Eptifibatide

Eptifibatide is a Glycoprotein IIb/IIIa Inhibitor belonging to the antiplatelet agent.

Eptifibatide is a peptide-based antagonist for glycoprotein IIb/IIIa used in the medical management of myocardial infarction and as an adjunct to percutaneous coronary intervention.

The volume of distribution of Eptifibatide is about 185-260 mL/kg. The Plasma protein binding is approximately 25%. It is cleared from the plasma largely by renal excretion with most of the drug excreted in the urine as eptifibatide. Half-life is about 2.5 hours.

Eptifibatide shows common side effects like Blurred vision, constipation, dizziness when getting up suddenly from a sitting position, headache, unusual tiredness or weakness, pinpoint red spots on the skin, abdominal pain, and discomfort, back pain, bleeding from the bladder, blood in urine, bloody or tarry stools, presence of blood in cough, heavy menstrual bleeding, paralysis, unusual bleeding or bruising, difficulty in swallowing, fast/irregular heartbeat, severe skin rash, and hives, puffing or swelling of eyelids, slurred speech, Inability to move the arms, legs, or facial muscle.

Eptifibatide is available in the form of an Injectable Solution.

Eptifibatide is available in India, the US, the UK, Canada, Singapore, Malaysia, Italy, China, and Australia.

Eptifibatide belonging to the Antiplatelet agent acts as a Glycoprotein IIb/IIIa Inhibitor.

Eptifibatide inhibits platelet aggregation by reversibly binding to the platelet receptor glycoprotein (GP) IIb/IIIa of human platelets, thus preventing the binding of fibrinogen, von Willebrand factor, and other adhesive ligands. Inhibition of platelet aggregation occurs in a dose- and concentration-dependent manner.

The Onset of action of Eptifibatide is found to be immediately following an intravenous administration.

The Duration of Action of Eptifibatide is approximately 4-8 hours.

Eptifibatide is available in the form Injectable solution.

Eptifibatide injectable solution is given via the Intravenous route.

Eptifibatide is used to decrease the risks of major and life-threatening events or new episodes of heart attacks in patients suffering from acute coronary syndrome (ACS). Acute coronary syndrome (ACS) is caused by a sudden reduction or blockage of blood flow to the heart, causing chest pain and heart attacks. This medicine is used in patients who are to be managed medically. It is also used for the reduction of life-threatening adverse events in patients undergoing percutaneous coronary intervention or stent placement procedures.

Eptifibatide is a Glycoprotein IIb/IIIa Inhibitor belonging to the antiplatelet agent.

Eptifibatide is an anti-coagulant that selectively and reversibly blocks the platelet glycoprotein IIb/IIIa receptor.

Eptifibatide is approved for use in the following clinical indications:

• Acute Coronary Syndrome (ACS)

Eptifibatide is indicated to decrease the rate of a combined endpoint of death or new myocardial infarction (MI) in patients with ACS (unstable angina [UA]/non-ST-elevation myocardial infarction [NSTEMI]), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (PCI).

• Percutaneous Coronary Intervention (PCI)

Eptifibatide is indicated to decrease the rate of a combined endpoint of death, new MI, or need for urgent intervention in patients undergoing PCI, including those undergoing intracoronary stenting.

• Acute Coronary Syndrome (ACS)
• Non-ST elevation acute coronary syndromes

IV: Bolus of 180 mcg/kg (maximum: 22.6 mg) beginning after diagnostic coronary angiography, just before PCI, followed by a continuous infusion of 2 mcg/kg/minute (maximum: 15 mg/hour); the second bolus of 180 mcg/kg (maximum: 22.6 mg) should be administered 10 minutes after the first bolus; continue infusion for up to 18 to 24 hours after PCI.

• ST-elevation myocardial infarction (off-label use)

IV: Bolus of 180 mcg/kg (maximum: 22.6 mg) beginning after diagnostic coronary angiography, just before PCI, followed by a continuous infusion of 2 mcg/kg/minute (maximum: 15 mg/hour); the second bolus of 180 mcg/kg (maximum: 22.6 mg) should be administered 10 minutes after the first bolus; continue infusion for up to 18 to 24 hours after PCI.

• Percutaneous Coronary Intervention

Initial: 180 mcg/kg intravenous bolus administered immediately before the initiation of PCI followed by a continuous infusion of 2 mcg/kg/min and a second 180 mcg/kg bolus 10 minutes after the first bolus. Intake should be continued until hospital discharge, or for up to 18 to 24 hours, whichever comes first. The manufacturer recommends a minimum of 12 hours of infusion. Alternatively, an infusion duration of 16 hours may be appropriate as noted in the ESPRIT sub-study.

Eptifibatide is available in various strengths as 0.75 mg/mL and 2 mg/mL.

