Eptifibatide is an intravenous platelet aggregation inhibitor indicated for the treatment of patients undergoing percutaneous coronary intervention (PCI), including intracoronary stenting, and acute coronary syndromes managed medically or with PCI. Eptifibatide is a cyclic peptide platelet glycoprotein IIb/IIIa inhibitor. Eptifibatide contains 6 amino acids and a mercaptopropionyl residue. Cyclic peptides are more resistant to degradation than linear peptides, but still have short half-lives because they are broken down in the body. Eptifibatide has a shorter half-life than abciximab, and its effects on circulating platelets wear off more quickly. Bleeding and hypotension are the most common adverse reactions reported with eptifibatide use. Preclinical and clinical studies indicate that eptifibatide is not immunogenic, most likely because of its low molecular weight.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Storage: Vials may be stored at controlled room temperature for up to 2 months. Protect from light.
Intravenous Administration
IV bolus
-Withdraw the bolus dose from the 10 mL vial into a syringe.
-Administer undiluted by IV push.
Continuous IV infusion
-Initiate the continuous infusion immediately after the bolus dose.
-When using an IV infusion pump, administer eptifibatide undiluted directly from the 100mL vial. Spike the vial with a vented infusion set.
Bleeding is the most common complication associated with eptifibatide. Major bleeding, defined as intracranial hemorrhage or a decrease in hemoglobin (Hgb) more than 5 g/dL, occurred in 1.3% to 10.8% in eptifibatide-treated patients and 0.4% to 9.3% of placebo-treated patients during clinical trials. Minor bleeding, including spontaneous gross hematuria, spontaneous hematemesis, and observed blood loss with a Hgb decrease of 3 to 4 g/dL, occurred in 3% to 13.1% in eptifibatide-treated patients and 2% to 7.6% of placebo-treated patients. Overall incidence of major bleeding was greater in patients undergoing CABG surgery. Risk of bleeding increased as patient weight decreased. Most major bleeding associated with eptifibatide has been at the arterial access site for cardiac catheterization or from the gastrointestinal (GI bleeding) or genitourinary tract; oropharyngeal/gingival and retroperitoneal bleeding were also reported. In patients undergoing percutaneous coronary intervention (PCI), eptifibatide treatment is associated with an increase in major and minor bleeding at the site of arterial sheath placement. Cerebral, gastrointestinal, and pulmonary hemorrhage have been reported during postmarketing use with eptifibatide. Fatal bleeding has been reported. 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). Discontinue eptifibatide and heparin immediately if bleeding at access site cannot be controlled with pressure.
The overall incidence of hemorrhagic stroke was 0.5% to 0.7% for eptifibatide-treated patients and 0.7% to 0.8% for patients given placebo during clinical trials. Intracranial bleeding was rare. A single case of cerebral infarction was reported. Cerebral bleeding has been reported during postmarketing experience.
There have been reports of acute, profound thrombocytopenia (non-immune and immune-mediated) with eptifibatide. Discontinue eptifibatide and concomitant heparin in the event of profound thrombocytopenia or a confirmed platelet decrease to less than 100,000/mm3. Monitor serial platelet counts, assess for the presence of drug-dependent antibodies, and treat as appropriate. In the PURSUIT and IMPACT II studies, the incidence of thrombocytopenia (platelet count less than 100,000/mm3 or 50% or more reduction from baseline) and the incidence of platelet transfusions were similar between patients treated with eptifibatide and placebo. In the ESPRIT study, the incidence of thrombocytopenia was 1.2% in the eptifibatide group and 0.6% in the placebo group. Acute profound thrombocytopenia and immune-mediated thrombocytopenia have also been reported during postmarketing experience with eptifibatide.
Anaphylaxis/anaphylactoid reactions and urticaria have been reported with eptifibatide use.
Hypotension (7%) was the only serious non-bleeding adverse reaction that occurred at a rate of at least 1% and was more common with eptifibatide than placebo (6%) during clinical trials.
