Aggrastat

GP IIb/IIIa (glycoprotein) Antagonist Platelet Aggregation Inhibitors

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Preparation
Tirofiban is available only as a premixed solution.
To open the premixed bag, tear off the foil overpouch. The plastic may appear opaque due to moisture absorption during sterilization; this should gradually diminish. Check for leaks by gently squeezing the inner bag. Discard the solution if leaks are found or if sterility cannot be confirmed. Do not use unless the solution is clear and the seal is intact.
To prepare the bolus dose, withdraw the appropriate volume from the premixed vial or bag into a syringe. Do not dilute.
 
IV Infusion
Administer the bolus dose within 5 minutes via a syringe or IV pump. For patients weighing 167 kg or more, administer the bolus via syringe from the 15 mL premixed bolus vial, to ensure that delivery time does not exceed 5 minutes.
Administer the maintenance infusion via an IV pump immediately after bolus dose administration.
Do NOT administer tirofiban through the same line as diazepam. Do not add other drugs or remove solution directly from the bag with a syringe.
Tirofiban may be administered in the same IV line as heparin, atropine, dobutamine, dopamine, epinephrine, famotidine, furosemide, lidocaine, midazolam, morphine, nitroglycerin, potassium chloride, and propranolol.

bradycardia / Rapid / 4.0-4.0
GI bleeding / Delayed / 0-1.0
intracranial bleeding / Delayed / 0-1.0
retroperitoneal bleeding / Delayed / 0-1.0
hematemesis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

edema / Delayed / 2.0-2.0
hypotension / Rapid / 2.0-2.0
hematoma / Early / Incidence not known
bleeding / Early / Incidence not known
hemoptysis / Delayed / Incidence not known
platelet dysfunction / Delayed / Incidence not known
hematuria / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known

pelvic pain / Delayed / 6.0-6.0
dizziness / Early / 3.0-3.0
hyperhidrosis / Delayed / 2.0-2.0
nausea / Early / 2.0-2.0
headache / Early / 2.0-2.0
fever / Early / 2.0-2.0
vomiting / Early / 2.0-2.0
chills / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
rash / Early / Incidence not known

Aggrastat

Rx

Intravenous nonpeptide, platelet glycoprotein IIb/IIIa inhibitor
For rate reduction of thrombotic cardiovascular events in patients with non-ST elevation acute coronary syndromes
Reversible platelet inhibition within 4—8 hours of discontinuation

25 mcg/kg IV bolus, followed by 0.15 mcg/kg/minute for up to 18 hours. Guidelines support GP IIb/IIIa inhibitors at the time of percutaneous coronary intervention (PCI) for persons with unstable angina (UA) and NSTEMI with intermediate/high-risk features (e.g., positive troponin) treated with early invasive strategy and dual antiplatelet therapy; a GP IIb/IIIa inhibitor may be considered as part of initial antiplatelet therapy, and tirofiban is a preferred option. This regimen is also recommended at the time of PCI for UA/NSTEMI with high-risk features (e.g., elevated troponin) who are receiving unfractionated heparin (UFH), not treated with bivalirudin, not adequately pretreated with ticagrelor, and regardless of clopidogrel pretreatment. For persons referred for coronary artery bypass graft surgery (CABG), discontinue tirofiban at least 2 to 4 hours prior to surgery.

25 mcg/kg IV bolus, followed by 0.15 mcg/kg/minute for up to 18 to 24 hours. Guidelines support the adjunctive use of GP IIb/IIIa inhibitors at the time of primary percutaneous coronary intervention (PCI) in select patients with STEMI (i.e., large thrombus burden or inadequate P2Y12 receptor antagonist loading) who are receiving unfractionated heparin (UFH) and treated with or without clopidogrel or stenting. Discontinue tirofiban at least 2 to 4 hours prior to urgent coronary artery bypass graft surgery (CABG).

25 mcg/kg IV within 5 minutes followed by 0.15 mcg/kg/minute for 18 to 48 hours. Clinical practice guidelines support the adjunctive use of GP IIb/IIIa inhibitors at the time of elective percutaneous coronary intervention (PCI) in patients with stable ischemic heart disease who are receiving unfractionated heparin (UFH) and treated with or without clopidogrel or stenting.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

CrCl 60 mL/minute or less: 25 mcg/kg IV within 5 minutes followed by 0.075 mcg/kg/minute.
 
Intermittent hemodialysis
Dosage recommendations in patients undergoing intermittent hemodialysis have not been established. Tirofiban is removed by hemodialysis; however, plasma clearance of tirofiban is significantly decreased (more than 50%) in patients with a CrCl less than 30 mL/minute, including patients requiring hemodialysis.

