular fibrillation, ventricular tachycardia, congestive 

heart failure, atrioventricular block, atrial fibrillation. 
Vascular Disorders 
Common Shock, hypotension, phlebitis. 
 
Cardiac arrest, congestive heart failure, atrial fibrillation, hypotension, and shock, which are 
commonly reported events from the PURSUIT trial, were events related to the underlying disease. 
 
Administration of eptifibatide is associated with an increase in major and minor bleeding as classified 
by the criteria of the TIMI study group. At the recommended therapeutic dose, as administered in the 
PURSUIT trial involving nearly 11,000patients, bleeding was the most common complication 
encountered during eptifibatide therapy. The most common bleeding complications were associated 
with cardiac invasive procedures (coronary artery bypass grafting (CABG)-related or at femoral artery 
access site). 
 
Minor bleeding was defined in the PURSUIT trial as spontaneous gross haematuria, spontaneous 
haematemesis, observed blood loss with a haemoglobin decrease of more than 3 g/dl, or a 
haemoglobin decrease of more than 4 g/dl in the absence of an observed bleeding site. During 
treatment with eptifibatide in this study, minor bleeding was a very common complication (> 1/10, or 
13.1 % for eptifibatide versus 7.6 % for placebo). Bleeding events were more frequent in patients 
receiving concurrent heparin while undergoing PCI, when ACT exceeded 350 seconds (see section 
4.4, heparin use). 
 
Major bleeding was defined in the PURSUIT trial as either an intracranial haemorrhage or a decrease 
in haemoglobin concentrations of more than 5 g/dl. Major bleeding was also very common and 
reported more frequently with eptifibatide than with placebo in the PURSUIT study (> 1/10 or 10.8 % 
versus 9.3 %), but it was infrequent in the vast majority of patients who did not undergo CABG within 
30 days of inclusion in the study. In patients undergoing CABG, the incidence of bleeding was not 
increased by eptifibatide compared to the patients treated with placebo. In the subgroup of patients 
undergoing PCI, major bleeding was observed commonly, in 9.7 % of eptifibatide -treated patients vs. 
4.6 % of placebo-treated patients. 
 
The incidence of severe or life threatening bleeding events with eptifibatide was 1.9 % compared to 
1.1 % with placebo. The need for blood transfusions was increased modestly by eptifibatide treatment 
(11.8 % versus 9.3 % for placebo). 
 
Changes during eptifibatide treatment result from its known pharmacological action, i.e., inhibition of 
platelet aggregation. Thus, changes in laboratory parameters associated with bleeding (e.g. bleeding 
time) are common and expected. No apparent differences were observed between patients treated with 
eptifibatide or with placebo in values for liver function (SGOT/AST, SGPT/ALT, bilirubin, alkaline 
phosphatase) or renal function (serum creatinine, blood urea nitrogen). 
 
 
 
 



21 

Post-marketing experience 
 
Blood and lymphatic system disorders 
Very rare Fatal bleeding (the majority involved central and peripheral nervous system 

disorders: cerebral or intracranial haemorrhages); pulmonary haemorrhage, 
acute profound thrombocytopenia, haematoma. 

Immune system disorders 
Very rare Anaphylactic reactions. 
Skin and subcutaneous tissue disorders 
Very rare Rash, application site disorders such as urticaria. 
 
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 national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
The experience in humans with overdose of eptifibatide is extremely limited. There was no indication 
of severe adverse reactions associated with administration of accidental large bolus doses, rapid 
infusion reported as overdose or large cumulative doses. In the PURSUIT trial, there were 9 patients 
who received bolus and/or infusion doses more than double the recommended dose, or who were 
identified by the investigator as having received an overdose. There was no excessive bleeding in any 
of these patients, although one patient undergoing CABG surgery was reported as having had a 
moderate bleed. Specifically, no patients experienced an intracranial bleed. 
 
Potentially, an overdose of eptifibatide could result in bleeding. Because of its short half-life and rapid 
clearance, the activity of eptifibatide may be halted readily by discontinuing the infusion. Thus, 
although eptifibatide can be dialysed, the need for dialysis is unlikely. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antithrombotic agent (platelet aggregation inhibitors excl. heparin), ATC 
code: B01AC16 
 
Mechanism of action 
 
Eptifibatide, a synthetic cyclic heptapeptide containing six amino acids, including one cysteine amide 
and one mercaptopropionyl (desamino cysteinyl) residue, is an inhibitor of platelet aggregation and 
belongs to the class of RGD (arginine-glycine-aspartate)-mimetics. 
 
Eptifibatide reversibly inhibits platelet aggregation by preventing the binding of fibrinogen, von 
Willebrand factor and other adhesive ligands to the glycoprotein (GP) IIb/IIIa receptors. 
 