The potential for antibody formation to eptifibatide has been studied in 433 patients. Eptifibatide was non-antigenic in 412 patients receiving a single dose (135 mcg/kg bolus followed by an infusion of either 0.5 mcg/kg/minute or 0.75 mcg/kg/minute) and in 21 patients who received 2 doses (135 mcg/kg bolus followed by a continuous infusion of 0.75 mcg/kg/minute) 28 days apart. In both cases, plasma for antibody detection was collected approximately 30 days after each dose. The development of antibodies at higher doses has not been established. There have been reports of immune-mediated thrombocytopenia with postmarketing experience. IgG antibodies that react with the glycoprotein IIb/IIIa complex were identified in the presence of eptifibatide and in eptifibatide-naive patients. These findings suggest that acute thrombocytopenia can develop as a result of naturally occurring drug-dependent antibodies or those induced by prior exposure to eptifibatide. Similar antibodies were noted with other glycoprotein IIb/IIIa agents.
Eptifibatide is contraindicated in patients with a hypersensitivity to the drug or any component of the product.
Eptifibatide is contraindicated in patients with bleeding diathesis (coagulopathy) or evidence of active abnormal bleeding within the previous 30 days, severe uncontrolled hypertension (blood pressure more than 200/110 mmHg), major surgery within the previous 6 weeks, and history of stroke within 30 days or any history of hemorrhagic stroke. Minimize the use of arterial puncture and venipuncture, intramuscular injections, and the use of urinary catheters, nasotracheal intubation, and nasogastric tubes. Avoid non-compressible sites (e.g., subclavian or jugular veins) when obtaining intravenous access. Most major bleeding associated with eptifibatide has been at the arterial access site for cardiac catheterization or from the gastrointestinal or genitourinary tract. In patients undergoing percutaneous coronary intervention (PCI), eptifibatide treatment is associated with bleeding at the site of arterial sheath placement. Discontinue eptifibatide and heparin immediately if bleeding at the access site cannot be controlled with pressure. Heparin use is discouraged after the PCI procedure. Early sheath removal is encouraged while eptifibatide is being infused. Before sheath removal, ensure heparin has been discontinued for 3 to 4 hours and aPTT is less than 45 seconds or ACT is less than 150 seconds. Ensure both heparin and eptifibatide are discontinued and sheath hemostasis is achieved at least 2 to 4 hours before hospital discharge.
Eptifibatide is contraindicated in dialysis-dependent patients with renal failure; the safety and efficacy of eptifibatide in dialysis-dependent patients has not been established. Drug clearance is decreased and plasma concentrations are doubled in patients with renal impairment (CrCl less than 50 mL/minute); dosage reduction of the continuous infusion is required.
Bleeding complications were higher in elderly patients in both integrelin and placebo groups during clinical trials, and the incremental risk of eptifibatide-associated bleeding was greater in geriatric patients.
Monitor platelet counts closely in patients with low platelet counts. Discontinue eptifibatide and concomitant heparin in the event of profound thrombocytopenia or a confirmed platelet decrease to less than 100,000/mm3. Monitor serial platelet counts, assess for the presence of drug-dependent antibodies, and treat as appropriate.
Available data on the use of eptifibatide during human pregnancy are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Myocardial infarction is a medical emergency in pregnancy which can be fatal to the pregnant woman and fetus if left untreated; do not withhold eptifibatide therapy for a pregnant woman because of potential concerns regarding the effects to the fetus. Eptifibatide use in pregnancy has been described in limited case reports. A 31-year-old pregnant woman at 37 weeks gestation received eptifibatide for 7 days for the peripartum management of her dual antiplatelet therapy after bare metal stent insertion for acute myocardial infarction at 32 weeks gestation. Eptifibatide was discontinued at labor induction, and epidural anesthesia was initiated 12 hours after stopping eptifibatide. The patient had an uneventful vaginal delivery after 12 hours of neuraxial analgesia, and the estimated blood loss was 500 mL. In another case, eptifibatide was used in a 44-year-old pregnant woman at 8 weeks gestation with intracoronary stent placement for acute myocardial infarction. She received eptifibatide for 24 hours before being transitioned to clopidogrel and aspirin. At 36 weeks gestation, the woman delivered a healthy infant via uneventful caesarian section. In animal reproduction studies, there was no evidence of adverse developmental effects when eptifibatide was administered to pregnant rats and rabbits at approximately 4 times the recommended maximum daily human dose.
There are no available data on the presence of eptifibatide in human milk, the effects on the breast-fed infant, or the effects on milk production. Eptifibatide is a peptide, and it is likely to be destroyed in the breast-feeding infant's gastrointestinal tract and not absorbed orally by the breast-fed infant.
