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Anti-platelet Agents

Anti-platelet Agents

abciximab (Reopro ®): Aggrenox ® (dipyridamole/ASA):
anagrelide (Agrylin ®): cangrelor injection -KENGREAL™
cilostazol (Pletal ®) --
clopidogrel (Plavix ® ): dipyridamole (Persantine ®):
eptifabatide (Integrilin ®): prasugrel - EFFIENT™:
ticagrelor -BRILINTA™: ticlopidine (Ticlid ®):
tirofiban (Aggrastat ®): vorapaxar -ZONTIVITY™ -->

Thrombopoietin receptor agonists

eltrombopag olamine - PROMACTA® --
Please see package insert for additional information and possible updates. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.    [  Read the disclaimer    |   <<Back     ]

abciximab (Reopro ®):  top of page

Platelet aggregation inhibition: (PCI): 0.25 mg/kg IV 10–60 minute prior to PCI, then 0.125 mcg/kg/minute (Maximum 10 mcg/min) IV Infusion x 12 hours.

The safety and efficacy of Abciximab have only been investigated with concomitant administration of heparin and aspirin as described in CLINICAL STUDIES.  In patients with failed PCls, the continuous infusion of Abciximab should be stopped because there is no evidence for Abciximab efficacy in that setting.  In the event of serious bleeding that cannot be controlled by compression, Abciximab and heparin should be discontinued immediately.

Filter the bolus injection using a sterile, non-pyrogenic, low protein-binding 0.2 or 0.22 m m filter (Millipore SLGV025LS or equivalent).

Aggrenox ® (dipyridamole/ASA): top of page

 INDICATIONS:  AGGRENOX (aspirin/extended-release dipyridamole) is indicated to reduce the risk of stroke in patients who have had transient ischemia of the brain or completed ischemic stroke due to thrombosis.

DOSAGE AND ADMINISTRATION:  The recommended dose of AGGRENOX (aspirin/extended-release dipyridamole) is one capsule given orally twice daily, one in the morning and one in the evening. The capsules should be swallowed whole without chewing. AGGRENOX capsules may be administered with or without food.

AGGRENOX is not interchangeable with the individual components of aspirin and Persantine® Tablets.

Supplied:  Each hard gelatin capsule contains 200 mg dipyridamole in an extended-release form and 25 mg aspirin, as an immediate-release sugar-coated tablet.   [200 mg /25 mg]

anagrelide (Agrylin ®): top of page

 INDICATIONS:   AGRYLIN Capsules are indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events.

DOSAGE AND ADMINISTRATION:  Treatment with AGRYLIN Capsules should be initiated under close medical supervision. The recommended starting dosage of AGRYLIN is 0. 5 mg orally four times daily or 1 mg orally twice daily which should be maintained for at least one week. Dosage should then be adjusted to the lowest effective dosage required to reduce and maintain platelet count below 600,000/L, and ideally to the normal range. The dosage should be increased by not more than 0.5 mg/day in any one week. Dosage should not exceed 10 mg/day or 2.5 mg in a single dose.

Supplied: [ 0.5 mg , 1 mg  capsule]

cilostazol (Pletal ®)  top of page

Mechanism of Action:
The mechanism of the effects of cilostazol tablets on the symptoms of intermittent claudication is not fully understood. Cilostazol tablets and several of its metabolites are cyclic AMP (cAMP) phosphodiesterase III inhibitors (PDE III inhibitors), inhibiting phosphodiesterase activity and suppressing cAMP degradation with a resultant increase in cAMP in platelets and blood vessels, leading to inhibition of platelet aggregation and vasodilation, respectively.

Cilostazol tablets reversibly inhibits platelet aggregation induced by a variety of stimuli, including thrombin, ADP, collagen, arachidonic acid, epinephrine, and shear stress. Effects on circulating plasma lipids have been examined in patients taking cilostazol tablets.

INDICATIONS AND USAGE
Cilostazol is indicated for the reduction of symptoms of intermittent claudication, as indicated by an increased walking distance.

