Eptifibatide
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Eptifibatide
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| 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. weight | 831.96 g/mol |
| Pharmacokinetic data | |
| Bioavailability | n/a |
| Protein binding | ~25% |
| Metabolism | ? |
| Half life | ~2.5 hours |
| Excretion | Renal |
| Therapeutic considerations | |
| Licence data | |
| Pregnancy cat. |
B(US) |
| Legal status |
℞ Prescription only |
| 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.
Integrilin® is sold in two strengthes: vials containing 2 mg/ml (20 mg totally) and 0.75 mg/ml (75 mg totally).
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[edit] 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).
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.
[edit] 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.
[edit] 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:
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.
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.
[edit] 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.
[edit] 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.
[edit] Additional information
Sometimes the treating physicians require the patient after discharge from hospital to continue treatment with sspirin 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.
[edit] 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)