For the adjunctive treatment of patients undergoing percutaneous coronary intervention (PCI), including those undergoing coronary stenting, to prevent cardiac ischemic complications (e.g., myocardial infarction prophylaxis):
Intravenous dosage:
Adults: 180 mcg/kg (Max: 22.6 mg) IV bolus, followed by 2 mcg/kg/minute continuous IV infusion. Max: 15 mg/hour. Administer a second 180 mcg/kg IV bolus 10 minutes after the first bolus. Continue the infusion until hospital discharge, or for up to 18 to 24 hours, whichever comes first. A minimum of 12 hours of therapy is recommended. Give concomitantly with aspirin and heparin. Administer aspirin 160 to 325 mg PO at 1 to 24 hours prior to PCI and daily thereafter. Dose heparin to maintain a target ACT of 200 to 300 seconds. Administer a heparin 60 unit/kg IV bolus initially in patients not treated with heparin within 6 hours prior to PCI; additional boluses may be administered during PCI to maintain target ACT. Do not administer heparin after PCI. Discontinue eptifibatide in patients who require thrombolytic therapy. Discontinue eptifibatide at least 2 to 4 hours prior to CABG surgery.
For the treatment of non-ST elevation acute coronary syndromes, including acute myocardial infarction, NSTEMI and unstable angina, managed medically or with percutaneous coronary intervention (PCI):
Intravenous dosage:
Adults: 180 mcg/kg (Max: 22.6 mg) IV bolus, followed by 2 mcg/kg/minute (Max: 15 mg/hour) continuous IV infusion until hospital discharge or initiation of CABG surgery up to 72 hours or until hospital discharge or 18 to 24 hours after PCI, whichever is earlier, allowing for up to 96 hours of therapy. Administer an additional 180 mcg/kg IV bolus 10 minutes after the first bolus in persons undergoing PCI. Administer concomitantly with aspirin and heparin. During medical management, dose heparin to maintain a target aPTT of 50 to 70 seconds. If weight 70 kg or more, administer heparin 5,000 units IV bolus followed by 1,000 units/hour continuous IV infusion. If weight less than 70 kg, administer heparin 60 unit/kg IV bolus followed by 12 units/kg/hour continuous IV infusion. During PCI, dose heparin to maintain a target ACT of 200 to 300 seconds. If heparin is initiated prior to PCI, additional heparin boluses may be required. Do not administer heparin after PCI. Discontinue eptifibatide in persons who require thrombolytic therapy. Discontinue eptifibatide at least 2 to 4 hours prior to CABG surgery. Guidelines recommend a GP IIb/IIIa inhibitor at the time of PCI for persons with UA and NSTEMI with intermediate/high-risk features (e.g., positive troponin) treated with early invasive strategy and dual antiplatelet therapy. This regimen is also recommended at the time of PCI for UA/NSTEMI with high-risk features (e.g., elevated troponin) who are receiving heparin, not treated with bivalirudin, not adequately pretreated with ticagrelor, and regardless of clopidogrel pretreatment.
For the treatment acute myocardial infarction, STEMI managed with percutaneous coronary intervention (PCI):
Intravenous dosage:
Adults: 180 mcg/kg (Max: 22.6 mg) IV bolus, followed by 2 mcg/kg/minute (Max: 15 mg/hour) continuous IV infusion until hospital discharge or 18 to 24 hours after PCI, whichever is earlier. Administer an additional 180 mcg/kg IV bolus 10 minutes after the first bolus. A minimum of 12 hours of infusion is recommended. Administer concomitantly with aspirin and heparin. Dose heparin to maintain a target ACT of 200 to 300 seconds. Administer heparin 60 units/kg IV bolus initially in patients not treated with heparin within 6 hours prior to PCI; additional boluses may be administered during PCI to maintain target ACT. Do not administer heparin after PCI. Discontinue eptifibatide in patients who require thrombolytic therapy. Discontinue eptifibatide at least 2 to 4 hours prior to CABG surgery. Guidelines recommend the adjunctive use of GP IIb/IIIa inhibitors at the time of primary PCI in select patients with STEMI (i.e., large thrombus burden or inadequate P2Y12 receptor antagonist loading) who are receiving heparin and treated with or without clopidogrel or stenting.
Maximum Dosage Limits:
-Adults
180 mcg/kg (Max: 22.6 mg) IV bolus and 2 mcg/kg/minute (Max: 15 mg/hour) continuous IV infusion.
