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Eli Lilly and Company (Ireland) Limited

Eli Lilly and Company (Ireland) Limited
Hyde House, 65, Adelaide Road, Dublin 2,
Telephone: +353 1 661 4377
Fax: +353 1 661 4476
WWW: http://www.lilly.ie
Medical Information Direct Line: +44 (0)1256 315 000
Medical Information Facsimile: +44 (0)1256 775 569
Summary of Product Characteristics last updated on medicines.ie: 29/11/2011
SPC ReoPro

When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 29/11/2011 and displayed until Current
Reasons for adding or updating:
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   11-Nov-2011
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company



4.         Clinical particulars

 

4.2       Posology and method of administration

 

Added (bold) Deleted (strikethrough):

 

Children Paediatric patients:

ReoPro is not recommended for use in children and adolescents paediatric patients below age 18 due to a lack of data on safety and efficacy.

 

4.4       Special warnings and precautions for use

 

Thrombocytopenia

 

Added:

 

Thrombocytopenia, including severe thrombocytopenia, has been observed with ReoPro administration (See section 4.8).  In clinical studies, most cases of severe thrombocytopenia (< 50,000 cells/mL) occurred within the first 24 hours of ReoPro administration.

 

Hypersensitivity

 

Added (bold) Deleted (strikethrough):

 

Hypersensitivity or allergic reactions have been observed rarely following treatment with ReoPro. Nevertheless, anaphylaxisAnaphylactic reactions (sometimes fatal) have been reported very rarely and may potentially occur at any time during administration.

 

Added (bold) Deleted (strikethrough):

 

Children Paediatric patients or patients older than 80 Years:

 

Children Paediatric patients or patients older than 80 years have not been studied.

 

4.8          Undesirable effects

 

Added (bold) Deleted (strikethrough):

 

General disorders and administration site conditions

Common:

Chest pain, pyrexia, puncture site pain, abdominal pain

 

Respiratory, thoracic and mediastinal disorders

Rare:

Adult respiratory distress syndrome, Pulmonary haemorrhage

Vascular disorders

Common:

Bleeding; hypotension, peripheral oedema

Uncommon:

Intracranial haemorrhage

Rare:

Pulmonary haemorrhage

 

 

 

 

Added:

 

Post-Marketing:

In addition to the previously mentioned clinical trials safety data, spontaneous adverse events (AEs) from the worldwide postmarketing experience with ReoPro are listed below.

The frequency provided is a reflection of reporting rates for spontaneous adverse drug reactions and does not represent true incidence or frequency as seen with clinical trials or epidemiologic studies.

 

AEs reported in the post-marketing period by System Organ Class include:

Gastrointestinal Disorders: very rare - gastrointestinal haemorrhage (see section 4.4, paragraph on Bleeding precautions, GI bleeding prophylaxis)

General Disorders and Administration Site Conditions: very rare – anaphylactic reactions (see section 4.4, paragraph on Hypersensitivity)

 

Deleted:

 

There were no reports of serious allergic reactions or anaphylaxis.

 

 

 

5.         PHARMACOLOGICAL PROPERTIES

 

5.1       Pharmacodynamic properties

 

Added (bold) Deleted (strikethrough):

 

Pharmacotherapeutic group: Platelet aggregation inhibitors excl. Heparinantithrombotic agents, platelet aggregation inhibitors excl. heparin, ATC code: B01A C13.

 

 

 

9.             DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Added (bold) Deleted (strikethrough):

 

Date of first authorisation:                            23 July 1995

Date of last renewal of the authorisation:  22 March 200510

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date:

 

11 November 2011

Updated on 23/03/2011 and displayed until 29/11/2011
Reasons for adding or updating:
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   15-Mar-2011
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company



10.          DATE OF REVISION OF THE TEXT

 

New date:

 

15-March-2011

Updated on 11/02/2011 and displayed until 23/03/2011
Reasons for adding or updating:
  • Change to section 10 - Date of revision of the text
  • Change to section 7 - Marketing authorisation holder
Date of revision of text on the SPC:   01-Jan-2011
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company



Changed:

 

7.         MARKETING AUTHORISATION HOLDER

 

Janssen Biologics B.V.

