Eptifibatide
Encyclopedia
Eptifibatide is an antiplatelet drug
of the glycoprotein IIb/IIIa inhibitor class. Eptifibatide is a cyclic
heptapeptide derived from a protein found in the venom of the southeastern pygmy rattlesnake (Sistrurus miliarius barbouri
). It belongs to the class of the so-called arginin-glycin-aspartat-mimetics and reversibly binds to platelets. Eptifibatide has a short half-life
. The drug is the third inhibitor of GPIIb/IIIa that has found broad acceptance after the specific antibody abciximab and the non-peptide tirofiban
entered the global market.
Integrilin is sold in two strengths, globally: vials containing 2 mg/ml (20 mg totally) and 0.75 mg/ml (75 mg totally). A third size is sold in the US: 100 ml vials containing 2 mg/ml (200 mg totally).
(PCI).
The drug is always applied together with aspirin
or clopidogrel
and (low molecular weight or unfractionated) heparin
. Additionally, the usual supportive treatment consisting of applications of nitrates, beta-blockers, lidocaine, opioid analgesics and/or benzodiazepines should be employeed as indicated. Angiographic evaluation and other intensive diagnostic procedures may be considered a first line task before initiating therapy with eptifibatide.
The drug should exclusively be used in hospitalized patients both because of the serious degree of patients' illness and because of the possible side-effects of eptifibatide.
s. Therefore, not all side effects listed as follows may be attributable to eptifibatide treatment alone:
The major adverse event in the PURSUIT study was severe bleeding
. Bleeding occurred as well at sites of clinical intervention (local sites) as at other sites (systemically) like urogenital bleedings. Sometimes, these events were severe enough to require transfusion
of blood or plasma concentrates to stop bleeding and counteract anemia
. Severe bleedings occurred in 4.4 and 4.7 % of patients respectively depending on the infusion rate (0.5 µg/kg/min vs. 0.75 µg/kg/min). A few cases of death due to severe bleeding events attributable to drug therapy were reported. No cases of hemorrhagic stroke were seen. Thrombocytopenia of unknown origin (allergic reaction?) was also noticed in 0.2 % of patients.
Additionally, hypotension
was seen frequently (6 %). Cardiovascular failure was also frequent (2 %) as were serious arrhythmias (ventricular fibrillation 1.5 %, atrial fibrillation 6 %). Severe allergic (anaphylactic) reactions occurred in almost 0.2 % of patients. These reactions can be life-threatening and may be due to the peptide character of eptifibatide. Other side effects were rare and mild in nature and may not be connected to eptifibatide therapy.
Eptifibatide is one of very many antiplatelet drugshttp://www.healthvalue.net/antiplateletdrugs.html that all have different consequences on the platelet's activity.
), sold by Johnson and Johnson.
Antiplatelet drug
An antiplatelet drug is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation...
of the glycoprotein IIb/IIIa inhibitor class. Eptifibatide is a cyclic
Cyclic compound
In chemistry, a cyclic compound is a compound in which a series of atoms is connected to form a loop or ring.While the vast majority of cyclic compounds are organic, a few inorganic substances form cyclic compounds as well, including sulfur, silanes, phosphanes, phosphoric acid, and triboric acid. ...
heptapeptide derived from a protein found in the venom of the southeastern pygmy rattlesnake (Sistrurus miliarius barbouri
Sistrurus miliarius barbouri
Sistrurus miliarius barbouri is a venomous pitviper subspecies found in the southeastern United States.-Description: Adults grow to between 35.5 and 76 cm in length . In a study that involved 103 males and 80 females, the average length was 53.5 cm. Snellings and Collins reported a specimen...
). It belongs to the class of the so-called arginin-glycin-aspartat-mimetics and reversibly binds to platelets. Eptifibatide has a short half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
. The drug is the third inhibitor of GPIIb/IIIa that has found broad acceptance after the specific antibody abciximab and the non-peptide tirofiban
Tirofiban
Tirofiban is an antiplatelet drug. It belongs to a class of antiplatelet named glycoprotein IIb/IIIa inhibitors...
entered the global market.
Integrilin is sold in two strengths, globally: vials containing 2 mg/ml (20 mg totally) and 0.75 mg/ml (75 mg totally). A third size is sold in the US: 100 ml vials containing 2 mg/ml (200 mg totally).
Indications
Eptifibatide is used to reduce the risk of acute cardiac ischemic events (death and/or myocardial infarction) in patients with unstable angina or non-ST-segment-elevation (e.g., non-Q-wave) myocardial infarction (i.e., non-ST-segment elevation acute coronary syndromes) both in patients who are to receive non surgery (conservative) medical treatment and those undergoing percutaneous coronary interventionPercutaneous coronary intervention
Percutaneous coronary intervention , commonly known as coronary angioplasty or simply angioplasty, is one therapeutic procedure used to treat the stenotic coronary arteries of the heart found in coronary heart disease. These stenotic segments are due to the build up of cholesterol-laden plaques...
(PCI).