Avoid herbs and supplements with anticoagulant/antiplatelet activity. The use of anticoagulant/antiplatelet herbs with Eptifibatide may increase the risk of bleeding. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo Biloba.

Eptifibatide is contraindicated in patients with

● Allergy

This medicine is not recommended for use in patients with a known allergy to eptifibatide or any other inactive ingredients present along with it.

● Bleeding disorder

This medicine is not recommended for patients with a history of bleeding disorders due to blood coagulation issues (bleeding diathesis) or active abnormal bleeding within the previous 30 days due to the increased risk of worsening the patient’s condition.

● Severe hypertension

This medicine is not recommended for use in patients suffering from severe hypertension (high blood pressure levels more than 200/110 mm Hg) that is not adequately controlled using appropriate medication due to the increased risk of worsening the patient’s condition.

● Major surgery

This medicine is not recommended for use in patients who have undergone major surgery within the preceding 6 weeks due to the increased risk of worsening the patient’s condition.

● Stroke

This medicine is not recommended for use in patients with a history of stroke within the past 30 days or any record of hemorrhagic stroke (an emergency condition where blood vessels rupture within the brain) due to the increased risk of worsening the patient’s condition.

● GP IIb/IIIa inhibitor

This medicine is not recommended for use in patients receiving or patients about to receive other parenteral GP IIb/IIIa inhibitors since it may worsen the patient's condition.

● Hemodialysis

This medicine is not recommended for use in patients who are undergoing dialysis or have a dependency on this procedure due to the increased risk of worsening the patient’s condition.

• Bleeding

Bleeding is the most common complication encountered during Eptifibatide therapy. Administration of Eptifibatide is associated with an increase in major and minor bleeding, as classified by the criteria of the Thrombolysis in the Myocardial Infarction Study group (TIMI). Most major bleeding associated with Eptifibatide has been at the arterial access site for cardiac catheterization or from the gastrointestinal or genitourinary tract. Minimize the use of arterial and venous punctures, intramuscular injections, and the use of urinary catheters, nasotracheal intubation, and nasogastric tubes. When obtaining intravenous access, avoid non-compressible sites (e.g., subclavian or jugular veins).

• Use of Thrombolytics, Anticoagulants, and Other Antiplatelet Agents

Risk factors for bleeding include older age, a history of bleeding disorders, and concomitant use of drugs that increase the risk of bleeding (thrombolytics, oral anticoagulants, nonsteroidal anti-inflammatory drugs, and P2Y12 inhibitors). Concomitant treatment with other inhibitors of platelet receptor glycoprotein (GP) IIb/IIIa should be avoided. In patients treated with heparin, bleeding can be minimized by close monitoring of the aPTT and ACT.

• Care of the Femoral Artery Access Site in Patients Undergoing Percutaneous Coronary Intervention (PCI)

In patients undergoing PCI, treatment with Eptifibatide is associated with an increase in major and minor bleeding at the site of arterial sheath placement. After PCI, Eptifibatide infusion should be continued until hospital discharge or up to 18 to 24 hours, whichever comes first. Heparin use is discouraged after the PCI procedure. Early sheath removal is encouraged while Eptifibatide is being infused. Prior to removing the sheath, it is recommended that heparin be discontinued for 3 to 4 hours and an aPTT of <45 seconds or ACT <150 seconds be achieved. In any case, both heparin and Eptifibatide should be discontinued, and sheath hemostasis should be achieved at least 2 to 4 hours before hospital discharge. If bleeding at the access site cannot be controlled with pressure, infusion of Eptifibatide and heparin should be discontinued immediately.

• Thrombocytopenia

There have been reports of acute, profound thrombocytopenia (immune-mediated and non-immune mediated) with Eptifibatide. If acute profound thrombocytopenia or a confirmed platelet decreases to <100,000/mm3, discontinue Eptifibatide and heparin (unfractionated or low-molecular-weight). Monitor serial platelet counts, assess the presence of drug-dependent antibodies and treat as appropriate. There has been no clinical experience with Eptifibatide initiated in patients with a baseline platelet count that should be monitored closely.

• Renal impairment

Use caution in patients with renal dysfunction (estimated CrCl <50 mL/minute, using Cockcroft-Gault equation); dosage adjustment is required. Use is contraindicated in patients dependent upon hemodialysis.

It is not known whether eptifibatide is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Eptifibatide is administered to a nursing mother.

Eptifibatide has been assigned to pregnancy category B by the FDA. Animal data have failed to reveal evidence of fetotoxicity after administration of doses equivalent to 4 times the maximum recommended human daily dose. There are no adequate or controlled data from human pregnancy studies. Eptifibatide should only be used during pregnancy when the need has been clearly established.

Avoid herbs and supplements with anticoagulant/antiplatelet activity. The use of anticoagulant/antiplatelet herbs with eptifibatide may increase the risk of bleeding. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo Biloba.

