Prasugrel

373.44

373.44

1308068-626-2

B01AC22|B - Blood and blood forming organs

29349990

74.8

3.6

white to beige

1.347

120.0 to 124.0 °C

493.5±45.0 °C(Predicted)

252.3ºC

1.619

DMSO: >5mg/mL (warmed at 60 °C)

2-8°C

7.33X10-9 mm Hg at 25 deg C (est)

Henry's Law constant = 9.22X10-12 atm-cu m/mol at 25 °C (est)

MF: C20H20FN0SS.HCl. MW: 409.90. White to practically white solid. Soluble at pH 2, slightly soluble at pH 3 to 4, and practically insoluble at pH 6 to 7.5. Dissolves freely in methanol and is slightly soluble in 1- and 2-propanol and acetone. It is practically insoluble in diethyl ether and ethyl acetate. /Prasugrel hydrochloride/|Hydroxyl radical reaction rate constant = 1.33X10-10 cu cm/molecule-sec at 25 °C (est)

NONH for all modes of transport

3

24/25

P260, P264, P270, P273, P301+P312, P314, P330, P391, P501

H302

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including prasugrel hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Prasugrel hydrochloride/

|Danger|H302 (66.67%): Harmful if swallowed [Warning Acute toxicity, oral]|P260, P264, P270, P273, P301+P312, P307+P311, P314, P321, P330, P391, P405, and P501|Aggregated GHS information provided by 4 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

LD50 (rat) 1,000 - 2,000 mg/kg; LD50 (rabbit) > 1,000 mg/kg

Prasugrel is associated with low rates of serum enzyme elevations during therapy, which are similar to those with clopidogrel. In premarketing studies, no instances of clinically apparent liver injury were reported. Since marketing and release, there has been several reports of liver injury attributed to prasugrel often as a part of a hypersensitivity reaction. The onset was within a few weeks of switching from clopidogrel to prasugrel, and was accompanied by mild-to-moderate ALT and GGT elevations that resolved rapidly once prasugrel was replaced by clopidogrel. The liver injury was overshadowed by features of a hypersensitivity syndrome with fever, eosinophilia and diarrhea, which also reversed rapidly with stopping prasugrel. Autoantibodies were not reported. There has also been one report of a case of hepatocellular jaundice that resolved only after stopping prasugrel. There have been no reports of chronic injury or acute liver failure reported with prasugrel, although such instances have been reported with clopidogrel and ticlopidine.

Increased risk of bleeding in patients receiving concomitant therapy with warfarin. Bleeding time substantially prolonged with concomitant administration of a single 15-mg dose of warfarin.|Increased risk of bleeding with concomitant use /of thrombolytic agents/.|Increased risk of bleeding with concomitant long-term use of aspirin or other nonsteroidal anti-inflammatory agents (NSAIAs).|Prasugrel is metabolized by the cytochrome P-450 (CYP) microsomal enzyme system, principally by isoenzymes 3A4 and 2B6, and to a lesser extent by isoenzymes 2C9 and 2C19. In vitro studies indicate that prasugrel is not likely to inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2D6, and 3A or induce CYP isoenzymes 1A2 or 3A. Prasugrel is a weak inhibitor of CYP2B6. Clinically important drug interactions mediated by CYP isoenzymes are considered unlikely with prasugrel. Studies have shown that if one of the CYP isoenzymes involved in the metabolism of prasugrel is inhibited, others remain capable of forming the active metabolite. CYP3A4 inhibitors such as verapamil, diltiazem, indinavir, ciprofloxacin, clarithromycin, and grapefruit juice are not expected to have a substantial effect on the pharmacokinetics of prasugrel's active metabolite. In healthy individuals receiving prasugrel, concomitant administration of ketoconazole (a potent inhibitor of CYP3A4) decreased maximum concentrations of prasugrel's active metabolite by 34-46%, but did not alter systemic exposure or degree of inhibition of platelet aggregation. Similarly, CYP3A4 inducers (e.g., rifampin, carbamazepine) are not expected to substantially alter the pharmacokinetic or pharmacodynamic response to prasugrel; concomitant administration of rifampin, a potent inducer of CYP3A4 and CYP2B6, did not affect formation of the active prasugrel metabolite nor its ability to inhibit platelet aggregation. Concomitant administration of prasugrel and drugs principally metabolized by CYP2B6 (e.g., halothane, cyclophosphamide, propofol, nevirapine) may increase plasma concentrations and exposure of the concomitant drug; however, clinically important interactions are not expected because of weak inhibition of CYP2B6.|May be used concomitantly with proton pump inhibitors and histamine H2-receptor antagonists. Maximum plasma concentrations of the active metabolite of prasugrel are decreased by 14 or 29% with ranitidine or lansoprazole, respectively, but systemic exposure of this metabolite is unaffected. In a pharmacokinetic study in healthy adults, concomitant daily administration of a single loading dose of prasugrel 60 mg with lansoprazole 30 mg decreased systemic exposure and peak plasma concentrations of prasugrel's active metabolite but did not affect inhibition of platelet aggregation.