Pharmacodynamic effects 
 
Eptifibatide inhibits platelet aggregation in a dose- and concentration-dependent manner as 
demonstrated by ex vivo platelet aggregation using adenosine diphosphate (ADP) and other agonists to 
induce platelet aggregation. The effect of eptifibatide is observed immediately after administration of a 
180 microgram/kg intravenous bolus. When followed by a 2.0 microgram/kg/min continuous infusion, 
this regimen produces a > 80 % inhibition of ADP-induced ex vivo platelet aggregation, at physiologic 
calcium concentrations, in more than 80 % of patients. 

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22 

 
Platelet inhibition was readily reversed, with a return of platelet function towards baseline (> 50 % 
platelet aggregation) 4 hours after stopping a continuous infusion of 2.0 microgram/kg/min. 
Measurements of ADP-induced ex vivo platelet aggregation at physiologic calcium concentrations 
(Dphenylalanyl-L-prolyl-L-arginine chloromethyl ketone anticoagulant) in patients presenting with 
unstable angina and Non Q-Wave Myocardial Infarction showed a concentration-dependent inhibition 
with an IC50 (50 % inhibitory concentration) of approximately 550 ng/ml and an IC80 (80 % inhibitory 
concentration) of approximately 1,100 ng/ml. 
 
There is limited data with regards to platelet inhibition in patients with renal impairment. In patients 
with moderate renal impairment, (creatinine clearance 30 - 50 ml/min) 100 % inhibition was achieved 
at 24 hours following administration of 2 microgram/kg/min. In patients with severe renal impairment 
(creatinine clearance < 30 ml/min) administered 1microgram/kg/min , 80 % inhibition was achieved in 
more than 80 % of patients at 24 hours. 
 
Clinical efficacy and safety 
 
PURSUIT trial 
The pivotal clinical trial for Unstable Angina (UA)/Non-Q Wave Myocardial Infarction (NQMI) was 
PURSUIT. This study was a 726-center, 27-country, double-blind, randomised, placebo-controlled 
study in 10,948 patients presenting with UA or NQMI. Patients could be enrolled only if they had 
experienced cardiac ischemia at rest (≥ 10 minutes) within the previous 24 hours and had: 

• either ST-segment changes: ST depression > 0.5 mm of less than 30 minutes or persistent ST 
elevation > 0.5 mm not requiring reperfusion therapy or thrombolytic agents, T-wave 
inversion (> 1 mm), 

• or increased CK-MB. 
 
Patients were randomised to either placebo, eptifibatide 180 microgram/kg bolus followed by a 
2.0 microgram/kg/min infusion (180/2.0), or eptifibatide 180 microgram/kg bolus followed by a 
1.3 microgram/kg/min infusion (180/1.3). 
 
The infusion was continued until hospital discharge, until the time of coronary artery bypass grafting 
(CABG) or for up to 72 hours, whichever occurred first. If PCI was performed, the eptifibatide 
infusion was continued for 24 hours after the procedure, allowing for a duration of infusion up to 96 
hours. 
 
The 180/1.3 arm was stopped after an interim analysis, as prespecified in the protocol, when the two 
active-treatment arms appeared to have a similar incidence of bleeding. 
 
Patients were managed according to the usual standards of the investigational site; frequencies of 
angiography, PCI and CABG therefore differed widely from site to site and from country to country. 
Of the patients in PURSUIT, 13 % were managed with PCI during eptifibatide infusion, of whom 
approximately 50 % received intracoronary stents; 87 % were managed medically (without PCI during 
eptifibatide infusion). 
 
The vast majority of patients received acetylsalicylic acid (75-325 mg once daily). 
 
Unfractionated heparin was administered intravenously or subcutaneously at the physician’s 
discretion, most commonly as an intravenous bolus of 5,000 U followed by a continuous infusion of 
1,000 U/h. A target aPTT of 50-70 seconds was recommended. A total of 1,250 patients underwent 
PCI within 72 hours after randomisation, in which case they received intravenous unfractionated 
heparin to maintain an activated clotting time (ACT) of 300-350 seconds. 
 
The primary endpoint of the study was the occurrence of death from any cause or new myocardial 
infarction (MI) (evaluated by a blinded Clinical Events Committee) within 30 days of randomisation. 
The component MI could be defined as asymptomatic with enzymatic elevation of CK-MB or new Q 
wave. 



23 

 
Compared to placebo, eptifibatide administered as 180/2.0 significantly reduced the incidence of the 
primary endpoint events (table 1): this represents around 15 events avoided for 1,000 patients treated: 
 
Table 1: Incidence of Death/CEC-Assessed MI («Treated as Randomised» Population) 
 
Time Placebo Eptifibatide p-Value 
30 days 743/4,697 

(15.8 %) 
667/4,680 
(14.3 %) 

0.034a 

a: Pearson’s chi-square test of difference between placebo and eptifibatide. 
 
Results on the primary endpoint were principally attributed to the occurrence of myocardial infarction. 
The reduction in the incidence of endpoint events in patients receiving eptifibatide appeared early 
during treatment (within the first 72-96 hours) and this reduction was maintained through 6 months, 
without any significant effect on mortality. 
 