CONTRAINDICATIONS
Cilostazol and several of its metabolites are inhibitors of phosphodiesterase III. Several drugs with this pharmacologic effect have caused decreased survival compared to placebo in patients with class III-IV congestive heart failure. Cilostazol is contraindicated in patients with congestive heart failure of any severity.

Cilostazol is contraindicated in patients with haemostatic disorders or active pathologic bleeding, such as bleeding peptic ulcer and intracranial bleeding. Cilostazol inhibits platelet aggregation in a reversible manner.

Cilostazol is contraindicated in patients with known or suspected hypersensitivity to any of its components.

Dosing (Adults): Peripheral vascular disease: 100 mg orally twice daily taken at least 30 minutes before or 2 hours after breakfast and dinner. Dosage should be reduced to 50 mg twice daily during concurrent therapy with inhibitors of CYP3A4 or CYP2C19.

Supplied: 50 mg, 100 mg tablet.

clopidogrel (Plavix ® ):  top of page

INDICATIONS:  Plavix (clopidogrel bisulfate) is indicated for the reduction of atherothrombotic events as follows:

* Recent MI, Recent Stroke or Established Peripheral Arterial Disease:  For patients with a history of recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease, Plavix has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death.
* Acute Coronary Syndrome:   For patients with non-ST-segment elevation acute coronary syndrome (unstable angina/non-Q-wave MI) including patients who are to be managed medically and those who are to be managed with percutaneous coronary intervention (with or without stent) or CABG, Plavix has been shown to decrease the rate of a combined endpoint of cardiovascular death, MI, or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, stroke, or refractory ischemia.
For patients with ST-segment elevation acute myocardial infarction, Plavix has been shown to reduce the rate of death from any cause and the rate of a combined endpoint of death, re-infarction or stroke. This benefit is not known to pertain to patients who receive primary angioplasty.

DOSAGE AND ADMINISTRATION:
Recent MI, Recent Stroke, or Established Peripheral Arterial Disease
The recommended daily dose of Plavix is 75 mg once daily.

Acute Coronary Syndrome
For patients with non-ST-segment elevation acute coronary syndrome (unstable angina/non-Q-wave MI), Plavix should be initiated with a single 300-mg loading dose and then continued at 75 mg once daily. Aspirin (75 mg-325 mg once daily) should be initiated and continued in combination with Plavix. In CURE, most patients with Acute Coronary Syndrome also received heparin acutely.

For patients with ST-segment elevation acute myocardial infarction, the recommended dose of Plavix is 75 mg once daily, administered in combination with aspirin, with or without thrombolytics. Plavix may be initiated with or without a loading dose (300 mg was used in CLARITY --  Review CLINICAL STUDIES).

Plavix can be administered with or without food.
No dosage adjustment is necessary for elderly patients or patients with renal disease.

Supplied:  75 mg,  300 mg tablet.

dipyridamole (Persantine ®):  top of page

INDICATIONS:  Dipyridamole is indicated as an adjunct to coumarin anticoagulants in the prevention of postoperative thromboembolic complications of cardiac valve replacement.
DOSAGE AND ADMINISTRATION:
Adjunctive Use in Prophylaxis of Thromboembolism after Cardiac Valve Replacement

The recommended dose is 75-100 mg four times daily as an adjunct to the usual warfarin therapy. Please note that aspirin is not to be administered concomitantly with coumarin anticoagulants.

Supplied:  25 mg, 50 mg and 75 mg tablets.

eptifabatide (Integrilin ®):  top of page

ADMINISTRATION:

Administration
: Bolus: withdraw dose from 10ml vial and give by IV push over 1-2 minutes. Continuous infusion: administer calculated rate directly from 100ml vial.

Properties: Onset: within 1 hr. T1/2 = 2.5 hours. Platelet fcn restored in @ 4hours after discontinuation. [Supplied: 0.75 mg/ml (100ml) vial. 20 mg/10 ml vial.]