Einsteinweg 101

2333 CB Leiden

The Netherlands

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date:

 

January 2011

Updated on 07/08/2009 and displayed until 11/02/2011
Reasons for adding or updating:
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 6.3 - Shelf life
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 10 - Date of revision of the text
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 8 - MA number
  • Change to section 6.2 - Incompatibilities
Date of revision of text on the SPC:   17-Oct-2007
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company



Note: This SPC has changed in it’s entirety due to QRD updates.

 

2.             QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Added (bold) Deleted (strikethrough):

 

Abciximab 2mg/ml. ReoPro 2 mg/mL contains 10 mg abciximab in 5 mL water for injection.

 

Deleted:

 

One vial contains 10mg.

 

Added (bold):

 

For a full list of excipients, see section 6.1.

 

 

 

3.             PHARMACEUTICAL FORM

 

Added:

 

ReoPro is a colourless and clear liquid.

 

 

 

4.             CLINICAL PARTICULARS

 

4.1           Therapeutic indications

 

Added (bold) Deleted (strikethrough):

 

ReoPro is indicated as an adjunct to heparin and aspirin acetylsalicylic acid for:

 

4.2          Posology and method of administration

 

Added:

 

ReoPro should only be administered in conjunction with extensive specialist medical and nursing care. In addition, there must be availability of laboratory tests of haematology function and facilities for administration of blood products.

 

Added:

 

Children:

ReoPro is not recommended for use in children and adolescents below age 18 due to a lack of data on safety and efficacy.

 

For details on the preparation for administration see section 6.6.

 

Deleted:

 

Administration Instructions:

 

1.             Parenteral drug products should be inspected visually for particulate matter prior to administration.  Preparations of ReoPro containing visibly opaque particles should NOT be used.

 

2.             Hypersensitivity reactions should be anticipated whenever protein solutions such as ReoPro are administered.  Adrenaline, dopamine, theophylline, antihistamines, and corticosteroids should be available for immediate use.  If symptoms of an allergic reaction or anaphylaxis appear, the infusion should be stopped immediately.  Subcutaneous administration of 0.3 to 0.5ml of aqueous adrenaline (1:1000 dilution), and use of corticosteroids, respiratory assistance, and other resuscitative measures are essential.

 

3.             As with all parenteral drug products, aseptic procedures should be used during the administration of ReoPro.

 

4.             Withdraw the necessary amount of ReoPro for the bolus injection into a syringe.  Filter the bolus injection using a sterile, non-pyrogenic, low protein-binding 0.2/0.22µm or 5.0µm syringe filter.  The bolus should be administered over one (1) minute.

 

5.             Withdraw the necessary amount of ReoPro for the continuous infusion into a syringe.  Inject into an appropriate container of sterile 0.9% saline or 5% dextrose and infuse at the calculated rate via a continuous infusion pump.  The continuous infusion should be filtered either upon admixture, using a sterile, non-pyrogenic, low protein-binding 0.2µm/0.22µm or 5.0µm syringe filter, or upon administration, using an in-line, sterile, non-pyrogenic, low protein-binding 0.2µm or 0.22µm filter.  Discard the unused portion at the end of the infusion period.

 

6.             Although incompatibilities have not been shown with intravenous infusion fluids or commonly used cardiovascular drugs, it is recommended that ReoPro be administered in a separate intravenous line whenever possible and not mixed with other medications.

7.             No incompatibilities have been observed with glass bottles or polyvinyl chloride bags or administration sets.

 

4.3          Contra-indications

 

Added (bold) Deleted (strikethrough):

 

ReoPro should not be administered to patients with known sensitivityhypersensitivity to abciximab, to any component of the product, or to murine monoclonal antibodies or to papain. Trace amounts of papain resulting from the production process may be present.

 

Added (bold):

 

Since there are only limited data available, use of ReoPro in severe renal failure patients requiring haemodialysis is contraindicated (see section 4.4, paragraph on Renal disease).

 

4.4           Special warnings and precautions for use

 

Deleted:

 

Requirement for Specialist Facilities:

 

ReoPro should only be administered in conjunction with extensive specialist medical and nursing care.  In addition, there must be availability of laboratory tests of haematology function and facilities for administration of blood products.