Patients most likely to benefit from eptifibatide treatment are those at high risk of developing 
myocardial infarction within the first 3-4 days after onset of acute angina. 
 
According to epidemiological findings, a higher incidence of cardiovascular events has been 
associated with certain indicators, for instance: 
-  age 
-  elevated heart rate or blood pressure 
-  persistent or recurrent ischemic cardiac pain 
-  marked ECG changes (in particular ST-segment abnormalities) 
-  raised cardiac enzymes or markers (e.g. CK-MB, troponins) and 
-  heart failure 
 
PURSUIT was conducted at a time when the standard of care of managing acute coronary syndromes 
was different from that of present times in terms of thienopyridine use and the routine use of 
intracoronary stents. 
 
ESPRIT trial 
ESPRIT (Enhanced Suppression of the Platelet IIb/IIIa Receptor with eptifibatide Therapy) was a 
double-blind, randomised, placebo-controlled trial (n= 2,064) for nonurgent PCI with intracoronary 
stenting. 
 
All patients received routine standard of care and were randomised to either placebo or eptifibatide (2 
bolus doses of 180 microgram/kg and a continuous infusion until discharge from hospital or a 
maximum of 18-24 hours). 
 
The first bolus and the infusion were started simultaneously, immediately before the PCI procedure 
and were followed by a second bolus 10 minutes after the first. The rate of infusion was 2.0 
microgram/kg/min for patients with serum creatinine ≤ 175 micromols/l or 1.0 microgram/kg/min for 
serum creatinine > 175 up to 350 micromols/l. 
 
In the eptifibatide arm of the trial, virtually all patients received aspirin (99.7 %), and 98.1 % received 
a thienopyridine, (clopidogrel in 95.4 % and ticlopidine in 2.7 %). On the day of PCI, prior to 
catheterization, 53.2 % received a thienopyridine (clopidogrel 52.7 %; ticlopidine 0.5 %) – mostly as a 
loading dose (300 mg or more). The placebo arm was comparable (aspirin 99.7 %, clopidogrel 95.9 %, 
ticlopidin 2.6 %). 
 
The ESPRIT trial used a simplified regimen of heparin during PCI that consisted of an initial bolus of 
60 units/kg, with a target ACT of 200 - 300 seconds. The primary endpoint of the trial was death (D), 
MI, urgent target vessel revascularisation (UTVR), and acute antithrombotic rescue with GP IIb/IIIa 
inhibitor therapy (RT) within 48 hours of randomisation. 
 



24 

MI was identified per the CK-MB core laboratory criteria. For this diagnosis, within 24 hours after the 
index PCI procedure, there had to be at least two CK-MB values ≥ 3 x the upper limit of normal; thus, 
validation by the CEC was not required. MI could also be reported following CEC adjudication of an 
investigator report. 
 
The primary endpoint analysis [quadruple composite of death, MI, urgent target vessel 
revascularisation (UTVR) and thrombolytic bail-out (TBO) at 48 hours] showed a 37 % relative and 
3.9 % absolute reduction in the eptifibatide group (6.6 % events versus 10.5 %, p = 0.0015). Results 
on the primary endpoint were mainly attributed to the reduction of enzymatic MI occurrence, 
identified as the occurrence of early elevation of cardiac enzymes after PCI (80 out of 92 MIs in the 
placebo group vs. 47 out of 56 MIs in the eptifibatide group). The clinical relevance of such enzymatic 
MIs is still controversial. 
 
Similar results were also obtained for the 2 secondary endpoints assessed at 30 days: a triple 
composite of death, MI and UTVR, and the more robust combination of death and MI. 
 
The reduction in the incidence of endpoint events in patients receiving eptifibatide appeared early 
during treatment. There was no increased benefit thereafter, up to 1 year. 
 
Prolongation of bleeding time 
Administration of eptifibatide by intravenous bolus and infusion causes up to a 5-fold increase in 
bleeding time. This increase is readily reversible upon discontinuation of the infusion with bleeding 
times returning towards baseline in approximately 6 (2-8) hours. When administered alone, 
eptifibatide has no measurable effect on prothrombin time (PT) or activated partial thromboplastin 
time (aPTT). 
 
EARLY-ACS trial 
EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Non-ST-segment Elevation Acute Coronary 
Syndrome) was a study of early routine eptifibatide versus placebo (with delayed provisional use of 
eptifibatide in the catheterization laboratory) used in combination with antithrombotic therapies (ASA, 
UFH, bivalirudin, fondaparinux or low molecular weight heparin), in subjects with high-risk NSTE 
ACS. Patients were to undergo an invasive strategy for further management after receiving study drug 
for 12 to 96 hours. Patients could be medically managed, proceed to coronary artery bypass graft 
(CABG), or undergo percutaneous coronary intervention (PCI). Unlike the approved posology in the 
EU, the study used a double bolus of study drug (separated by 10 minutes) before the infusion. 
 