-Geriatric
180 mcg/kg (Max: 22.6 mg) IV bolus and 2 mcg/kg/minute (Max: 15 mg/hour) continuous IV infusion.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
CrCl less than 50 mL/minute: Reduce the continuous infusion to 1 mcg/kg/minute (Max: 7.5 mg/hour) IV.
Intermittent hemodialysis
Eptifibatide is contraindicated in patients dependent on renal dialysis.
*non-FDA-approved indication
Abrocitinib: (Contraindicated) Concurrent use with platelet glycoprotein IIb/IIIa inhibitors is contraindicated during the first 3 months of abrocitinib therapy due to an increased risk of bleeding with thrombocytopenia.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Acetaminophen; Aspirin: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Acetaminophen; Ibuprofen: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Ado-Trastuzumab emtansine: (Moderate) Use caution if coadministration of platelet inhibitors with ado-trastuzumab emtansine is necessary due to reports of severe and sometimes fatal hemorrhage, including intracranial bleeding, with ado-trastuzumab emtansine therapy. Consider additional monitoring when concomitant use is medically necessary. While some patients who experienced bleeding during ado-trastuzumab therapy were also receiving anticoagulation therapy, others had no known additional risk factors.
ADP receptor antagonists: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding.
Alteplase: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Aminolevulinic Acid: (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Amlodipine; Celecoxib: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Anagrelide: (Moderate) Although anagrelide inhibits platelet aggregation at high doses, there is a potential additive risk for bleeding if anagrelide is given in combination with other agents that effect hemostasis such as platelet glycoprotein IIb/IIIa inhibitors including abciximab, eptifibatide, and tirofiban.
Antithrombin III: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Antithymocyte Globulin: (Moderate) An increased risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia, such as antithymocyte globulin. Platelet inhibitors should be used cautiously in patients with thrombocytopenia following the administration of antithymocyte globulin or other drugs that cause significant thrombocytopenia due to the increased risk of bleeding.
Apixaban: (Major) The concomitant use of apixaban and platelet inhibitors (e.g, aspirin) may increase the risk of bleeding. In the ARISTOTLE trial (comparative trial of apixaban and warfarin in patients with nonvalvular atrial fibrillation), concomitant use of aspirin increased the bleeding risk of apixaban from 1.8%/year to 3.4%/year. If given concomitantly, patients should be educated about the signs and symptoms of bleeding and be instructed to report them immediately or go to an emergency room.
Argatroban: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g., clopidogrel, platelet glycoprotein IIb/IIIa inhibitors, ticlopidine, etc.) in combination with argatroban.
Arsenic Trioxide: (Moderate) Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur when eptifibatide is used concomitantly with agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Aspirin, ASA: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Caffeine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Dipyridamole: (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis such as platelet glycoprotein IIb/IIIa inhibitors including abciximab, eptifibatide, and tirofiban. (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Omeprazole: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Oxycodone: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Betrixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and platelet inhibitors are used concomitantly. Coadministration of betrixaban and platelet inhibitors may increase the risk of bleeding.
Bexarotene: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including bexarotene.
Bivalirudin: (Moderate) When used as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI), bivalirudin is intended for use with aspirin (300 to 325 mg/day PO) and has been studied only in patients receiving concomitant aspirin. Generally, an additive risk of bleeding may be seen in patients receiving other platelet inhibitors (other than aspirin). In clinical trials in patients undergoing PTCA, patients receiving bivalirudin with heparin, warfarin, or thrombolytics had increased risks of major bleeding events compared to those receiving bivalirudin alone. According to the manufacturer, the safety and effectiveness of bivalirudin have not been established when used in conjunction with platelet inhibitors other than aspirin. However, bivalirudin has been safely used as an alternative to heparin in combination with provisional use of platelet glycoprotein IIb/IIIa inhibitors during angioplasty (REPLACE-2). In addition, two major clinical trials have evaluated the use of bivalirudin in patients receiving streptokinase following acute myocardial infarction (HERO-1, HERO-2). Based on the these trials, bivalirudin may be considered an alternative to heparin therapy for use in combination with streptokinase for ST-elevation MI. Bivalirudin has not been sufficiently studied in combination with other more specific thrombolytics.
Bupivacaine; Meloxicam: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Caplacizumab: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Celecoxib: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Celecoxib; Tramadol: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Chlorambucil: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as chlorambucil.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Cilostazol: (Moderate) Because cilostazol is a platelet aggregation inhibitor, a potential additive risk for bleeding exists if cilostazol is given with other agent that affect hemostasis such as platelet glycoprotein IIb/IIIa inhibitors including abciximab, eptifibatide, and tirofiban.