DOSAGE
Acute Coronary Syndrome: The recommended adult dosage of eptifibatide in patients with acute coronary syndrome and normal renal function is an intravenous bolus of 180 µg/kg (maximum: 22.6 mg) over 1-2 minutes as soon as possible following diagnosis, followed by a continuous infusion of 2.0 µg/kg/min (maximum: 15 mg/hour) until hospital discharge or initiation of CABG surgery, up to 72 hours. If a patient is to undergo a percutaneous coronary intervention (PCI) while receiving eptifibatide, the infusion should be continued up to hospital discharge, or for up to 18-24 hours after the procedure, whichever comes first, allowing for up to 96 hours of therapy. Concurrent aspirin (160-325 mg initially and daily thereafter) and heparin therapy (target aPTT 50-70 seconds) are recommended.

Dosing adjustment in renal impairment: Patients with CRCL less than 50 ml/min: The recommended adult dosage of eptifibatide in patients with acute coronary syndrome with an estimated CRCL <50 ml/min (using the Cockcroft-Gault equation) is an IV bolus of 180 µg/kg (maximum: 22.6 mg) as soon as possible following diagnosis, immediately followed by a continuous infusion of 1.0 µg/kg/min (maximum: 7.5 mg/hour).

Percutaneous Coronary Intervention (PCI): The recommended adult dosage of eptifibatide in patients with normal renal function is an intravenous bolus of 180 µg/kg (maximum: 22.6 mg) over 1-2 minutes administered immediately before the initiation of PCI followed by a continuous infusion of 2.0 µg/kg/min (maximum: 15 mg/hour) and a second 180 µg/kg bolus (maximum: 22.6 mg) 10 minutes after the first bolus. Infusion should be continued until hospital discharge, or for up to 18 to 24 hours, whichever comes first. A minimum of 12 hours of infusion is recommended. Concurrent aspirin (160-325 mg 1-24 hours before PCI and daily thereafter) and heparin therapy (ACT 200-300 seconds during PCI) are recommended. Heparin infusion after PCI is discouraged.
Dosing adjustment in renal impairment: Patients with CRCL less than 50 mL/min: The recommended adult dose of eptifibatide in patients with an estimated CRCL < 50 ml/min (using the Cockcroft-Gault equation) is an IV bolus of 180 µg/kg (maximum: 22.6 mg) administered immediately before the initiation of the procedure, immediately followed by a continuous infusion of 1.0 µg/kg/min (maximum: 7.5 mg/hour) and a second 180 µg/kg bolus (maximum: 22.6 mg) administered 10 minutes after the first. In patients who undergo coronary artery bypass graft surgery, eptifibatide infusion should be discontinued prior to surgery.


Use the Cockcroft-Gault equation with actual body weight to calculate CRCL:

Males:
[(140 – age) x (actual body wt in kg) ]
----------------------------------------
72 x (serum creatinine)

Females:
[(140 – age) x (actual body wt in kg) x (0.85)]
----------------------------------------------
72 x (serum creatinine)

prasugrel - EFFIENT™ top of page

INDICATIONS AND USAGE
Acute Coronary Syndrome

Effient™ is indicated to reduce the rate of thrombotic cardiovascular (CV) events (including stent thrombosis) in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI) as follows:

--Patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI).
--Patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI.

Effient has been shown to reduce the rate of a combined endpoint of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke compared to clopidogrel. The difference between treatments was driven predominantly by MI, with no difference on strokes and little difference on CV death [see Clinical Studies (14) - package insert].

It is generally recommended that antiplatelet therapy be administered promptly in the management of ACS because many cardiovascular events occur within hours of initial presentation. In the clinical trial that established the efficacy of Effient, Effient and the control drug were not administered to UA/NSTEMI patients until coronary anatomy was established. For the small fraction of patients that required urgent CABG after treatment with Effient, the risk of significant bleeding was substantial [see Warnings and Precautions (5.2)]. Because the large majority of patients are managed without CABG, however, treatment can be considered before determining coronary anatomy if need for CABG is considered unlikely. The advantages of earlier treatment with Effient must then be balanced against the increased rate of bleeding in patients who do need to undergo urgent CABG.

DOSAGE AND ADMINISTRATION
Initiate Effient treatment as a single 60 mg oral loading dose and then continue at 10 mg orally once daily. Patients taking Effient should also take aspirin (75 mg to 325 mg) daily. Effient may be administered with or without food].