Early routine eptifibatide in this high-risk NSTE-ACS optimally-treated population who were 
managed with an invasive strategy did not result in a statistically significant reduction in the 
composite primary endpoint of rate of death, MI, RI-UR, and TBO within 96 hours compared with a 
regimen of delayed provisional eptifibatide (9.3 % in early eptifibatide patients vs. 10.0 % in patients 
assigned to delayed provisional eptifibatide; odds ratio=0.920; 95 % CI=0.802-1.055; p=0.234). 
GUSTO severe/life threatening bleeding was uncommon and comparable in both treatment groups 
(0.8 %). GUSTO moderate or severe/life threatening bleeding occurred significantly more often with 
early routine eptifibatide (7.4 % vs. 5.0 % in delayed provisional eptifibatide group; p <0.001). Similar 
differences were noted for TIMI major haemorrhage (118 [2.5 %] in early routine use vs. 83 [1.8 %] in 
delayed provisional use; p=0.016). 
 
No statistically significant benefit of early routine eptifibatide strategy was demonstrated in the 
subgroup of patients who were managed medically or during the medical management periods prior to 
PCI or CABG. 
 
In a post hoc analysis of the EARLY ACS trial the risk benefit of dose reduction in patients with 
moderate renal impairment is inconclusive. The primary endpoint event rate was 11.9 % in patients 
who received a reduced dose (1microgram/kg/min) vs 11.2 % in patients who received the standard 
dose (2 microgram/kg/min) when eptifibatide was administered in the early routine fashion (p=0.81). 
With delayed provisional eptifibatide administration, the event rates were 10 % vs 11.5 % in patients 
who received reduced dose and standard dose respectively (p=0.61). TIMI major bleeding occurred in 



25 

2.7 % of patients who received a reduced dose (1microgram/kg/min) vs 4.2 % of patients who 
received the standard dose (2 microgram/kg/min) when eptifibatide was administered in the early 
routine fashion (p=0.36). With delayed provisional eptifibatide administration, the TIMI major events 
were 1.4 % vs 2.0 % in patients who received reduced dose and standard dose respectively 
(p=0.54).There were no notable differences observed with GUSTO severe bleeding rates. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
The pharmacokinetics of eptifibatide are linear and dose proportional for bolus doses ranging from 90 
to 250 microgram/kg and infusion rates from 0.5 to 3.0 microgram/kg/min.  
 
Distrobution 
For a 2.0 microgram/kg/min infusion, mean steady-state plasma eptifibatide concentrations range from 
1.5 to 2.2 microgram/ml in patients with coronary artery disease. These plasma concentrations are 
achieved rapidly when the infusion is preceded by a 180microgram/kg bolus.   
 
Biotransformation 
The extent of eptifibatide binding to human plasma protein is about 25 %. In the same population, 
plasma elimination half-life is approximately 2.5 hours, plasma clearance 55 to 80 ml/kg/hr and 
volume of distribution of approximately 185 to 260 ml/kg. 
 
Elimination 
In healthy subjects, renal excretion accounted for approximately 50 % of total body clearance; 
approximately 50 % of the amount cleared is excreted unchanged. In patients with moderate to severe 
renal insufficiency (creatinine clearance < 50 ml/min), the clearance of eptifibatide is reduced by 
approximately 50 % and steady-state plasma levels are approximately doubled. 
 
No formal pharmacokinetic interaction studies have been conducted. However, in a population 
pharmacokinetic study there was no evidence of a pharmacokinetic interaction between eptifibatide 
and the following concomitant medicinal products: amlodipine, atenolol, atropine, captopril, cefazolin, 
diazepam, digoxin, diltiazem, diphenhydramine, enalapril, fentanyl, furosemide, heparin, lidocaine, 
lisinopril, metoprolol, midazolam, morphine, nitrates, nifedipine, and warfarin. 
 
5.3 Preclinical safety data 
 
Toxicology studies conducted with eptifibatide include single and repeated dose studies in the rat, 
rabbit and monkey, reproduction studies in the rat and rabbit, in vitro and in vivo genetic toxicity 
studies, and irritation, hypersensitivity and antigenicity studies. No unexpected toxic effects for an 
agent with this pharmacologic profile were observed and findings were predictive of clinical 
experience, with bleeding effects being the principal adverse event. No genotoxic effects were 
observed with eptifibatide. 
 
Teratology studies have been performed by continuous intravenous infusion of eptifibatide in pregnant 
rats at total daily doses of up to 72 mg/kg/day (about 4 times the recommended maximum daily human 
dose on a body surface area basis) and in pregnant rabbits at total daily doses of up to 36 mg/kg/day 
(about 4 times the recommended maximum daily human dose on a body surface area basis). These 
studies revealed no evidence of impaired fertility or harm to the foetus due to eptifibatide. 
 