Geriatric patients, particularly those 75 years of age and older, appear to be at greater risk of bleeding (including fatal bleeding) with prasugrel therapy compared with younger patients. In the TRITON-TIMI 38 trial, about 39% of patients were 65 years of age or older and 13% were 75 years of age or older. Risk of bleeding increased with advancing age in both prasugrel and clopidogrel treatment groups. Among patients 75 years of age or older, fatal bleeding was more common with prasugrel than with clopidogrel (1 or 0.1%, respectively); symptomatic intracranial hemorrhage also was reported more frequently with prasugrel (0.8 or 0.3%, respectively). Mean exposure to the active metabolite of prasugrel is approximately 19% higher in patients 75 years or older compared with younger patients. Prasugrel generally should be avoided in patients 75 years of age or older because of a higher risk of bleeding and uncertain efficacy, but use may be considered in certain patients with high-risk conditions (e.g., diabetes, previous MI) in whom a greater net clinical benefit has been demonstrated.|Effient can cause significant, sometimes fatal, bleeding. Do not use Effient in patients with active pathological bleeding or a history of transient ischemic attack or stroke. In patients > or = 75 years of age, Effient is generally not recommended, because of the increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk situations (patients with diabetes or a history of prior myocardial infarction (MI)) where its effect appears to be greater and its use may be considered. Do not start Effient in patients likely to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue Effient at least 7 days prior to any surgery. Additional risk factors for bleeding include: body weight < 60 kg, propensity to bleed, concomitant use of medications that increase the risk of bleeding (e.g., warfarin, heparin, fibrinolytic therapy, chronic use of non-steroidal anti-inflammatory drugs [NSAIDS]). Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of Effient. If possible, manage bleeding without discontinuing Effient. Discontinuing Effient, particularly in the first few weeks after acute coronary syndrome, increases the risk of subsequent cardiovascular events.|Effient is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage

Approximately 98% of the active metabolite was bound to human serum albumin in a 4% buffered solution. The major inactive metabolites are also highly bound to human plasma proteins.

Indicated in combination with acetylsalicylic acid (ASA) to prevent atherothrombotic events in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI). May be used in patients with unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI) who are to be managed with PCI. Prasugrel is not recommended in patients 75 years of age or greater, those that weigh<60kg, and patients with a history of stroke or transient ischemic attack due to increased risk of fatal and intracranial bleeding.|FDA Label|Prasugrel Mylan, co administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with acute coronary syndrome (i.e. unstable angina, non-ST segment elevation myocardial infarction [UA/NSTEMI] or ST segment elevation myocardial infarction [STEMI]) undergoing primary or delayed percutaneous coronary intervention (PCI).|Efient, co-administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in patients with acute coronary syndrome (i.e. unstable angina, non-ST-segment-elevation myocardial infarction [UA / NSTEMI] or ST-segment-elevation myocardial infarction [STEMI]) undergoing primary or delayed percutaneous coronary intervention (PCI).,

Prasugrel is an inhibitor of platelet aggregation that is used to decrease the risk of myocardial infarction and stroke in patients with acute coronary syndromes. Prasugrel has been linked to mild and transient serum enzyme elevations during therapy and to rare instances of hypersensitivity reactions accompanied by mild liver injury.