Dosing in Low Weight Patients
Compared to patients weighing geq 60 kg, patients weighing < 60 kg have an increased exposure to the active metabolite of prasugrel and an increased risk of bleeding on a 10 mg once daily maintenance dose. Consider lowering the maintenance dose to 5 mg in patients < 60 kg. The effectiveness and safety of the 5 mg dose have not been prospectively studied.

HOW SUPPLIED
Effient (prasugrel) 5 mg is supplied as a yellow, elongated hexagonal, film-coated, non-scored tablet debossed with "5 MG" on one side and with "4760" on the other side.

5 mg tablets are supplied as follows:
Bottles of 7 - NDC 0002-4760-76
Bottles of 30 - NDC 0002-4760-30

Effient (prasugrel) 10 mg is supplied as a beige, elongated hexagonal, film-coated, non-scored tablet debossed with "10 MG" on one side and "4759" on the other side.


10 mg tablets are supplied as follows:
Bottles of 30 – NDC 0002-4759-30
Blisters ID 90* NDC 0002-4759-77

ticagrelor -BRILINTA™ top of page

DESCRIPTION
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use BRILINTA safely and effectively. See full prescribing information for BRILINTA.

BRILINTA™ (ticagrelor) tablets, for oral use
Initial U.S. Approval: 2011

BRILINTA contains ticagrelor, a cyclopentyltriazolopyrimidine, inhibitor of platelet activation and aggregation mediated by the P2Y12 ADP-receptor.

INDICATIONS AND USAGE
Acute Coronary Syndromes
BRILINTA is a P2Y12 platelet inhibitor indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS) (unstable angina, non-ST elevation myocardial infarction, or ST elevation myocardial infarction). BRILINTA has been shown to reduce the rate of a combined endpoint of cardiovascular death, myocardial infarction or stroke compared to clopidogrel. The difference between treatments was driven by CV death and MI with no difference in stroke. In patients treated with PCI, it also reduces the rate of stent thrombosis.

BRILINTA has been studied in ACS in combination with aspirin. Maintenance doses of aspirin above 100 mg decreased the effectiveness of BRILINTA. Avoid maintenance doses of aspirin above 100 mg daily

DOSAGE AND ADMINISTRATION
Initiate BRILINTA treatment with a 180 mg (two 90 mg tablets) loading dose and continue treatment with 90 mg twice daily.

After the initial loading dose of aspirin (usually 325 mg), use BRILINTA with a daily maintenance dose of aspirin of 75-100 mg.

ACS patients who have received a loading dose of clopidogrel may be started on BRILINTA.

BRILINTA can be administered with or without food.

A patient who misses a dose of BRILINTA should take one 90 mg tablet (their next dose) at its scheduled time.

HOW SUPPLIED
BRILINTA (ticagrelor) 90 mg is supplied as a round, biconvex, yellow, film-coated tablet marked with a “90” above “T” on one side.

Bottles of 60 – NDC 0186-0777-60
Bottles of 180 – NDC 0186-0777-18
100 count Hospital Unit Dose – NDC 0186-0777-39

ticlopidine (Ticlid ®): top of page

 INDICATIONS:
--To reduce the risk of thrombotic stroke (fatal or nonfatal) in patients who have experienced stroke precursors, and in patients who have had a completed thrombotic stroke. Because TICLID is associated with a risk of life-threatening blood dyscrasias including thrombotic thrombocytopenic purpura (TTP), neutropenia/agranulocytosis and aplastic anemia, TICLID should be reserved for patients who are intolerant or allergic to aspirin therapy or who have failed aspirin therapy.

--As adjunctive therapy with aspirin to reduce the incidence of subacute stent thrombosis in patients undergoing successful coronary stent implantation.

DOSAGE AND ADMINISTRATION:
Stroke: The recommended dose of TICLID is 250 mg bid taken with food. Other doses have not been studied in controlled trials for these indications.

Coronary Artery Stenting: The recommended dose of TICLID is 250 mg bid taken with food together with antiplatelet doses of aspirin for up to 30 days of therapy following successful stent implantation.