Reproduction studies in animal species where eptifibatide shows a similar pharmacologic activity as in 
humans are not available. Consequently these studies are not suitable to evaluate the toxicity of 
eptifibatide on reproductive function (see section 4.6). 
 
The carcinogenic potential of eptifibatide has not been evaluated in long-term studies. 
 
 
6. PHARMACEUTICAL PARTICULARS 



26 

 
6.1 List of excipients 
 
Citric acid monohydrate 
Sodium hydroxide 
Water for injections 
 
6.2 Incompatibilities 
 
Eptifibatide Accord is not compatible with furosemide. 
 
In the absence of compatibility studies, Eptifibatide Accord must not be mixed with other medicinal 
products except those mentioned in 6.6. 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). 
Store in the original package in order to protect from light. 
 
6.5 Nature and contents of container  
 
One 10 ml Type I glass vial, closed with a butyl rubber stopper and sealed with a flip-off aluminium 
seal. 
 
6.6 Special precautions for disposal and other handling 
 
Physical and chemical compatibility testing indicate that Eptifibatide Accord may be administered 
through an intravenous line with atropine sulfate, dobutamine, heparin, lidocaine, meperidine, 
metoprolol, midazolam, morphine, nitroglycerin, tissue plasminogen activator, or verapamil. 
Eptifibatide Accord is chemically and physically compatible with 0.9 % sodium chloride solution for 
infusion and with dextrose 5 % in Normosol R with or without potassium chloride up to 92 hours 
when stored at 20-25°C. Please refer to the Normosol R Summary of Product Characteristics for 
details on its composition. 
 
Before using, inspect the vial contents. Do not use if particulate matter or discolouration is present. 
Protection of Eptifibatide Accord solution from light is not necessary during administration. 
 
Discard any unused medicinal product after opening. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
8. MARKETING AUTHORISATION NUMBER  
 
EU/1/15/1065/002 
 



27 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation:11th January 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

http://www.ema.europa.eu/


28 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURERS RESPONSIBLE FOR BATCH 

RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING 

SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE 
MEDICINAL PRODUCT 

 



29 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
Accord Healthcare Limited 
Sage House  
319, Pinner Road 
North Harrow 
Middlesex HA1 4HF 
United Kingdom 
 
Wessling Hungary Kft 
Fòti ùt 56, Budapest 1047, 
Hungary 
 
Accord Healthcare Polska Sp.z o.o., 
ul. Lutomierska 50,95-200 Pabianice, Poland 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, section 4.2) 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached. 

 
 
 



30 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX III 

 
LABELLING AND PACKAGE LEAFLET 

  



31 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



32 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Eptifibatide Accord 0.75 mg/ml solution for infusion 
eptifibatide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of solution for infusion contains 0.75 mg of eptifibatide. 
 
One 100 ml vial contains 75 mg of eptifibatide. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Citric acid monohydrate, sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for infusion 
 
1 vial of 100 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use 
Read the package leaflet before use.  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP:  
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator(2°C - 8°C).  
 
Store in the original package in order to protect from light. 
 



33 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1065/001   
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
PC: 
SN: 
NN: 
  



34 

PARTICULARS TO APPEAR ON IMMEDIATE PACKAGING UNITS 
 
LABEL for 100 ml vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Eptifibatide Accord 0.75 mg/ml solution for infusion 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One 100 ml vial contains 75 mg of eptifibatide. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Citric acid monohydrate, sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for infusion 
100 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
I.V. use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator (2°C - 8°C). 
Store in the original package in order to protect from light. 
 



35 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR  WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
 APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1065/001 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



36 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Eptifibatide Accord 2 mg/ml solution for injection 
eptifibatide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of solution for injection contains 2 mg of eptifibatide. 
 
One 10 ml vial contains 20 mg of eptifibatide. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Citric acid monohydrate, sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
1 vial of 10 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use 
Read the package leaflet before use.  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP : 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator (2°C - 8°C).  
Store in the original package in order to protect from light. 
 



37 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1065/002   
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 

 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
PC: 
SN: 
NN: 
  



38 

 
 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL for 10 ml vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Eptifibatide Accord 2 mg/ml solution for injection 
eptifibatide 
 
Intravenous use  
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
20 mg/10 ml 
 
 
6. OTHER 
 
 
 

  



39 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



40 

Package leaflet: Information for the patient 
 

Eptifibatide Accord 0.75 mg/ml solution for infusion 
eptifibatide 

 
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 hospital pharmacist or nurse. 
- If you get any side effects talk to your doctor or hospital pharmacist or nurse. This includes any 

possible side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet:  
1. What Eptifibatide Accord is and what it is used for 
2. What you need to know before you are given Eptifibatide Accord 
3. How to use Eptifibatide Accord 
4. Possible side effects 
5. How to store Eptifibatide Accord 
6. Contents of the pack and other information 
 
 
1. What Eptifibatide Accord is and what it is used for 
 
Eptifibatide Accord is an inhibitor of platelet aggregation. This means that it helps to prevent blood 
clots from forming.  
 