Citalopram: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
Cladribine: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Clofarabine: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Clopidogrel: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding.
Collagenase: (Moderate) Cautious use of injectable collagenase by patients taking platelet inhibitors is advised. The efficacy and safety of administering injectable collagenase to a patient taking a platelet inhibitor within 7 days before the injection are unknown. Receipt of injectable collagenase may cause an ecchymosis or bleeding at the injection site.
Dabigatran: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Dalteparin: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Danazol: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Dasatinib: (Moderate) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Defibrotide: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Deoxycholic Acid: (Moderate) Use deoxycholic acid with caution in patients receiving platelet inhibitors. Excessive bruising or bleeding may occur in and around the treatment area.
Desvenlafaxine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with a platelet inhibitor and to promptly report any bleeding events to the practitioner.
Diclofenac: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Diclofenac; Misoprostol: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Diflunisal: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Diphenhydramine; Naproxen: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Dipyridamole: (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis such as platelet glycoprotein IIb/IIIa inhibitors including abciximab, eptifibatide, and tirofiban.
Duloxetine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with a platelet inhibitor and to promptly report any bleeding events to the practitioner.
Edoxaban: (Major) Coadministration of edoxaban and platelet inhibitors should be avoided due to an increased risk of bleeding during concurrent use. Occasionally, short-term coadministration may be necessary in patients transitioning to and from edoxaban. Long-term coadminstration is not recommended. Promptly evaluate any signs or symptoms of blood loss in patients on concomitant therapy.
Enoxaparin: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Escitalopram: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
Etodolac: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Fenoprofen: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Fludarabine: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Fluoxetine: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
Flurbiprofen: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Fluvoxamine: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
Fondaparinux: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Garlic, Allium sativum: (Moderate) Use together with caution. Garlic produces clinically significant antiplatelet effects, and a risk for bleeding may occur if platelet inhibitors are given in combination with garlic.
Ginger, Zingiber officinale: (Moderate) Ginger inhibits thromboxane synthetase, a platelet aggregation inducer, and is a prostacyclin agonist so additive bleeding may occur if platelet inhibitors are given in combination with ginger, zingiber officinale.
Ginkgo, Ginkgo biloba: (Moderate) Monitor for signs or symptoms of bleeding with coadministration of ginkgo biloba and platelet inhibitors as an increased bleeding risk may occur. Although data are mixed, ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with ginkgo biloba, with or without concomitant drug therapy.
Green Tea: (Moderate) Green tea has demonstrated antiplatelet and fibrinolytic actions in animals. It is possible that the use of green tea may increase the risk of bleeding if co administered with aspirin. Caution and careful monitoring of clinical and/or laboratory parameters are warranted with this combination.
Heparin: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding. In addition, large doses of salicylates (>= 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. In clinical trials with eptifibatide, aspirin and heparin were administered concomitantly. Eptifibatide has been administered with a thrombolytic agent in a small number of patients. In the IMPACT II study, 15 patients received a thrombolytic agent with the 135/0.5 dosing regimen, 2 of whom experienced a major bleed. In the PURSUIT study, 40 patients who received eptifibatide (180 mcg/kg bolus, then 2 mcg/kg/min) also received a thrombolytic agent, 10 of whom experienced a major bleed. In another acute MI study (n=181), eptifibatide (180 mcg/kg bolus, then up to 2 mcg/kg/min for up to 72 hours) was administered concomitantly with streptokinase (1.5 mU over 60 min). At the highest studied infusion rates (1.3 to 2 mcg/kg/min), eptifibatide was associated with an increase in the incidence of bleeding and transfusions compared to the incidence seen with streptokinase alone.
Hydrocodone; Ibuprofen: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with platelet function such as platelet inhibitors; the risk of bleeding may be increased. If coadministration with platelet inhibitors is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia.
Ibrutinib: (Moderate) The concomitant use of ibrutinib and antiplatelet agents such as eptifibatide may increase the risk of bleeding; monitor patients for signs of bleeding. Severe bleeding events have occurred with ibrutinib therapy including intracranial hemorrhage, GI bleeding, hematuria, and post procedural hemorrhage; some events were fatal. The mechanism for bleeding with ibrutinib therapy is not well understood.