• Common Adverse effects

Hypotension, Thrombocytopenia (1% to 3%; includes acute profound thrombocytopenia, immune-mediated thrombocytopenia), Injection site reaction.

• Rare Adverse effects

Anaphylaxis, cerebrovascular accident, gastrointestinal hemorrhage, intracranial hemorrhage, pulmonary hemorrhage

Eptifibatide may interact with other

• Use Of Thrombolytics, Anticoagulants, And Other Antiplatelet Agents

Coadministration of antiplatelet agents, thrombolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. Concomitant treatment with other inhibitors of platelet receptor GP IIb/IIIa should be avoided.

● Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider the risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.

● Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties.

● Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.

● Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased.

● Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding.

● Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required.

● Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding.

● Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

● Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

● Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

● Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.

● Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

● Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by the concurrent use of these agents.

● Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

● Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider the risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.

● Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result.

The common side effect of Eptifibatide include the following

Common

• Blurred vision, Constipation, Dizziness when getting up suddenly from a sitting position, Headache, Unusual tiredness or weakness, Pinpoint red spots on the skin, Abdominal pain, and discomfort.

Rare

• Back pain, Bleeding from the bladder, Blood in urine, Bloody or tarry stools, Presence of blood in cough, Heavy menstrual bleeding, Paralysis, unusual bleeding or bruising, Difficulty in swallowing, Fast/irregular heartbeat, Severe skin rash, and hives, Puffing or swelling of eyelids, Slurred speech, Inability to move the arms, legs, or facial muscle.

• Pregnancy

Pregnancy Category B.

Teratology studies have been conducted in mice (doses up to 200 mg/kg/day), rats (doses up to 400 mg/kg/day), and rabbits (doses up to 200 mg/kg/day). Doses of 400 mg/kg in rats, 200 mg/kg/day in mice and 100 mg/kg in rabbits produced maternal toxicity, as well as fetal toxicity, but there was no evidence of the teratogenic potential of Eptifibatide. There are, however, no adequate and well-controlled studies on pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

• Nursing Mothers

Studies in rats have shown Eptifibatide is excreted in the milk. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Eptifibatide, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

• Pediatric Use

As per FDA, the safety and effectiveness of Eptifibatide in pediatric patients have not been studied.

• Geriatric Use

The PURSUIT and IMPACT II clinical studies enrolled patients up to the age of 94 years (45% were age 65 and over; 12% were age 75 and older). There was no apparent difference in efficacy between older and younger patients treated with Eptifibatide. The incidence of bleeding complications was higher in the elderly in both placebo and Eptifibatide groups, and the incremental risk of Eptifibatide-associated bleeding was greater in the older patients. No dose adjustment was made for elderly patients, but patients over 75 years of age had to weigh at least 50 kg to be enrolled in the PURSUIT study; no such limitation was stipulated in the ESPRIT study.

There has been only limited experience with the overdosage of Eptifibatide. There were 8 patients in the IMPACT II study, 9 patients in the PURSUIT study, and no patients in the ESPRIT study who received bolus doses and/or infusion doses more than double those called for in the protocols. None of these patients experienced an intracranial bleed or another major bleeding. Eptifibatide was not lethal to rats, rabbits, or monkeys when administered by continuous intravenous infusion for 90 minutes at a total dose of 45 mg/kg (about 2 to 5 times the recommended maximum daily human dose on a body surface area basis). Symptoms of acute toxicity were loss of righting reflex, dyspnea, ptosis, and decreased muscle tone in rabbits and petechial hemorrhages in the femoral and abdominal areas of monkeys.

Management:

From in vitro studies, eptifibatide is not extensively bound to plasma proteins and thus may be cleared from plasma by dialysis.

Pharmacodynamic

Eptifibatide is an anti-coagulant that selectively and reversibly blocks the platelet glycoprotein IIb/IIIa receptor.

Pharmacokinetics

• Absorption

Information is not available.

• Distribution

The volume of distribution of Eptifibatide is about 185-260 mL/kg. The Plasma protein binding is approximately 25%.

• Metabolism and Excretion

It is cleared from the plasma largely by renal excretion with the majority of the drug excreted in the urine as eptifibatide. Half-life is about 2.5 hours.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020718s037lbl.pdf
• https://www.rxlist.com/integrilin-drug.htm#indications
• https://reference.medscape.com/drug/integrilin-eptifibatide-342149
• https://www.mims.com/philippines/drug/info/eptifibatide?mtype=generic
• https://go.drugbank.com/drugs/DB00063
• https://www.drugs.com/mtm/eptifibatide.html#:~:text=Eptifibatide is used to prevent,listed in this medication guide.
• https://www.practo.com/medicine-info/eptifibatide-2241-api
• https://www.uptodate.com/contents/eptifibatide-drug-information#F166038