ReoPro

Class: Platelet-aggregation Inhibitors- Antithrombotic Agents
– Platelet-aggregation Inhibitors
– GP IIb/IIIa Receptor Inhibitors
Chemical name: Human mouse monoclonal C7E3 clone, p7E3VHhCgam anti-human glycoprotein IIb/IIIa immunoglobulin G disulfide containing human mouse monoclonal c7E3 monoclonal chain
Brands: ReoPro

Introduction

ReoPro is a Platelet aggregation inhibitor; a platelet glycoprotein (GP IIb/IIIa)-receptor inhibitor.

Uses for ReoPro

Acute Ischemic Complications of PCI

Adjunct to anticoagulant therapy (e.g., heparin [referring throughout this monograph to unfractionated heparin], low molecular weight heparin), aspirin, and a P2Y12 platelet adenosine diphosphate (ADP)-receptor antagonist (e.g., clopidogrel, prasugrel, ticagrelor) to prevent acute cardiac ischemic complications in patients undergoing PCI or in patients with non-ST-segment-elevation acute coronary syndromes (NSTE ACS; unstable angina or non-ST-segment-elevation MI [NSTEMI]) not responding to conventional medical therapy in whom PCI is planned within 24 hours.¶

A GPI IIb/IIIa receptor inhibitor may reduce the chance of having cardiac ischemic incidents, which include later MI and death in patients suffering from NSTE ACS who undergo PCI as well as patients with such conditions who are undergoing PCI.

The safety and effectiveness of PCI for patients who are not receiving PCI are not confirmed.

It is the American College of Cardiology Foundation (ACCF), AHA, the Society for Cardiovascular Angiography and Interventions (SCAI) as well as other experts don’t recommend the routine usage of GP IIb/IIIa-receptor inhibitors for patients suffering from an elevation in ST-segment STMI (STEMI) who are undergoing PCI However, specific use of this drug as an alternative to heparin could be appropriate for certain patients at high risk (e.g. patients with an anterior MI that is large and/or an excessive thrombus).

ACCF/AHA/SCAI has stated that the administration of a GP IIb/IIIa receptor inhibitor prior to PCI as an addition to heparin could be especially beneficial for patients suffering from NSTE ACS with high-risk characteristics (e.g. high troponin) and do not receive bivalirudin, and who are not treated with Clopidogrel.

Concerning the selection of GP IIb/IIIa receptor inhibitors for patients receiving PCI ReoPro IV “double-bolus” IV eptifibatide and high dose tirofiban administered by injecting directly into the veins, all of them produce an extremely high level of platelet inhibition and can decrease the risk of ischemic complications.

Non-ST-Segment-Elevation Acute Coronary Syndromes

It has been prescribed to patients suffering from unsteady angina and NSTEMI (i.e., NSTE ACS) treated with conservative medical treatment. However, the doctors and the manufacturer have stated that the safety and effectiveness of ReoPro have not been established in patients not taking PCI.

A GP IIb/IIIa receptor inhibitor could be utilized together with aspirin prior to angiography diagnostics (“upstream”) for patients suffering from NSTE ACS for whom the initial treatment with invasive procedures is in the works. However, IV tirofiban or eptifibatide is the most commonly used GP IIb/IIIa inhibitor in this application. ReoPro should be considered in this scenario only when there is no significant delay prior to angiography or PCI is expected to be conducted.

ReoPro Dosage and Administration

General

• Stop infusions for patients whose PCI has not worked.

Adjunctive Antithrombotic Therapy: General Considerations

• Aspirin is used in conjunction with heparin during clinical research.
• Dosage of heparin needed to ensure an adequate activated clotting rate (ACT) when combined treatment with ReoPro could be lower than monotherapy with heparin. (See Specific Drugs under Interactions.)

Adjunctive Antithrombotic Therapy When Used to Prevent Acute Ischemic Complications of PCI

• Aspirin: Through clinical trials, patients were treated with 325 mg for 2 minutes before PCI and then every day following PCI. ACCF/AHA/SCAI recommends that aspirin of 325 mg be administered prior to PCI for patients who are not receiving aspirin therapy for maintenance. Patients who are already taking maintenance therapy with aspirin must be given a dose of 81-325 mg prior to the procedure.
• P2Y12 receptor antagonist: A loading dose of clopidogrel or prasugrel or ticagrelor is suggested prior to PCI for patients who undergo the procedure of stent placement.
• Heparin sodium in clinical trials, subjects received 70 units/kg of heparin if the baseline ACT 200 seconds or less; Additional injections in the range of 20 units/kg were administered to ensure an ACT that was greater than 200 seconds throughout the process. Experts recommend using lower doses of concurrent IV heparin sodium (e.g. 50-70 units/kg) administered 6 days prior to PCI and targeted towards an ACT of 200 seconds or more. (See the Laboratory Monitoring under the section on Cautions.) Heparin use post procedurally is generally is not recommended.