It is used in adults with manifestation of severe coronary insufficiency defined as spontaneous and 
recent chest pain with electrocardiographic abnormalities or biological changes. It is usually given 
with aspirin and unfractionated heparin. 
 
 
2. What you need to know before you are given Eptifibatide Accord 
 
Do not use Eptifibatide Accord: 
 
- if you are allergic to eptifibatide or any of the other ingredients of this medicine (listed in section 

6). 
- if you have recently had bleeding from your stomach, intestines, bladder or other organs, for 

example if you have seen abnormal blood in your stool or urine (except from menstrual bleeding) 
in the past 30 days. 

- if you have had a stroke within the past 30 days or any haemorrhagic stroke (also, be sure your 
doctor knows if you ever had a stroke). 

- if you have had a brain tumour or a condition that affects the blood vessels around the brain. 
- if you had a major operation or severe injury during the past 6 weeks. 
- if you have or have had bleeding problems. 
- if you have or have had difficulty with your blood clotting or a low blood platelet count. 
- if you have or have had severe hypertension (high blood pressure). 
- if you have or have had severe kidney or liver problems. 
- if you have been treated with another medicine of the same type as Eptifibatide Accord. 
 
Please tell your doctor if you have had any of these conditions. If you have any questions, ask your 
doctor or hospital pharmacist or nurse. 
 
Warnings and precautions 
- Eptifibatide Accord is recommended for use only in adult, hospitalised patients in coronary care 

units. 
- Eptifibatide Accord is not intended for use in children or adolescents less than 18 years of age. 



41 

Before and during your treatment with Eptifibatide Accord, samples of your blood will be tested as a 
safety measure to limit the possibility of unexpected bleeding. 
During use of Eptifibatide Accord, you will be checked carefully for any signs of unusual or 
unexpected bleeding. 
 

 Talk to your doctor or hospital pharmacist or nurse before using Eptifibatide Accord. 
 
Other medicines and Eptifibatide Accord 
To avoid the possibility of interactions with other medicines please tell your doctor or hospital 
pharmacist or nurse if you are taking or have recently taken or might take any other medicines, 
including medicines obtained without a prescription. Particularly: blood thinners (oral anticoagulants) 
or medicines that prevent blood clots, including warfarin, dipyridamole, ticlopidine, aspirin (except 
those that you may be given as part of Eptifibatide Accord treatment).  
 
Pregnancy and breast-feeding 
Eptifibatide Accord is not usually recommended for use during pregnancy. Tell your doctor if you are 
pregnant, think you might be pregnant or are planning to have a baby. Your doctor will weigh up the 
benefit to you against the risk to your baby of using Eptifibatide Accord while you are pregnant. 
 
If you are breast-feeding a baby, breast-feeding should be interrupted during the treatment period. 
 
 
3. How to use Eptifibatide Accord 
 
Eptifibatide Accord is given into the vein by direct injection followed by an infusion (drip solution). 
The dose given is based on your weight. The recommended dose is 180 microgram/kg administered as 
a bolus (rapid intravenous injection), followed by an infusion (drip solution) of 
2 microgram/kg/minute for up to 72 hours. If you have kidney disease, the infusion dose may be 
reduced to 1 microgram/kg/minute. 
 
If percutaneous coronary intervention (PCI) is performed during Eptifibatide Accord therapy, the 
intravenous solution may be continued for up to 96 hours. 
 
You must also be given doses of aspirin and heparin (if not contraindicated in your case). 
 
If you have any further questions on the use of this product, ask your doctor or hospital pharmacist or 
nurse. 
 
 
4.  Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  
 
Very common side effects 
These may affect more than 1 in 10 people 
- minor or major bleeding, (for example, blood in urine, blood in stool, vomiting blood, or bleeding 

with surgical procedures). 
- anaemia (decreased number of red blood cells).  
 
Common side effects 
These may affect up to 1 in 10 people 
- inflammation of a vein. 
 
Uncommon side effects 
These may affect up to 1 in 100 people 
- reduction in the number of platelets (blood cells necessary for blood clotting). 
- reduced blood flow to the brain. 



42 

 
Very rare side effects 
These may affect up to 1 in 10,000 people 
- serious bleeding (for example, bleeding inside the abdomen, inside the brain, and into the lungs). 
- fatal bleeding. 
- severe reduction in the number of platelets (blood cells necessary for blood clotting). 
- skin rash (such as hives). 
- sudden, severe allergic reaction. 
 
If you notice any signs of bleeding, notify your doctor or hospital pharmacist or nurse immediately. 
Very rarely, bleeding has become severe and even fatal. Safety measures to prevent this from 
happening include blood tests and careful checking by the healthcare professionals taking care of you.  
 
