Eptifibatide is an antiplatelet drug which reversibly binds and inhibits glycoprotein IIb/IIIa receptor of platelets. A protein found in the venom of a southeastern pygmy rattlesnake is used to make eptifibatide. The PURSUIT and IMPACT-II account for the indications of eptifibatide by Food and Drug Administration(FDA)as mentioned below:
Non-FDA-labeled indications are:
Rupture of atherosclerotic plaque or injury to vessel wall exposes the subendothelial matrix of the coronary blood vessel to circulating platelets. This event triggers a platelet signaling cascade that leads to the activation of the glycoprotein IIb/IIIa receptor (GpIIb/IIIa). The activation of Gp IIb/IIIa receptors leads to cross-linking of fibrinogen to attach multiple platelets to form a durable secondary platelet plug. The secondary platelet plug is essential for progression and stability of the clot. The glycoprotein IIb/IIIa receptor inhibitors including abciximab, eptifibatide, sibrafiban, and tirofiban, which block the activation of Gp IIb/IIIa receptors ultimately preventing clot formation/progression.
GP IIb/IIIa heterodimer contains a large extracellular region, a transmembrane domain, and a short intracellular cytoplasmic tail. The Gp IIb/IIIa receptor is a calcium and manganese-dependent heterodimer protein consisting of an alpha- and a beta-subunit. The alpha-subunit characterized by three or four divalent Ca or Mn binding domains that are crucial in the GP IIb/IIIa heterodimer. The beta-subunit comprises of disulfide bonds, binding sites including lysine-glycine-aspartic acid (KGD) bindings binding sites or arginine-glycine-aspartic acid (RGD) for attachment of fibrinogen, von Willebrand factor (vWF) and prothrombin. The binding sites of GP IIb/IIIa are hidden as latent and become active on the surface by undergoing a conformational change via inside-out signaling.
The eptifibatide is a natural disintegrin from snake venom and have highly specific binding to the Gp IIb/IIIa receptor because of the structural resemblance of KGD (Lys-Gly-Asp) sequence. Eptifibatide binds to the KGD binding sites on Gp IIb/IIIa receptor and competitively fights against the binding of the receptor with fibrinogen, von Willebrand factor (vWF) and prothrombin. Higher plasma levels of eptifibatide are needed to competitively inhibit the target of over 80% block of KGD binding sites. Eptifibatide can competitively inhibit the KGD (Lys-Gly-Asp) sequence binding site in both active and inactive states. Eptifibatide has a half-life of 2 to 2.5 hrs and cleared by the kidney. The low affinity for direct binding with GP IIb/IIIa is responsible for rapid states. Furthermore, high doses of eptifibatide provide additional antithrombotic benefits by blocking vitronectin binding site, the ligand for alpha-beta in vascular cells, which may offer other antithrombotic benefits.
Eptifibatide is intravenously administered and is available in strengths of 0.75 mg/ml and 2 mg/ml. The dose of eptifibatide is different in patients diagnosed with acute coronary syndrome (ACS) and in patients undergoing percutaneous coronary intervention (PCI). In patients with ACS, it is given immediately after the diagnosis at a loading dose of 180 mcg/kg IV followed by a continuous i.v. infusion of 2 mcg/kg/min. The infusion is continued up to 72 hours. Pre-PCI, eptifibatide is used as a loading dose of 180 mcg/kg IV followed by a continuous infusion of 2 mcg/kg/min with another 180 mcg/kg IV bolus (double bolus regimen) given 10 minutes after the first one. Status post-PCI eptifibatide infusion continued up to 18 hours. Kidney clears eptifibatide; a maintenance dose is cut down to 50% in patients with serum creatinine greater than 2 mg/dL and keeping loading dose same as that of a normal kidney function. Contraindications to eptifibatide in patients with serum creatinine greater than 4 mg/dL or patients requiring hemodialysis.