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 tirofiban. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Acetaminophen; Aspirin: (Moderate) Unless contraindicated, aspirin is used in combination with tirofiban. 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 tirofiban. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
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.
Altretamine: (Moderate) An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as altretamine.
Aminolevulinic Acid: (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Patients who receive omeprazole concomitantly with tirofiban may have a higher rate of tirofiban clearance than patients who do not receive omeprazole. The clinical significance of this is unknown.
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 tirofiban and other agents that effect 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.
Aspirin, ASA: (Moderate) Unless contraindicated, aspirin is used in combination with tirofiban. 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 tirofiban. 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 tirofiban. 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 tirofiban. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Carisoprodol: (Moderate) Unless contraindicated, aspirin is used in combination with tirofiban. 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 tirofiban. 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 tirofiban. 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 tirofiban. 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 tirofiban. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy. (Minor) Patients who receive omeprazole concomitantly with tirofiban may have a higher rate of tirofiban clearance than patients who do not receive omeprazole. The clinical significance of this is unknown.
Aspirin, ASA; Oxycodone: (Moderate) Unless contraindicated, aspirin is used in combination with tirofiban. 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.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Unless contraindicated, aspirin is used in combination with tirofiban. 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.
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.
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.
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.
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 tirofiban and other agents that affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Dalteparin: (Moderate) Concomitant use of tirofiban and other agents that effect 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.
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.
Desirudin: (Moderate) Concomitant use of tirofiban and other agents that effect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
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.
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: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including tirofiban, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
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.
Fondaparinux: (Moderate) Concomitant use of tirofiban and other agents that effect 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 tirofiban and other agents that effect hemostasis, such as anticoagulants, other platelet inhibitors, NSAIDs, and thrombolytic agents, 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 tirofiban, many patients received aspirin and heparin concomitantly. In these studies, the combination of tirofiban with heparin and aspirin has been associated with an increase in bleeding compared to heparin and aspirin alone. While administering tirofiban and heparin, the aPTT should be checked 6 hours after the start of the heparin infusion; heparin should be adjusted to maintain the aPTT approximately 2-times control. No information is available about the concomitant use of tirofiban with thrombolytic agents.
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 tirofiban 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.
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.
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.
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.
Levothyroxine: (Minor) Data from the PRISM study, indicate that patients who received levothyroxine or omeprazole concomitantly with tirofiban had a higher rate of tirofiban clearance than patients who did not receive levothyroxine or omeprazole. The clinical significance of this is unknown.
Levothyroxine; Liothyronine (Porcine): (Minor) Data from the PRISM study, indicate that patients who received levothyroxine or omeprazole concomitantly with tirofiban had a higher rate of tirofiban clearance than patients who did not receive levothyroxine or omeprazole. The clinical significance of this is unknown.
Levothyroxine; Liothyronine (Synthetic): (Minor) Data from the PRISM study, indicate that patients who received levothyroxine or omeprazole concomitantly with tirofiban had a higher rate of tirofiban clearance than patients who did not receive levothyroxine or omeprazole. The clinical significance of this is unknown.
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.
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.
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.
Omeprazole: (Minor) Patients who receive omeprazole concomitantly with tirofiban may have a higher rate of tirofiban clearance than patients who do not receive omeprazole. The clinical significance of this is unknown.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Patients who receive omeprazole concomitantly with tirofiban may have a higher rate of tirofiban clearance than patients who do not receive omeprazole. The clinical significance of this is unknown.
Omeprazole; Sodium Bicarbonate: (Minor) Patients who receive omeprazole concomitantly with tirofiban may have a higher rate of tirofiban clearance than patients who do not receive omeprazole. The clinical significance of this is unknown.
Pentosan: (Moderate) Concomitant use of tirofiban and other agents that effect 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.
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.
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.
Rivaroxaban: (Major) Avoid concurrent administration of platelet inhibitors such as clopidogrel with rivaroxaban unless the benefit outweighs the risk of increased bleeding. An increase in bleeding time to 45 minutes was observed in two drug interaction studies where clopidogrel (300 mg loading dose followed by 75 mg daily maintenance dose) 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.
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.
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.
Treprostinil: (Moderate) Monitor patients for signs and symptoms of bleeding if treprostinil is administered with tirofiban. Treprostinil inhibits platelet aggregation; tirofiban 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.
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 tirofiban and other agents that effect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.

Aggrastat/Tirofiban/Tirofiban Hydrochloride Intravenous Inj Sol: 1mL, 50mcg

25 mcg/kg IV bolus followed by 0.15 mcg/kg/minute for up to 18 hours.

25 mcg/kg IV bolus followed by 0.15 mcg/kg/minute for up to 18 hours.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Tirofiban 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. Tirofiban binds to GP IIb/IIIa via an arginine-glycine-aspartic acid (RGD) sequence. Unlike abciximab, tirofiban 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, tirofiban will block thrombin-induced platelet aggregation while aspirin will not. When administered alone, tirofiban has no effect on PT or aPTT.

Tirofiban is administered intravenously. Tirofiban is not highly bound to plasma proteins and protein binding is concentration independent over the range of 0.01 to 25 mcg/mL. In human plasma, the unbound fraction is about 35%. Metabolism of tirofiban appears to be limited. Renal clearance accounts for about 39% of plasma clearance. About 65% of a dose of tirofiban is excreted in urine and about 25% in feces, both largely as unchanged drug. The elimination half-life of tirofiban is approximately 2 hours (range: 1.7 to 2 hours).
 
Tirofiban inhibits platelet function, as demonstrated by its ability to inhibit ex vivo adenosine phosphate (ADP)-induced platelet aggregation and prolong bleeding time. Platelet aggregation is inhibited by > 90% approximately 10 minutes after administering the bolus dose and initiating the maintenance infusion. The addition of heparin does not affect the percentage of patients with > 70% inhibition of platelet aggregation but does increase the average bleeding time as well as the number of patients with bleeding times prolonged to > 30 minutes. Platelet inhibition is reversible following cessation of the infusion. Platelet aggregation returns to near baseline in about 90% of patients within 4 to 8 hours.

Although not definitive, case reports have not established an association with tirofiban use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. Untreated myocardial infarction can be fatal to the pregnant woman and fetus. Animal studies with tirofiban at intravenous doses up to 5 and 13 times the maximum recommended daily human dose for rat and rabbit, respectively, when compared on a body surface area basis have revealed no evidence of harm to the fetus.

There are no data on the presence of tirofiban in human milk, the effects of the drug on the breast-fed infant, or the effects of the drug on human milk production. However, tirofiban is present in rat milk. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for tirofiban and any potential adverse effects on the breast-fed infant from tirofiban or the underlying maternal condition.