If you develop severe allergic reaction or hives, notify your doctor or hospital pharmacist or nurse 
immediately. 
 
Other events that may occur in patients, who require this type of treatment, include those that are 
related to the condition you are having treated, such as rapid or irregular heartbeat, low blood pressure, 
shock or cardiac arrest. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or hospital pharmacist or nurse. 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 Eptifibatide Accord 
 
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 the vial after (EXP). The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C). 
 
Keep the vial in the outer package in order to protect from light. However, protection of Eptifibatide 
Accord solution from light is not necessary during administration. 
 
Before using, the vial contents should be inspected. 
Eptifibatide Accord should not be used if it is noticed that particulate matter or discoloration is present.  
 
Any unused medicine after opening should be thrown away.   
 
Do not throw away any medicines via wastewater or household waste. Ask your hospital pharmacist 
how to throw away medicines you no longer use. 
 

 
6. Contents of the pack and other information 
 
What Eptifibatide Accord contains 
− The active substance is eptifibatide.  

Eptifibatide Accord 0.75 mg/ml: Each ml of solution for infusion contains 0.75 mg of 
eptifibatide. One vial of 100 ml of solution for infusion contains 75 mg of eptifibatide.  

− The other ingredients are citric acid monohydrate, sodium hydroxide and water for injections. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


43 

What Eptifibatide Accord looks like and contents of the pack 
Eptifibatide Accord 0.75 mg/ml solution for infusion: 100 ml vial, pack of one vial.  
 
Eptifibatide Accord 0.75 mg/ml: The clear, colourless solution is contained in a 100 ml glass vial, 
which is closed with a butyl rubber stopper and sealed with a flip-off aluminium seal. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder: 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
Manufacturer: 
 
Accord Healthcare Limited 
Sage House 
319, Pinner Road, Harrow 
Middlesex HA1 4HF 
United Kingdom 
 
Wessling Hungary Kft 
Fòti ùt 56, Budapest 1047, 
Hungary 
 
Accord Healthcare Polska Sp.z o.o., 
ul. Lutomierska 50,95-200 Pabianice, Poland 
 
 
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 

 

http://www.ema.europa.eu/


44 

Package leaflet: Information for the patient 
 

Eptifibatide Accord 2 mg/ml solution for injection 
eptifibatide 

 
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 hospital pharmacist or nurse. 
- If you any get side effects talk to your doctor or hospital pharmacist or nurse. This includes any 

possible side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet:  
1. What Eptifibatide Accord is and what it is used for 
2. What you need to know before you are given Eptifibatide Accord 
3. How to use Eptifibatide Accord 
4. Possible side effects 
5. How to store Eptifibatide Accord 
6. Contents of the pack and other information 
 
 
1. What Eptifibatide Accord is and what it is used for 
 
Eptifibatide Accord is an inhibitor of platelet aggregation. This means that it helps to prevent blood clots 
from forming. 
 
It is used in adults with manifestation of severe coronary insufficiency defined as spontaneous and 
recent chest pain with electrocardiographic abnormalities or biological changes. It is usually given 
with aspirin and unfractionated heparin. 
 
 
2. What you need to know before you are given Eptifibatide Accord 
 
Do not use Eptifibatide Accord: 
− if you are allergic to eptifibatide or any of the other ingredients of this medicine (listed in section 

6). 
− if you have recently had bleeding from your stomach, intestines, bladder or other organs, for 

example if you have seen abnormal blood in your stool or urine (except from menstrual bleeding) 
in the past 30 days. 

− if you have had a stroke within the past 30 days or any haemorrhagic stroke (also, be sure your 
doctor knows if you ever had a stroke). 

− if you have had a brain tumour or a condition that affects the blood vessels around the brain. 
− if you had a major operation or severe injury during the past 6 weeks. 
− if you have or have had bleeding problems. 
− if you have or have had difficulty with your blood clotting or a low blood platelet count. 
− if you have or have had severe hypertension (high blood pressure). 
− if you have or have had severe kidney or liver problems. 
− if you have been treated with another medicine of the same type as Eptifibatide Accord. 
 
Please tell your doctor if you have had any of these conditions. If you have any questions, ask your 
doctor or hospital pharmacist or nurse. 
 



45 

Warnings and precautions  
 
− Eptifibatide Accord is recommended for use only in adult, hospitalised patients in coronary care 

units. 
− Eptifibatide Accord is not intended for use in children or adolescents less than 18 years of age. 
− Before and during your treatment with Eptifibatide Accord, samples of your blood will be tested 

as a safety measure to limit the possibility of unexpected bleeding. 
− During use of Eptifibatide Accord, you will be checked carefully for any signs of unusual or 

unexpected bleeding. 
  

Talk to your doctor or hospital pharmacist or nurse before using Eptifibatide Accord. 
 