 

Added (bold) Deleted (strikethrough):

 

Concomitant aspirinacetylsalicylic acid and heparin therapy

 

ReoPro should be used as an adjunct to aspirinacetylsalicylic acid and heparin therapy.

 

Aspirin Concomitant acetylsalicylic acid therapy

 

AspirinAcetylsalicylic acid should be administered orally at a daily dose of approximately, but not less than, 300mg.

 

HeparinConcomitant heparin therapy for percutaneous coronary intervention

 

Deleted:

 

1.             Percutaneous Coronary Intervention

 

Heparin Infusion After PTCA

 

Added (bold) Deleted (strikethrough):

 

(see ‘Bleeding Precautions: Femoral Artery Sheath Removal’ paragraph on Bleeding Precautions - Femoral artery access site).

 

Added (bold) Deleted (strikethrough):

 

2.             Stabilisation of Unstable Angina Concomitant heparin therapy for stabilisation of unstable angina

 

Added (bold) Deleted (strikethrough):

 

Following angioplasty, heparin management is outlined above under ‘1. Percutaneous Coronary Intervention’.as described in the paragraph on Concomitant heparin therapy for percutaneous coronary intervention.

 

Added:

 

Potential bleeding sites

Careful attention should be paid to all potential bleeding sites, including arterial and venous puncture sites, catheter insertion sites, cut down sites, and needle puncture sites.

 

Added (bold) Deleted (strikethrough):

 

After sheath removal, intravenous access should be maintained until bleeding is controlled (see ‘Overdose: Uncontrolled bleeding’ paragraph on Transfusion to restore platelet function).

 

Deleted:

 

Potential Bleeding Sites

 

Careful attention should be paid to all potential bleeding sites, including arterial and venous puncture sites, catheter insertion sites, cut down sites, and needle puncture sites.

 

Retroperitoneal Bleeding

 

Added (bold) Deleted (strikethrough):

 

 (see paragraph on Bleeding Precautions - Femoral Artery Access Site Bleeding Precautions: Femoral Artery Access Site’).

 

Pulmonary (Mostly Alveolar) Haemorrhage

 

If confirmed, ReoPro and all anticoagulant and other antiplatelet drugs medicinal products should immediately be discontinued.

 

General Nursing Care

 

SalineSodium chloride solution or heparin locks should be considered for blood drawing.  Vascular puncture sites should be documented and monitored.  Gentle care should be provided when removing dressings.

 

Deleted:

 

Restoration of Platelet Function

 

Transfusion of donor platelets has been shown to restore platelet function following ReoPro administration in animal studies, and transfusions of fresh random donor platelets have been given empirically to restore platelet function in humans.  In the event of serious uncontrolled bleeding or the need for emergency surgery, ReoPro should be discontinued.  In the majority of patients, bleeding time returns to normal within 12 hours.  If bleeding time remains prolonged and/or there is a marked inhibition of platelet function and/or if rapid haemostasis is required and/or in case(s) where haemostasis is not adequately restored, consideration should be given to seeking advice of a haematologist experienced in the diagnosis and management of bleeding disorders.

 

If rapid haemostasis is required, therapeutic doses of platelets may be administered (at least 5.5 x 1011 platelets).  Redistribution of ReoPro from endogenous platelet receptors to platelets, which have been transfused, may take place.  A single transfusion may be sufficient to reduce receptor blockade to 60% to 70%, at which level platelet function is restored.  Repeat platelet transfusions may be required to maintain haemostasis.

 

Use of Thrombolytics, Anticoagulants, and Other Antiplatelet Agents:

 

Added:

 

Thrombocytopenia

 