Administration

IV Administration

For drug and solution compatibility information, refer to the section Compatibility under Stability.

Give IV injections followed by an IV infusion with an instrument for controlled infusion (e.g. pump).

Do not shake the vial.

Filter injection following dilution prior to administration of IV or during infusion, using a sterile nonpyrogenic, low protein-binding filter (0.2 or 5 millimeters).

In the case of IV injections, inject an appropriate amount from the syringe, and inject the filter prior to administering.

Throw away any portion that is not used.

Do not mix or administer other medications on the same vein as ReoPro infusion or injection.

Dilution

To administer IV infusions, take the sufficient dose from the syringe and inject it into a suitable container of 0.9%sodium  chloride or 5 % dextrose injection.

Rate of Administration

To administer IV injections, spread the injection for a minimum of 1 minute.

Dosage

Adults

Acute Ischemic Complications of PCI

IV

Patients who are undergoing PCI: 0.25 mg/kg by IV injection between 10 and 60 minutes before PCI and then followed by an Infusion IV of 0.125 mg/kg per minute (maximum of 10 mg/min) throughout 12 hours.

Patients who are scheduled to undergo PCI in less than 24 hours 0.25 mg/kg are administered via intravenous injection. This is followed by an intravenous infusion of 10 mg/min for 18-24 hours, ending 1 hour after the procedure.

Prescribing Limits

Adults

Acute Ischemic Complications of PCI

IV

Patients who undergo PCI 10 mg/minute maximum (as Infusion IV) throughout 12 hours.

Special Populations

No specific dosage recommendations for populations currently.

Cautions for ReoPro

Contraindications

• Diathesis bleeding or active internal bleeding or recently (within six weeks) clinically significant GI or Genitourinary bleeding.
• Uncontrolled hypertension is severe.
• Recent (within six weeks) major operation or trauma.
• A history of cerebrovascular accident (CVA) within the preceding two years or CVA with significant residual neurologic impairment.
• Recent (within the last seven days) treatment with oral anticoagulants, unless the prothrombin duration (PT) exceeds <=1.2 times the control value.
• Thrombocytopenia (platelet count <100,000/mm³).
• Intracranial neoplasm.
• Aneurysms or arteriovenous malformations.
• Utilization for IV dextran before and during PCI.
• A presumptive or confirmed evidence of vasculitis.
• There is a history of hypersensitivity towards any component in the formula, or to proteins from murine.

Warnings/Precautions

Warnings

Hematologic Effects

The risk for significant bleeding (e.g. intracranial hemorrhage, genitourinary or GI  bleeding, bleeding from the arterial access sites), as well as smaller bleeding (e.g. the spontaneous gross hematuria, bleeding due to hematemesis) and may, need blood transfusions or platelet transfusions. (See Bleeding Warnings and Laboratory Monitoring under the heading Cautions.)

Rarely, there is a report of pulmonary alveolar hemorrhage.

A higher risk of major bleeding is seen in patients who weigh <=75 kg; during concomitant thrombolytic therapy; when PCI is performed within 12 hours of the onset of symptoms of MI; following prolonged (>70 mins) PCI; or following unsuccessful PCI.

If bleeding isn’t managed by pressure, stop abciximab immediately and heparin with it.

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis could be a possibility. If anaphylaxis is observed, stop ReoPro right away and immediately begin treatment. Drugs for the treatments of allergic reactions (e.g. Epinephrine, epinephrine dopamine, theophylline and corticosteroids, antihistamines) must be available immediately.

Human antichimeric antibodies (HACA) has been reported. There is a possibility of hypersensitivity reactions (including anaphylaxis) as well as thrombocytopenia or decreased antithrombotic effect when ReoPro has been administered in the past or monoclonal antibodies were administered to patients suffering from HACA levels.

General Precautions

Bleeding Precautions

To decrease the bleeding risk be sure to follow strict anticoagulation guidelines. Use the short course of low dose, weight-adjusted, heparin. Beware of any trauma to the vascular system or other types and be sure to control the vascular (e.g. Femoral arterial) access points and observe all possible bleeding areas during and following treatment.