Other medicines and Eptifibatide Accord 
To avoid the possibility of interactions with other medicines please tell your doctor or hospital 
pharmacist or nurse if you are taking or have recently taken or might take any other medicines, 
including medicines obtained without a prescription. Particularly: 
− blood thinners (oral anticoagulants) or 
− medicines that prevent blood clots, including warfarin, dipyridamole, ticlopidine, aspirin (except 

those that you may be given as part of Eptifibatide Accord treatment).  
 
Pregnancy and breast-feeding 
Eptifibatide Accord is not usually recommended for use during pregnancy. Tell your doctor if you are 
pregnant, think you might be pregnant or are planning to have a baby. Your doctor will weigh up the 
benefit to you against the risk to your baby of using Eptifibatide Accord while you are pregnant. 
 
If you are breast-feeding a baby, breast-feeding should be interrupted during the treatment period. 
 
 
3. How to use Eptifibatide Accord 
 
Eptifibatide Accord is given into the vein by direct injection followed by an infusion (drip solution). The 
dose given is based on your weight. The recommended dose is 180 microgram/kg administered as a 
bolus (rapid intravenous injection), followed by an infusion (drip solution) of 2 microgram/kg/minute for 
up to 72 hours. If you have kidney disease, the infusion dose may be reduced to 1 
microgram/kg/minute. 
 
If percutaneous coronary intervention (PCI) is performed during Eptifibatide Accord therapy, the 
intravenous solution may be continued for up to 96 hours. 
 
You must also be given doses of aspirin and heparin (if not contraindicated in your case). 
 
If you have any further questions on the use of this product, ask your doctor or hospital pharmacist or 
nurse. 
 
 
4.  Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  
 
Very common side effects 
These may affect more than 1 in 10 people 



46 

− minor or major bleeding, (for example, blood in urine, blood in stool, vomiting blood, or bleeding 
with surgical procedures). 

− anaemia (decreased number of red blood cells). 
 
Common side effects 
These may affect up to 1 in 10 people 
− inflammation of a vein. 
 
Uncommon side effects 
These may affect up to 1 in 100 people 
− reduction in the number of platelets (blood cells necessary for blood clotting). 
− reduced blood flow to the brain. 
 
Very rare side effects 
These may affect up to 1 in 10,000 people 
− serious bleeding (for example, bleeding inside the abdomen, inside the brain, and into the lungs) 
− fatal bleeding. 
− severe reduction in the number of platelets (blood cells necessary for blood clotting). 
− skin rash (such as hives). 
− sudden, severe allergic reaction. 
 
If you notice any signs of bleeding, notify your doctor or hospital pharmacist or nurse immediately. 
Very rarely, bleeding has become severe and even fatal. Safety measures to prevent this from 
happening include blood tests and careful checking by the healthcare professionals taking care of you.  
 
If you develop severe allergic reaction or hives, notify your doctor or hospital pharmacist or nurse 
immediately. 
 
Other events that may occur in patients, who require this type of treatment, include those that are 
related to the condition you are having treated, such as rapid or irregular heartbeat, low blood pressure, 
shock or cardiac arrest. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or hospital pharmacist or nurse. 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 Eptifibatide Accord 
 
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 the vial after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C). 
 
Keep the vial in the outer package in order to protect from light. However, protection of Eptifibatide 
Accord solution from light is not necessary during administration. 
 
Before using, the vial contents should be inspected. 
 
Eptifibatide Accord should not be used if it is noticed that particulate matter or discoloration is 
present.  
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


47 

Any unused medicine after opening should be thrown away. 
 
Do not throw away any medicines via wastewater or household waste. Ask your hospital pharmacist 
how to throw away medicines you no longer use. 
 
 
6. Contents of the pack and other information 
 
What Eptifibatide Accord contains 
The active substance is eptifibatide.  
 
Eptifibatide Accord 2 mg/ml: Each ml of solution for injection contains 2 mg of eptifibatide. One 
vial of 10 ml solution for injection contains 20 mg of eptifibatide. 
The other ingredients are citric acid monohydrate, sodium hydroxide and water for injections. 
 
What Eptifibatide Accord looks like and contents of the pack 
Eptifibatide Accord 2 mg/ml solution for injection: 10 ml vial, pack of one vial. 
 
Eptifibatide Accord 2 mg/ml:  The clear, colourless solution is contained in a 10 ml glass vial, which 
is closed with a butyl rubber stopper and sealed with a flip-off aluminium seal. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder: 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
Manufacturer: 
 
Accord Healthcare Limited 
Sage House 
319, Pinner Road, Harrow 
Middlesex HA1 4HF 
United Kingdom 
 
Wessling Hungary Kft 
Fòti ùt 56, Budapest 1047, 
Hungary 
 
Accord Healthcare Polska Sp.z o.o., 
ul. Lutomierska 50,95-200 Pabianice, Poland 
 
 
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 

 

http://www.ema.europa.eu/

	ANNEX I
	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET