Eptifibatide
Systematic (IUPAC) name
N 6 -(aminoiminomethyl)-N 2 -(3-mercapto-1-oxopropyl-L-lysylglycyl-L-a-aspartyl-L- tryptophyl-L -prolyl-L-cysteinamide
Identifiers
CAS number	188627-80-7
ATC code	B01AC16
PubChem	123610
DrugBank	BTD00063
Chemical data
Formula	C35H49N11O9S2
Mol. mass	831.96 g/mol
Pharmacokinetic data
Bioavailability	n/a
Protein binding	~25%
Metabolism	?
Half life	~2.5 hours
Excretion	Renal
Therapeutic considerations
Licence data	EU US Image File history File links No higher resolution available. ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules. ... The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ... A chemical formula (also called molecular formula) is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... General Name, Symbol, Number carbon, C, 6 Chemical series nonmetals Group, Period, Block 14, 2, p Appearance black (graphite) colorless (diamond) Atomic mass 12. ... This article is about the chemistry of hydrogen. ... General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless gas Atomic mass 14. ... General Name, Symbol, Number oxygen, O, 8 Chemical series Nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Atomic mass 15. ... General Name, Symbol, Number sulfur, S, 16 Chemical series nonmetals Group, Period, Block 16, 3, p Appearance lemon yellow Atomic mass 32. ... The molecular mass (abbreviated MM) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Many drugs are bound to Blood plasma proteins. ... Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... It has been suggested that Effective half-life be merged into this article or section. ... Excretion is the process of eliminating waste products of metabolism and other materials that are of no use. ... It has been suggested that Renal anomalies and Renal plasma threshold be merged into this article or section. ... The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ...
Pregnancy cat.	B(US) The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ... Motto: (Out Of Many, One) (traditional) In God We Trust (1956 to date) Anthem: The Star-Spangled Banner Capital Washington D.C. Largest city New York City None at federal level (English de facto) Government Federal constitutional republic  - President George Walker Bush (R)  - Vice President Dick Cheney (R) Independence from...
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Routes	IV only

Eptifibatide (Integrilin®, Millennium Pharmaceuticals, also co-promoted by Schering-Plough/Essex), is an anti-coagulant that selectively blocks the platelet glycoprotein IIb/IIIa receptor. Eptifibatide is a cyclic heptapeptide derived from a protein found in the venom of the southeastern pygmy rattlesnake (Sistrurus miliarus 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-peptid tirofiban entered the global market. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... Millennium Pharmaceuticals is a biotechnology company based in the Boston,Massachusetts area of the United States of America. ... An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. ... A 250 ml bag of newly collected platelets. ... In medicine, glycoprotein IIb/IIIa, also gpIIb/IIIa, is an integrin found on platelets. ... Half-Life For a quantity subject to exponential decay, the half-life is the time required for the quantity to fall to half of its initial value. ... Abciximab (previously known as c7E3 Fab), distributed by Eli Lilly under the trade name ReoPro®, is a platelet aggregation inhibitor mainly used during and after coronary artery procedures like angioplasty to prevent platelets from sticking together and causing thrombus (blood clot) formation within the coronary artery. ... Tirofiban (INN, trade name Aggrastat®) is an anticoagulant drug. ...

Integrilin® is sold in two strengthes: vials containing 2 mg/ml (20 mg totally) and 0.75 mg/ml (75 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 intervention (PCI). Percutaneous coronary intervention is an invasive cardiologic therapeutic procedure to treat narrowed coronary arteries (artery stenosis). ...

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. Aspirin or acetylsalicylic acid (acetosal) is a drug in the family of salicylates, often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. ... Clopidogrel (IPA: ) is a potent oral antiplatelet agent often used in the treatment of coronary artery disease, peripheral vascular disease, and cerebrovascular disease. ... Heparin is a highly sulfated glycosaminoglycan widely used as an injectable anticoagulant. ...

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

• Thrombocytopenia : The drug is contraindicated in patients with platelet counts of less than 100,000 because no clinial experience exists regarding such patients.
• 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.
• Allergy to eptifibatide and/or other ingredients.
• Severe, uncontrolled hypertension.
• 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.

Thrombocytopenia (or -paenia, or thrombopenia in short) is the presence of relatively few platelets in blood. ... This article deals specifically with IgE-mediated hypersensitivity. ... For other forms of hypertension, see Hypertension (disambiguation). ...

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 effects. Therefore, not all side effects listed as follows may be attributable to eptifibatide treatment alone: An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ...

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 and minute vs. 0.75 µg/kg and minute). 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. Blood from a finger Bleeding is the loss of blood from the body. ... Donating blood Blood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. ... Anemia (AmE) or anaemia (BrE), from the Greek () meaning without blood, refers to a deficiency of red blood cells (RBCs) and/or hemoglobin. ...

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. In physiology and medicine, hypotension refers to an abnormally low blood pressure. ...

Dosage regime

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 and 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 less 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 clopidrogel or heparin 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.

References

• AHFS Database Online
• Arzneimittel Datenbank (in German)
• http://www.pharmazeutische-zeitung.de/index.php?id=352&type=0 (in German)
• http://www.chemsoc.org/chembytes/ezine/1999/berressem_apr99.htm (information on the biological origin of eptifibatide)

See also

• Glycoprotein IIb/IIIa inhibitors