To evaluate the possibility of thrombocytopenia, platelet counts should be monitored prior to treatment, 2 to 4 hours following the bolus dose of ReoPro and at 24 hours. If a patient experiences an acute platelet decrease, additional platelet counts should be determined. These platelet counts should be drawn in three separate tubes containing ethylenediaminetetraacetic acid (EDTA), citrate and heparin, respectively, to exclude pseudothrombocytopenia, due to in vitro anticoagulant interaction. If true thrombocytopenia is verified, ReoPro should be immediately discontinued and the condition appropriately monitored and treated. A daily platelet count should be obtained until it returns to normal. If a patient's platelet count drops to 60,000 cells/µL, heparin and acetylsalicylic acid should be discontinued. If a patient's platelet count drops below 50,000 cells/µL, transfusion of platelets should be considered, especially if the patient is bleeding and/or invasive procedures are planned or ongoing. If the patient’s platelet count drops below 20,000 cells/µL, platelets should be transfused. The decision to use platelet transfusion should be based upon clinical judgment on an individual basis. Thrombocytopenia has been observed at higher rates following readministration (see paragraph on Readministration).

 

Transfusion to restore platelet function

 

In the event of serious uncontrolled bleeding or the need for emergency surgery, ReoPro should be discontinued.

 

In the majority of patients, bleeding time returns to normal within 12 hours. If bleeding time remains prolonged and/or there is a marked inhibition of platelet function and/or if rapid haemostasis is required and/or in case(s) where haemostasis is not adequately restored, consideration should be given to seeking advice of a haematologist experienced in the diagnosis and management of bleeding disorders. Transfusion of donor platelets has been shown to restore platelet function following ReoPro administration in animal studies and transfusions of fresh random donor platelets have been given empirically to restore platelet function in humans.

 

When considering the need to transfuse patients, the patient's intravascular volume should be assessed. If hypovolaemic, then the intravascular volume should be adequately restored with crystalloids. In asymptomatic patients, normovolaemic anaemia (haemoglobin 7-10 g/dL) can be well tolerated; transfusion is not indicated unless a deterioration in vital signs is seen or unless the patient develops signs and symptoms. In symptomatic patients (e.g., syncope, dyspnoea, postural hypotension, tachycardia), crystalloids should be used to replace intravascular volume.

 

If symptoms persist, the patient should receive transfusions with packed red blood cells or whole blood on a unit-by-unit basis to relieve symptoms; one unit may be sufficient.

 

If rapid haemostasis is required, therapeutic doses of platelets may be administered (at least 5.5 x 1011 platelets). Redistribution of ReoPro from endogenous platelet receptors to platelets, which have been transfused, may take place. A single transfusion may be sufficient to reduce receptor blockade to 60% to 70% at which level platelet function is restored. Repeat platelet transfusions may be required to maintain haemostasis.

 

Specific guidelines for access site bleeding are given above under the paragraph on Bleeding precautions - Femoral artery access site.

 

Use of thrombolytics, anticoagulants and other antiplatelet agents

 

Added (bold) Deleted (strikethrough):

 

Because ReoPro inhibits platelet aggregation, caution should be employed when used with other drugs medicinal products affecting haemostasis, such as heparin, oral anticoagulants, such as warfarin, thrombolytics, and antiplatelet agents other than aspirinacetylsalicylic acid, such as dipyridamole, ticlopidine, or low molecular weight dextrans (see section 4.5).

 

The risk of bleeding and ICH appears higher the sooner ReoPro is administered after the application of the thrombolytic (see section 4.8, paragraph on Other vascular disorders).

 

Deleted:

 

The GUSTO V trial randomised 16,588 patients with acute myocardial infarction to treatment with combined ReoPro and half-dose reteplase or full dose reteplase alone.  The incidence of moderate or severe non-intracranial bleeding was increased in those patients receiving ReoPro and half-dose reteplase versus those receiving reteplase alone (4.6% versus 2.3%, respectively).

 

Added (bold) Deleted (strikethrough):

 

If urgent intervention is required for refractory symptoms in a patient receiving ReoPro (or who has received the drugmedicinal product in the previous 48 hours),

 

Deleted:

 

Thrombocytopenia:

 

To evaluate the possibility of thrombocytopenia, platelet counts should be monitored prior to treatment, 2 to 4 hours following the bolus dose of ReoPro, and at 24 hours.  If a patient experiences an acute platelet decrease, additional platelet counts should be determined.  These platelet counts should be drawn in three separate tubes containing ethylenediaminetetraacetic acid (EDTA), citrate, and heparin, respectively, to exclude pseudothrombocytopenia due to in vitro anticoagulant interaction.  If true thrombocytopenia is verified, ReoPro should be immediately discontinued and the condition appropriately monitored and treated.  A daily platelet count should be obtained until it returns to normal.  If a patient’s platelet count drops to 60,000 cells/µl, heparin and aspirin should be discontinued.  If a patient’s platelet count drops below 50,000 cells/µl, transfusion of platelets should be considered, especially if the patient is bleeding and/or invasive procedures are planned or ongoing. If the patient’s platelet count drops below 20,000 cells/µl, platelets should be transfused.  The decision to use platelet transfusion should be based upon clinical judgment on an individual basis.