Ibuprofen: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Ibuprofen; Famotidine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Ibuprofen; Oxycodone: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Icosapent ethyl: (Moderate) Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). Because omega-3 fatty acids inhibit platelet aggregation, caution is advised when icosapent ethyl is used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 36 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant icosapent ethyl therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Iloprost: (Moderate) When used concurrently with platelet inhibitors, inhaled iloprost may increase the risk of bleeding.
Indomethacin: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and platelet glycoprotein IIb/IIIa inhibitors due to the potential risk of bleeding from thrombocytopenia. Consider discontinuation of platelet glycoprotein IIb/IIIa inhibitors in a patient taking inotersen with a platelet count of less than 50,000 per microliter.
Intravenous Lipid Emulsions: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Ketoprofen: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Ketorolac: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Levomilnacipran: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of levomilnacipran and platelet inhibitors. Serotonin-norepinephrine reuptake inhibitors (SNRIs) affect platelet activation; therefore, concomitant use may increase the risk of bleeding.
Lomustine, CCNU: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as lomustine.
Meclofenamate Sodium: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Mefenamic Acid: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Meloxicam: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Mercaptopurine, 6-MP: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Methoxsalen: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
Methylsulfonylmethane, MSM: (Moderate) Increased effects from concomitant anticoagulant drugs including increased bruising or blood in the stool have been reported in patients taking methylsulfonylmethane, MSM. Although these effects have not been confirmed in published medical literature or during clinical studies, clinicians should consider using methylsulfonylmethane, MSM with caution in patients who are taking anticoagulants or antiplatelets including clopidogrel until data confirming the safety of these drug combinations are available. During one of the available, published clinical trials in patients with osteoarthritis, those patients with bleeding disorders or using anticoagulants or antiplatelets were excluded from enrollment. Patients who choose to consume methylsulfonylmethane, MSM while receiving clopidogrel should be observed for increased bleeding.
Milnacipran: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of milnacipran and platelet inhibitors. Serotonin-norepinephrine reuptake inhibitors (SNRIs) affect platelet activation; therefore, concomitant use may increase the risk of bleeding.
Mycophenolate: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Nabumetone: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Naproxen: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Naproxen; Esomeprazole: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Naproxen; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Nelarabine: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Obinutuzumab: (Moderate) Fatal hemorrhagic events have been reported in patients treated with obinutuzumab; all events occured during cycle 1. Monitor all patients for thrombocytopenia and bleeding, and consider withholding concomitant medications which may increase bleeding risk (i.e., anticoagulants, platelet inhibitors), especially during the first cycle.
Olanzapine; Fluoxetine: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
Oxaprozin: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Paroxetine: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
Pentosan: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Pentostatin: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Pentoxifylline: (Moderate) A potential additive risk for bleeding exists if platelet inhibitors are given in combination with other agents that affect hemostasis such as pentoxifylline.
Photosensitizing agents (topical): (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Piroxicam: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Prasterone is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Prasterone is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
Prasugrel: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding.
Purine analogs: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Reteplase, r-PA: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Rivaroxaban: (Major) Avoid concurrent administration of platelet inhibitors such as eptifibatide with rivaroxaban unless the benefit outweighs the risk of increased bleeding. An increase in bleeding time to 45 minutes was observed in 2 drug interaction studies where another platelet inhibitor and rivaroxaban (15 mg single dose) were coadministered in healthy subjects. In the first study, the increase in bleeding time to 45 minutes was observed in approximately 45% of patients. Approximately 30% of patients in the second study had the event. The change in bleeding time was approximately twice the maximum increase seen with either drug alone. No change in the pharmacokinetic parameters of either drug were noted.
Selective serotonin reuptake inhibitors: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
Selumetinib: (Moderate) Closely monitor for bleeding if coadministration of selumetinib and platelet inhibitors is necessary as concurrent use may increase the bleeding risk; adjust the platelet inhibitor dose as appropriate. Selumetinib contains vitamin E which can inhibit platelet aggregation.
Sertraline: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
Sulindac: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Sumatriptan; Naproxen: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Tenecteplase: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Thioguanine, 6-TG: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Thrombolytic Agents: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Ticagrelor: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding.