In ACS, eptifibatide is used along with other medications including alteplase, heparin, metoprolol, nitroglycerin, morphine or furosemide. Eptifibatide is chemically incompatible with furosemide, and thus they should not be administered in the same intravenous line.
The significant side effect of eptifibatide described in the PURSUIT trial was bleeding. In most cases, bleeding was mild and occurred at femoral access sites. There were more red cell transfusions required in the Eptifibatide group compared to placebo to counteract anemia. However, there is increased bleeding following abciximab administration compared to eptifibatide or tirofiban because of rapid reversibility of latter agents.
Thrombocytopenia is another side effect of eptifibatide reported in several case reports. Thrombocytopenia infrequently occurs with Gp IIb/IIIa inhibitors but sometimes may be profound. The risk of thrombocytopenia associated with eptifibatide (0.1 to 0.2%) and tirofiban (0.1-0.3%) is lesser compared to abciximab (0.4-1.1%). Tirofiban induced thrombocytopenia (secondary to eptifibatide) occurs because of the naturally occurring drug-dependent antibodies specific for eptifibatide occupied Gp IIb/IIIa receptor site. It is also clinically relevant to distinguish eptifibatide-induced thrombocytopenia from other etiologies. Pseudothrombocytopenia can be seen using complete blood cell analysis when blood samples are collected in EDTA- containing tubes. The absence of platelet clumping on peripheral smear rules out pseudo-thrombocytopenia. Amongst the Gp IIb/IIIa inhibitors, only abciximab has been reported to have an association with pseudo-thrombocytopenia. Heparin and eptifibatide are administered simultaneously during PCI and in treatment of ACS. In comparison to heparin-induced thrombocytopenia (HIT), eptifibatide usually causes a steep decline in platelet count (less than 30000 cells/ uL). HIT-1 occurs within 1 and 5 days whereas HIT-2 occurs within 4 to 20 days following heparin administration. Thus thrombocytopenia developing within the first day or severe thrombocytopenia favor thrombocytopenia secondary to eptifibatide. Also, the detection of platelet factor-4 (PF-4) assay in HIT can help differentiate it from eptifibatide-induced thrombocytopenia. Eptifibatide can inhibit to new platelets in both active and inactive state. Thrombocytopenia due to eptifibatide responds better after discontinuation of medication, and addition of platelet bag is not helpful if the patient has a high concentration of eptifibatide in plasma. Other side effects reported include hypotension, heart failure, arrhythmias (ventricular fibrillation, atrial fibrillation), hypersensitivity reactions, gastrointestinal, genitourinary or pulmonary alveolar hemorrhage.
The contraindications to using eptifibatide mentioned below:
Eptifibatide is a pregnancy category B drug. It should only be used cautiously in lactating mothers. Also, the drug is not recommended for use in the pediatric population.
Monitor complete blood count (CBC), serum creatinine, and PT/aPTT. In patients undergoing PCI, measure activated clotting time (ACT).
Bleeding at intravenous sites is the most common adverse effect. Simultaneous use of NSAIDs or other antiplatelet drugs and renal insufficiency would increase the risk of bleeding.
There is no specific antidote for eptifibatide toxicity. Eptifibatide should be discontinued when platelet counts are under 50,000 cells/microliter, and a platelet transfusion ordered when platelet counts are less than 20000 cells/microliter, or there is significant bleeding.
Eptifibatide is useful in the treatment of acute coronary syndrome (ACS) and following percutaneous coronary intervention (PCI). Healthcare workers including nurses, pharmacists, and clinicians should be aware that bleeding and thrombocytopenia are major complications following eptifibatide administration and they should work together as a team to identify these complications early to help bring about optimal patient benefit. [Level V] Also, since heparin is used in conjunction with eptifibatide in the treatment of ACS and during PCI, it is imperative to learn how to differentiate heparin-induced thrombocytopenia from eptifibatide-induced thrombocytopenia.
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