 

Added:

 

Hypersensitivity

 

Hypersensitivity reactions should be anticipated whenever protein solutions such as ReoPro are administered. Adrenaline, dopamine, theophylline, antihistamines and corticosteroids should be available for immediate use. If symptoms of an allergic reaction or anaphylaxis appear, the infusion should be stopped immediately. Subcutaneous administration of 0.3 to 0.5 mL of aqueous adrenaline (1:1000 dilution), and use of corticosteroids, respiratory assistance and other resuscitative measures are essential.

 

Hypersensitivity or allergic reactions have been observed rarely following treatment with ReoPro. Nevertheless, anaphylaxis may potentially occur at any time during administration.

 

Readministration:

 

Added (bold) Deleted (strikethrough):

 

Administration of ReoPro may result in the formation of human anti-chimeric antibody (HACA) that could potentially cause allergic or hypersensitivity reactions (including anaphylaxis), thrombocytopenia, or diminished benefit upon readministration (see section 4.8, paragraph on Readministration). HACA formation appeared, generally as a low titre, in approximately 5% to 6% of patients after single administrations of ReoPro in Phase III trials (see section 4.8). 

 

Deleted:

 

Readministration of ReoPro to patients undergoing PTCA was assessed in a registry that included 1,342 treatments in 1,286 patients.  Most patients were receiving their second ReoPro exposure; 15% were receiving the third or subsequent exposure.  The overall rate of HACA positivity prior to the readministration was 6% and increased to 27% post-readministration.  There were no reports of serious allergic reactions or anaphylaxis. 

 

Added (bold):

 

Thrombocytopenia was observed at higher rates in the readministration study than in the Phase III studies of first-time administration (see section 4.8), suggesting that readministration may be associated with an increased incidence and severity of thrombocytopenia (see section 4.8, paragraph on Readministration).

 

Renal Disease:

 

Added (bold) Deleted (strikethrough):

 

In the event serious bleeding occurs, platelet transfusion should be considered (see paragraph on Bleeding precautions - Transfusion to restore platelet function). (see ‘Restoration of Platelet Function’).   

 

Added (bold) Deleted (strikethrough):

 

Children or patients older than 80 Yearsor Age Over 80 Years:

 

Deleted:

 

Residues From Manufacture:

 

Trace amounts of papain, resulting from the production process, may be present.

 

4.5           Interactions with other medicinal products and other forms of interaction

 

Added (bold) Deleted (strikethrough):

 

ReoPro has been formally studied as an adjunct to heparin and aspirinacetylsalicylic acid treatment. 

 

Added (bold) Deleted (strikethrough):

 

Although there have been no formal studies of ReoPro with other commonly used cardiovascular drugsmedicinal products, in clinical studies there have been no adverse drug reactions associated with concomitant use of other drugsmedicinal products used in the treatment of angina, myocardial infarction, or hypertension, nor with common intravenous infusion fluids.  These drugsmedicinal products have included warfarin

 

4.6           Pregnancy and lactation

 

Added (bold) Deleted (strikethrough):

 

Animal reproduction studies have not been conducted with ReoPro.  It is also not known whether abciximabReopro can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity.  ReoPro should not be used during pregnancy unless clearly necessary. ReoPro should be given to a pregnant woman only if clearly needed.

 

Breast-feeding of infants should be discontinued in nursingbreast-feeding mothers,

 

4.7           Effects on ability to drive and use machines

 

Added:

 

Not relevant.

 

Deleted:

 

Not applicable.