Supplied:  250 mg tablet.

tirofiban (Aggrastat ®):  top of page

INDICATIONS AND USAGE:
AGGRASTAT is indicated to reduce the rate of thrombotic cardiovascular events (combined endpoint of death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS).

USE IN SPECIFIC POPULATIONS
Renal Insufficiency: Reduce the dose in patients with severe renal insufficiency.



DOSAGE AND ADMINISTRATION:

2.1 Recommended Dosage

The recommended dosage is 25 mcg/kg administered intravenously within 5 minutes and then 0.15 mcg/kg/min for up to 18 hours.

2.2 Administration

For intravenous use only. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not use plastic INTRAVIA bags in series connections; such use can result in air embolism by drawing air from the first bag if it is empty of solution.

To open the INTRAVIA bag, first tear off its foil overpouch. The plastic may be somewhat opaque because of moisture absorption during sterilization; the opacity will diminish gradually. Check for leaks by squeezing the inner bag firmly; if any leaks are found or sterility is suspect then the solution should be discarded. Do not use unless the solution is clear and the seal is intact.

Administration Instructions

Withdraw the bolus dose of AGGRASTAT from the 15 mL premixed bolus vial into a syringe. Alternatively, the bolus dose of AGGRASTAT may be administered from the 100 mL premixed vial or from the premixed bags. Do not dilute. Administer the bolus dose within 5 minutes via a syringe or IV pump.
Immediately following the bolus dose administration, administer the maintenance infusion from the 100 mL premixed vial or bags via an IV pump.
Discard any unused portion left in the vial or bag.

The recommended bolus volume using the 15 mL premixed bolus vial can be calculated using the following equation:

Bolus volume (mL) = [25 mcg/kg x body weight (kg)] / 250 mcg/mL

The recommended bolus volume using the 100 mL premixed vial or premixed bags can be calculated using the following equation:

Bolus volume (mL) = [25 mcg/kg x body weight (kg)] / 50 mcg/mL

The recommended infusion rate for patients with CrCl (Creatinine Clearance) >60 mL/min using the 100 mL premixed vial or premixed bags can be calculated using the following equation:

Infusion rate for CrCl > 60 mL/min (mL/hr) = [0.15 mcg/kg/min x body weight (kg) x 60 min/hr] / 50 mcg/mL


Drug Compatibilities
AGGRASTAT can be administered in the same intravenous line as heparin, atropine sulfate, dobutamine, dopamine, epinephrine hydrochloride (HCl), famotidine injection, furosemide, lidocaine, midazolam HCl, morphine sulfate, nitroglycerin, potassium chloride, and propranolol HCl. Do not administer AGGRASTAT through the same IV line as diazepam. Do not add other drugs or remove solution directly from the INTRAVIA bag with a syringe.

2.3 Dose Adjustment for Renal Impairment

The recommended dosage in patients with CrCl </=60 mL/min is 25 mcg/kg intravenously within 5 minutes and then 0.075 mcg/kg/min, for up to 18 hours.

The recommended infusion rate for patients with CrCl </=60 mL/min using the 100 mL premixed vial or premixed bags can be calculated using the following equation:

Infusion rate for CrCl </= 60 mL/min (mL/hr) = [0.075 mcg/kg/min x body weight (kg) x 60 min/hr] / 50 mcg/mL



DOSAGE FORMS AND STRENGTHS:
Injection: 5 mg/100mL (50 mcg/mL) in 100 mL bag
Injection: 12.5 mg/250mL (50 mcg/mL) in 250 mL bag
Injection: 5 mg/100mL (50 mcg/mL) in 100 mL vial
Injection: 3.75 mg/15mL (250 mcg/mL) in 15 mL bolus vial
 

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates.  A local search option of this data can be found here.

Disclaimer

Listed dosages are for - Adult patients ONLY. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. GlobalRPH does not directly or indirectly practice medicine or provide medical services and therefore assumes no liability whatsoever of any kind for the information and data accessed through the Service or for any diagnosis or treatment made in reliance thereon.

David F. McAuley, Pharm.D., R.Ph.  GlobalRPh Inc.
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