The drug is always applied together with aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
or clopidogrel
Clopidogrel
Clopidogrel is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. The drug works by irreversibly...
and (low molecular weight or unfractionated) heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
. Additionally, the usual supportive treatment consisting of applications of nitrates, beta-blockers, lidocaine, opioid analgesics and/or benzodiazepines should be employeed as indicated. Angiographic evaluation and other intensive diagnostic procedures may be considered a first line task before initiating therapy with eptifibatide.
The drug should exclusively be used in hospitalized patients both because of the serious degree of patients' illness and because of the possible side-effects of eptifibatide.
Contraindications and precautions
- ThrombocytopeniaThrombocytopeniaThrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
: The drug is contraindicated in patients with platelet counts of less than 100,000 per μl because no clinical experience exists regarding such patients. - Renal insufficiency : Eptifibatide undergoes renal elimination. In such patients with renal insufficiency where a glycoprotein IIb/IIIa inhibitor is likely to provide benefit, Abciximab (trade name: Reopro) is an alternative medication.
- Current bleeding tendencies or abnormally prolonged coagulation parameters observed within 30 days before starting therapy with eptifibatide is intended.
- Coagulation parameters such as ACT, aPTT, TT, and PT should be followed closely during therapy and afterwards.
- AllergyAllergyAn Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
to eptifibatide and/or other ingredients. - Severe, uncontrolled hypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
. - Pregnancy : No experience exists. Pregnant patients should be treated only when clearly needed.
- Lactation : No human data exists. Breast-feeding should be avoided during treatment in order to prevent damage to the newborn.
- Geriatric patients : No differences in side effects compared with younger patients have been seen. Nevertheless, geriatric patients should be very closely observed for bleeding and other side-effects.
- Pediatric patients : Eptifibatide is not indicated in patients below 18 years of age, because no experience exists.
Side effects
It should be noticed that all patients receiving eptifibatide were seriously ill and most of them were concomitantly treated with other drugs known to have the potential to cause significant side effectAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s. Therefore, not all side effects listed as follows may be attributable to eptifibatide treatment alone:
The major adverse event in the PURSUIT study was severe bleeding
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...
. Bleeding occurred as well at sites of clinical intervention (local sites) as at other sites (systemically) like urogenital bleedings. Sometimes, these events were severe enough to require transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
of blood or plasma concentrates to stop bleeding and counteract anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
. Severe bleedings occurred in 4.4 and 4.7 % of patients respectively depending on the infusion rate (0.5 µg/kg/min vs. 0.75 µg/kg/min). A few cases of death due to severe bleeding events attributable to drug therapy were reported. No cases of hemorrhagic stroke were seen. Thrombocytopenia of unknown origin (allergic reaction?) was also noticed in 0.2 % of patients.
Additionally, hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
was seen frequently (6 %). Cardiovascular failure was also frequent (2 %) as were serious arrhythmias (ventricular fibrillation 1.5 %, atrial fibrillation 6 %). Severe allergic (anaphylactic) reactions occurred in almost 0.2 % of patients. These reactions can be life-threatening and may be due to the peptide character of eptifibatide. Other side effects were rare and mild in nature and may not be connected to eptifibatide therapy.
Dosage regimen
The recommended adult dosage is an i.v. loading dose of 180 µg/kg over 1 to 2 minutes immediately after diagnosis, followed by continuous i.v.-infusion of 2 µg/kg per minute until either hospital discharge or initiation of coronary artery bypass grafting, or for up to 72 hours. At least 4 hours before discharge all local or systemic bleedings should have been controlled and terminated.Study results
Eptifibatide was licensed due to the positive results of the so called PURSUIT study encompassing 10,948 patients. In this study all patients had suffered either unstable angina or a non-ST-segment-elevation myocardial infarction. Significantly fewer patients developed a myocardial infarction under therapy with eptifibatide. Death rates showed a tendency in favour of eptifibatide, but this superiority was not statistically significant.Additional information
Sometimes the treating physicians require the patient after discharge from hospital to continue treatment with aspirin or clopidogrel for a few weeks, some months or even for life (as usually is the case with aspirin) to prevent recurrence of symptoms, development of myocardial infarction and/or death related to cardiovascular disease. These advises should be adhered to strictly.Eptifibatide is one of very many antiplatelet drugshttp://www.healthvalue.net/antiplateletdrugs.html that all have different consequences on the platelet's activity.
Inventors
Integrilin was invented by Robert M. Scarborough http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2006/08/01/BAGFLK8UD41.DTL and David Phillips, at COR Therapeutics, Inc. in South San Francisco, CA. The company was acquired by Millennium pharmaceuticals,Inc,. of MA in 2001. David Phillips is also the original discoverer of GPIIb/IIIa on the platelets (http://www.neurology.org/cgi/content/abstract/57/suppl_2/S12). Robert Scarborough, a medicinal chemist, is also the discoverer of Natrecor (NesiritideNesiritide
Nesiritide is the recombinant form of the 32 amino acid human B-type natriuretic peptide, which is normally produced by the ventricular myocardium...
), sold by Johnson and Johnson.