 

4.8           Undesirable effects

 

Added:

 

The most frequent adverse events are bleeding, back pain, hypotension, nausea, chest pain, vomiting, headache, bradycardia, fever (pyrexia), puncture site pain and thrombocytopenia. Cardiac tamponade, pulmonary (mostly alveolar) haemorrhage and adult respiratory distress syndrome have been reported rarely.

 

The adverse events listed in Table 1 are based on experience from clinical studies. Within the organ system classes, adverse events are listed under headings of frequency using the following categories: common (³1/100 to <1/10); uncommon (³1/1,000 to <1/100); rare (³1/10,000 to <1/1,000).

 

Table 1

Undesirable effects in clinical studies

 

Blood and lymphatic system disorders

 

Common:

Thrombocytopenia

Cardiac disorders

 

Common:

Bradycardia

Rare:

Cardiac tamponade

Gastrointestinal disorders

 

Common:

Nausea, vomiting

General disorders and administration site conditions

 

Common:

Chest pain, pyrexia, puncture site pain

Immune system disorders

 

Rare:

Hypersensitivity/allergic reactions

Musculoskeletal and connective tissue disorders

 

Common:

Back pain

Nervous system disorders

 

Common:

Headache

Respiratory, thoracic and mediastinal disorders

 

Rare:

Adult respiratory distress syndrome

Vascular disorders

 

Common:

Bleeding; hypotension

Uncommon:

Intracranial haemorrhage

Rare:

Pulmonary haemorrhage

 

Bleeding

 

Added (bold) Deleted (strikethrough):

 

In the EPIC trialstudy,

 

1Decrease in haemoglobin >5g/dl.

Major and minor bleeding are defined as follows:

Major bleeding: Decrease in haemoglobin >5 g/dL

Minor bleeding: Spontaneous gross haematuria or haematemesis, or observed blood loss with a haemoglobin decrease >3g/dl or

 

In a subsequent clinical trialstudy, EPILOG, using the heparin regimen, sheath removal and femoral access care guidelines outlined in section 4.4, paragraph on Bleeding precautions, the incidence of major bleeding not associated with CABG surgery in patients treated with ReoPro (1.1%) was not different from patients receiving placebo (1.1%) and there was no significant increase in the incidence of intracranial haemorrhage.  The reduction in major bleeding observed in the EPILOG trialstudy was achieved without loss of efficacy.  Likewise, in the EPISTENT trialstudy, the incidence of major bleeding not associated with CABG surgery in patients receiving ReoPro plus balloon angioplasty (0.6%) or ReoPro with stent placement (0.8%) was not significantly different from patients receiving placebo with stent placement (1.0%).  In the CAPTURE trialstudy, which did not use the low-dose heparin regimen, the incidence of major bleeding not associated with CABG surgery was higher in patients receiving ReoPro (3.8%) than in patients receiving placebo (1.9%).

 

‘Bleeding Precautions: Restoration of Platelet Function’. (see section 4.4, paragraph on Transfusion to restore platelet function).

 

Added:

 

Other vascular disorders

 

The GUSTO V study randomised 16,588 patients with acute myocardial infarction to treatment with combined ReoPro and half-dose reteplase or full dose reteplase alone. The incidence of moderate or severe non-intracranial bleeding was increased in those patients receiving ReoPro and half-dose reteplase versus those receiving reteplase alone (4.6% versus 2.3% respectively).

 

Thrombocytopenia

 

Added (bold) Deleted (strikethrough):

 

Thrombocytopenia has been observed at higher rates following readministration (see paragraph below on Readministration).In a readministration registry study of patients receiving a second or subsequent exposure to ReoPro, the incidence of any degree of thrombocytopenia was 5%, with an incidence of profound thrombocytopenia of 2% (<20,000 cell/ml).  Factors associated with an increased risk of thrombocytopenia were a history of thrombocytopenia on previous ReoPro exposure, readministration within 30 days, and a positive HACA assay prior to the readministration.

 

The most frequent adverse events are back pain, hypotension, nausea, chest pain, vomiting, headache pain, bradycardia, fever, puncture site pain, and thrombocytopenia.  Cardiac tamponade, pulmonary (mostly alveolar) haemorrhage, and adult respiratory distress syndrome have been reported rarely. 