Take care when placing, maintenance, and removal of the vascular access sheaths. Avoid the femoral vein sheaths installation. When inserting sheaths to puncture only the anterior wall of the femoral artery and avoid Seldinger (through or via) technique. Take the necessary precautions when the sheath is in position (e.g. the complete bed rest, elevating the head to 30deg, restraining the limb into which sheath has been being inserted, regular checking of the vascular access point and distal pulses in the limb affected).

After PCI discontinue heparin right away and remove arterial sheath within 6 hours after PCI (at minimum 2 hours following the discontinuation of the heparin) If aPTT is less than 50 seconds or ACT 175 seconds. After sheath removal applies pressure to the femoral arterial system for at least 30 minutes in order to attain hemostasis. Monitor and measure hematomas to determine the possibility of enlargement.

To prevent injuries to the vascular system reduce punctures for venous or arterial blood, IM injections, cutdown locations, and the using nasotracheal tubes and nasogastric tubes, urinary catheters and automated BP Cuffs; beware of setting up IV access in noncompressible locations (e.g. subclavian, subclavian, or Jugular veins) Consider using an implanted venipuncture system (e.g. the heparin lock) to draw blood. note and track the sites of vascular puncture and cutdown sites; remove dressings carefully and gently.

If surgery for an emergency is required then stop ReoPro.

Thrombocytopenia

The risk of developing thrombocytopenia. Severe thrombocytopenia (platelet count less than 20,000/mm ^3.) has been reported more frequently than when using tirofiban.

Check platelet count prior to treatment, at least 2-4 hours following the first IV injection and 24 hours after the initiation of therapy or prior discharge, whichever comes first. Consider the possibility of pseudo thrombocytopenia or heparin-induced thrombocytopenia (in patients receiving concomitant heparin therapy). Exclude pseudo thrombocytopenia caused by an in vitro anticoagulant interaction by sampling blood in tubes containing edetate disodium (EDTA), citrate, or heparin. A low platelet count in the presence of EDTA but not in the presence of heparin and/or citrate supports a diagnosis of pseudo thrombocytopenia.

If thrombocytopenia can be confirmed as true then stop ReoPro and start the appropriate treatment and follow-up. Transfusions of platelets may help improve the function of platelets.

Potentially increased rate as well as severity upon the administration.

It is not recommended in people with platelet counts of 100,000/mm ^3..

Laboratory Monitoring

Prior to administration, gather platelet count as well as PT, ACT and APTT.

Check platelet count before or after therapy. (See Thrombocytopenia under Cautions.)

When ReoPro starts 18-24 hours before PCI keep aPTT at 60-85 seconds. During PCI ensure ACT at a rate of 200 seconds or more. If anticoagulation is maintained after PCI keep aPTT at 55 and 75 seconds.

Check aPTT or ACT prior to arterial sheath removal. don’t remove sheath until APTT is less than 50 seconds, or ACT is between 150 and 180 minutes (approximately 6 hours following PCI).

Specific Populations

Pregnancy

Category C.

Lactation

It is not known if ReoPro can be dispersed into milk. Take care when using this medication.

Pediatric Use

It is not known if it is safe and effective in children younger than 18 years age.

Geriatric Use

There aren’t any significant differences in quality and safety for patients aged 65-74 in comparison to older adults. There is not enough experience with patients over 75 years old to establish whether they respond differently than younger adults.

Common Adverse Effects

Back pain, bleeding, nausea, hypotension vomiting, chest pain headache, bradycardia abdominal pain and peripheral edema.

Interactions for ReoPro

No studies of the interaction between drugs have been conducted until now.

Specific Drugs

Drug	Interaction	Comments
Anticoagulants, oral	Increased risk of bleeding	Be aware
Dextran	Higher risk of bleeding	The use of the same medication is not recommended.
Dipyridamole	Increased risk of bleeding	Be aware
Heparin	Risk of bleeding increases	Watch for aPTT as well ACT during therapy
NSAIAs	The risk of bleeding is increased	Make sure to use caution
Thrombolytics (e.g. Retplase)	Risk of major bleeding increases	Consider the risk versus the anticipated benefits of treatment that may be administered concurrently.
Ticlopidine	Increased risk of bleeding	Make sure to use caution

Advice to Patients

• Risk of bleeding serious or hemorrhage.
• Important importance of monitoring close to the lab.
• The importance of informing doctors about the current or upcoming therapy which includes prescription and OTC medications and herbal or dietary supplements, in addition to any concomitant illness.
• It is important for women to inform their healthcare providers when they are planning to become pregnant, or plan to breastfeed.
• The importance of informing patients about other important information regarding precautions.