Tipranavir: (Moderate) Caution should be used when administering tipranavir to patients receiving platelet inhibitors. In clinical trials, there have been reports of intracranial bleeding, including fatalities, in HIV infected patients receiving tipranavir as part of combination antiretroviral therapy. In many of these reports, the patients had other medical conditions (CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcoholism/alcohol abuse) or were receiving concomitant medications, including platelet inhibitors, that may have caused or contributed to these events.
Tolmetin: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Trazodone: (Moderate) Platelet aggregation may be impaired by trazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking trazodone concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Treprostinil: (Moderate) Monitor patients for signs and symptoms of bleeding if treprostinil is administered with eptifibatide. Treprostinil inhibits platelet aggregation; eptifibatide is a platelet inhibitor. Coadministration increases the risk of bleeding.
Venlafaxine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with a platelet inhibitor and to promptly report any bleeding events to the practitioner.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with platelet inhibitors is necessary due to the risk of decreased verteporfin efficacy. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease platelet aggregation could decrease the efficacy of verteporfin therapy.
Vilazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking vilazodone concurrently with salicylates or other platelet inhibitors and to promptly report any bleeding events to the practitioner. Platelet aggregation may be impaired by vilazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., aspirin, cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors).
Vorapaxar: (Moderate) Because vorapaxar inhibits platelet aggregation, a potential additive risk for bleeding exists if vorapaxar is given in combination with other agents that affect hemostasis such as platelet glycoprotein IIb/IIIa inhibitors including abciximab, eptifibatide, and tirofiban.
Vorinostat: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of eptifibatide and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors.
Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Warfarin: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Eptifibatide is a competitive inhibitor of glycoprotein (GP) IIb/IIIa preventing the binding of fibrinogen, von Willebrand factor (vWF), and other adhesive ligands to the GP IIb/IIIa receptor on activated platelets. "Integrins", which are found on virtually all cell types, are a family of adhesion molecules that mediate many physiologic responses. Unlike many of the other integrins, GP IIb/IIIa is platelet specific and is also the most abundant receptor found on activated platelets, with about 50,000 copies/cell. Fibrinogen is the principal ligand to bind to the GP IIb/IIIa receptor. The binding of fibrinogen and, to a lesser extent other ligands such as vWF, to the GP IIb/IIIa receptor results in cross-linking between platelets and is the final common pathway of platelet aggregation, which ultimately leads to thrombus formation. Unlike abciximab and tirofiban, which bind to GP IIb/IIIa via an arginine-glycine-aspartic acid (RGD) sequence, eptifibatide contains the lysine-glycine-aspartic acid (KGD) peptide sequence that is thought to create greater specificity for the GP IIb/IIIa receptor. Unlike abciximab, eptifibatide does not bind to the vitronectin receptor. The clinical relevance of binding to vitronectin is not fully understood. Glycoprotein IIb/IIIa inhibitors can prevent platelet aggregation regardless of the agonist involved; thus, eptifibatide will block thrombin-induced platelet aggregation while aspirin will not. When administered alone, eptifibatide has no effect on PT or aPTT.
Eptifibatide is administered intravenously. The pharmacokinetics of eptifibatide are linear and dose-proportional for bolus doses of 90 to 250 mcg/kg and infusion rates of 0.5 to 3 mcg/kg/minute. About 25% of eptifibatide is bound to plasma protein. No major metabolites of eptifibatide have been detected in human plasma. In healthy subjects, renal clearance accounts for about 50% of total body clearance, with the majority of drug excreted in the urine as eptifibatide, deaminated eptifibatide, and other, more polar metabolites. Clearance in patients with coronary artery disease is 55 mL/kg/hour. The elimination half-life of eptifibatide is about 2.5 hours.
Eptifibatide inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner. Inhibition of platelet aggregation is 84% at 15 minutes after an eptifibatide 180 mcg/kg IV bolus (followed by a 2 mcg/kg/minute continuous IV infusion). Inhibition of platelet aggregation is more than 90% at steady-state and less than 50% at hours after infusion discontinuation. At 6 hours after discontinuation, bleeding time prolongation is 1.4 times baseline.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Special Populations
Hepatic Impairment
No pharmacokinetic studies have been conducted in patients with hepatic impairment.
Renal Impairment
Eptifibatide clearance is reduced approximately 50% and steady-state plasma concentrations are doubled in patients with moderate to severe renal impairment (CrCl less than 50 mL/minute).
Geriatric
Elderly patients with coronary artery disease demonstrate lower total body clearance and higher plasma concentrations when given the same eptifibatide dose as younger patients.