 

Added:

 

Readministration

 

Human antichimeric antibody (HACA) formation appeared, generally as a low titre, in approximately 5% to 6% of patients 2 to 4 weeks after receiving a first exposure to ReoPro in the Phase III clinical studies.

 

Deleted:

 

Human anti-chimeric antibody (HACA) appeared, generally as a low titre, in approximately 5% to 6% of patients 2 to 4 weeks after receiving a first exposure to ReoPro in the Phase III trials.  Hypersensitivity or allergic reactions have been observed rarely following treatment with ReoPro.  Nevertheless, anaphylaxis may potentially occur at any time during administration (see ‘Administration Instructions’).

 

Added:

 

Readministration of ReoPro to patients undergoing PTCA was assessed in a registry that included 1342 treatments in 1286 patients. Most patients were receiving their second ReoPro exposure; 15% were receiving the third or subsequent exposure. The overall rate of HACA positivity prior to the readministration was 6% and increased to 27% post-readministration. There were no reports of serious allergic reactions or anaphylaxis.

 

In a readministration registry study of patients receiving a second or subsequent exposure to ReoPro, the incidence of any degree of thrombocytopenia was 5%, with an incidence of profound thrombocytopenia of 2% (<20,000 cell/mL). Factors associated with an increased risk of thrombocytopenia were a history of thrombocytopenia on previous ReoPro exposure, readministration within 30 days, and a positive HACA assay prior to the readministration.

 

4.9          Overdose

 

Added:

 

There has been no experience of adverse events associated with overdose.

 

However, in the event of acute allergic reactions, thrombocytopenia or uncontrolled bleeding the administration of ReoPro should be immediately discontinued (see section 4.4, paragraphs on Hypersensitivity and Thrombocytopenia). In the event of thrombocytopenia or uncontrolled bleeding, platelet transfusion is recommended (see section 4.4, paragraph on Transfusion to restore platelet function).

 

Deleted:

 

There has been no experience of adverse events associated with overdosage.  However, in the event of acute allergic reactions, thrombocytopenia, or uncontrolled bleeding the administration of ReoPro should be immediately discontinued.  In the event of thrombocytopenia or uncontrolled bleeding, platelet transfusion is recommended.

 

Allergic reactions: See ‘Administration Instructions’.

 

Thrombocytopenia: To evaluate the possibility of thrombocytopenia, platelet counts should be monitored prior to treatment, 2 to 4 hours following the bolus dose of ReoPro, and at 24 hours.  If a patient experiences an acute platelet decrease, additional platelet counts should be determined.  These platelet counts should be drawn in three separate tubes containing ethylenediaminetetraacetic acid (EDTA), citrate, and heparin, respectively, to exclude pseudothrombocytopenia due to in vitro anticoagulant interaction.  If true thrombocytopenia is verified, ReoPro should be immediately discontinued and the condition appropriately monitored and treated.  A daily platelet count should be obtained until it returns to normal.  If a patient’s platelet count drops to 60,000 cells/µl, heparin and aspirin should be discontinued.  If a patient’s platelet count drops below 50,000 cells/µl, platelets should be considered, especially if the patient is bleeding and/or invasive procedures are planned or ongoing. If the patient’s platelet count drops below 20,000 cells/µl, platelets should be transfused.  The decision to use platelet transfusion should be based upon clinical judgment on an individual basis.

 

Uncontrolled bleeding: (Specific guidelines for access site bleeding are given above under ‘Bleeding Precautions: Femoral Artery Access Site’.)  When considering the need to transfuse patients, the patient’s intravascular volume should be assessed.  If hypovolaemic, intravascular volume should be adequately restored with crystalloids.  In asymptomatic patients, normovolaemic anaemia (haemoglobin 7-10g/dl) can be well tolerated; transfusion is not indicated unless a deterioration in vital signs is seen or unless the patient develops signs and symptoms.  In symptomatic patients (eg, syncope, dyspnoea, postural hypotension, tachycardia), crystalloids should be used to replace intravascular volume.  If symptoms persist, the patient should receive transfusions with packed red blood cells or whole blood on a unit-by-unit basis to relieve symptoms; one unit may be sufficient.  Transfusion of donor platelets has been shown to restore platelet function following ReoPro administration in animal studies, and transfusions of fresh random donor platelets have been given empirically to restore platelet function in humans.  In the event of serious uncontrolled bleeding or the need for emergency surgery, ReoPro should be discontinued.  In the majority of patients, bleeding time returns to normal within 12 hours.  If bleeding time remains prolonged and/or there is a marked inhibition of platelet function and/or if rapid haemostasis is required and/or in case(s) where haemostasis is not adequately restored, consideration should be given to seeking advice of a haematologist experienced in the diagnosis and management of bleeding disorders.

 

If rapid haemostasis is required, therapeutic doses of platelets may be administered (at least 5.5 x 1011 platelets).  Redistribution of ReoPro from endogenous platelet receptors to platelets, which have been transfused, may take place.  A single transfusion may be sufficient to reduce receptor blockade to 60% to 70%, at which level platelet function is restored.  Repeat platelet transfusions may be required to maintain haemostasis.

 

 

 

5.             PHARMACOLOGICAL PROPERTIES

 

5.1          Pharmacodynamic properties

 

Added:

 

Pharmacotherapeutic group: Platelet aggregation inhibitors excl. heparin, ATC code: B01A C13.

 

Added (bold) Deleted (strikethrough):

 

ReoPro also binds to the vitronectin (avß3) receptor (avß3) found on platelets and endothelial cells. 

 

Added:

 

Clinical efficacy

 

 

 

6.             PHARMACEUTICAL PARTICULARS

 

6.4           Incompatibilities

 

Added:

 

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

 

Deleted:

 

No incompatibilities have been shown with intravenous infusion fluids or commonly used cardiovascular drugs.  Nevertheless, it is recommended that ReoPro be administered in a separate intravenous line whenever possible and not mixed with other medications.

 

No incompatibilities have been observed with glass bottles or polyvinyl chloride bags or administration sets.

 

6.3          Shelf-life

 

Added (bold) Deleted (strikethrough):

 

Three3 years.

 

Chemical and physical in-use stability has been demonstrated for 24 hours at room temperature 25°C.

 

6.4           Special precautions for storage

 

Added (bold) Deleted (strikethrough):

 

Store in a refrigerator (2°C – 8°C).at 2°C to 8°C (in a refrigerator). 

 

Added:

 

For storage conditions of the diluted medicinal product, see section 6.3.

 

6.5          Nature and contents of container

 

Added (bold) Deleted (strikethrough):

 

ReoPro is supplied as a 5 mL solution in a type I borosilicate glass vial with a Teflon-coated rubber stopper and an aluminium crimp protected by a plastic cap in a pack size of one.

Five ml solution in a Type I borosilicate glass vial with a Teflon-coated rubber stopper and an aluminium crimp protected by a plastic cap, in a pack size of one.

 

6.6           Special precautions for disposal and other handlingInstructions for use and handling

 

Added (bold) Deleted (strikethrough):

 

Preparation of IV infusion: Withdraw the necessary amount of ReoPro for the continuous infusion into a syringe.  Inject into an appropriate container of sterile sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose solution0.9% saline or 5% dextrose and infuse at the calculated rate via a continuous infusion pump.

 

Added:

 

4.       No incompatibilities have been shown with intravenous infusion fluids or commonly used cardiovascular medicinal products. Nevertheless, it is recommended that ReoPro be administered in a separate intravenous line whenever possible and not mixed with other medicinal products.

5.       No incompatibilities have been observed with glass bottles or polyvinyl chloride bags or administration sets.

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

 

 

 

8.             MARKETING AUTHORISATION NUMBERS

 

Updated Irish number format:

 

PA 0502/003/001 (RoI)

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date:

 

31 August 2007 (UK)

17 October2007 (RoI)

Updated on 23/12/2005 and displayed until 07/08/2009
Reasons for adding or updating:
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 6.1 - List of excipients
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text
Updated on 23/12/2004 and displayed until 23/12/2005
Reasons for adding or updating:
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text
Updated on 05/06/2003 and displayed until 23/12/2004
Reasons for adding or updating:
  • New SPC for medicines.ie

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