Antithrombotic Agents

Purinergic P2Y Receptor Antagonists|Prasugrel hydrochloride is used in combination with aspirin for the reduction of thrombotic cardiovascular events (e.g., stent thrombosis, myocardial infarction in patients with acute coronary syndromes undergoing percutaneous coronary intervention. Prasugrel is used in patients with unstable angina or non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention and in patients with ST-segment elevation myocardial infarction managed with primary or nonprimary/delayed (i.e., after medical treatment for ST-segment elevation myocardial infarction) percutaneous coronary intervention. Because of established cardiovascular benefits, dual antiplatelet therapy with aspirin and prasugrel or clopidogrel is part of the current standard of care in patients with acute coronary syndromes. /Included in US product labeling/

/BOXED WARNING/ WARNING: BLEEDING RISK. Effient can cause significant, sometimes fatal, bleeding. Do not use Effient in patients with active pathological bleeding or a history of transient ischemic attack or stroke. In patients > or = 75 years of age, Effient is generally not recommended, because of the increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk situations (patients with diabetes or a history of prior myocardial infarction (MI)) where its effect appears to be greater and its use may be considered. Do not start Effient in patients likely to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue Effient at least 7 days prior to any surgery. Additional risk factors for bleeding include: body weight < 60 kg, propensity to bleed, concomitant use of medications that increase the risk of bleeding (e.g., warfarin, heparin, fibrinolytic therapy, chronic use of non-steroidal anti-inflammatory drugs [NSAIDS]). Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of Effient. If possible, manage bleeding without discontinuing Effient. Discontinuing Effient, particularly in the first few weeks after acute coronary syndrome, increases the risk of subsequent cardiovascular events.|Geriatric patients, particularly those 75 years of age and older, appear to be at greater risk of bleeding (including fatal bleeding) with prasugrel therapy compared with younger patients. In the TRITON-TIMI 38 trial, about 39% of patients were 65 years of age or older and 13% were 75 years of age or older. Risk of bleeding increased with advancing age in both prasugrel and clopidogrel treatment groups. Among patients 75 years of age or older, fatal bleeding was more common with prasugrel than with clopidogrel (1 or 0.1%, respectively); symptomatic intracranial hemorrhage also was reported more frequently with prasugrel (0.8 or 0.3%, respectively). Mean exposure to the active metabolite of prasugrel is approximately 19% higher in patients 75 years or older compared with younger patients. Prasugrel generally should be avoided in patients 75 years of age or older because of a higher risk of bleeding and uncertain efficacy, but use may be considered in certain patients with high-risk conditions (e.g., diabetes, previous MI) in whom a greater net clinical benefit has been demonstrated.|Thienopyridines, including prasugrel, should be discontinued prior to elective surgery. In patients who require elective coronary artery bypass grafting (CABG), discontinuance of prasugrel therapy is recommended at least 7 days prior to surgery. Prasugrel should not be initiated in those who are likely to undergo emergent CABG. To minimize the risk of adverse cardiac events, thienopyridines, including prasugrel, and other antiplatelet therapy should be resumed as soon as possible after temporary discontinuance of therapy for adverse effects or invasive procedures.|Safety and efficacy have not been established in pediatric patients.|For more Drug Warnings (Complete) data for Prasugrel (14 total), please visit the HSDB record page.

Prasugrel is a thienopyridine ADP receptor inhibitors which inhibits platelet aggregation by irreversibly binding to P2Y12 receptors.

Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. (See all compounds classified as Platelet Aggregation Inhibitors.)

79% or greater of the dose is absorbed after oral administration. Absorption and metabolism occur rapidly and peak plasma concentrations (C_max) are reached approximately 30 minutes following oral administration. Administration with a high fat, high calorie meal did not affect the AUC of the active metabolite in healthy individuals, but the C_max was decreased by ~49% and the T_max was increased to 0.5 to 1.5 hours. Prasugrel may be administered with or without food.|Approximately 68% of the orally administered dose is excreted in urine and 27% in the feces, as inactive metabolites. The active metabolite is not expected to be removed by dialysis.|44-68L|Apparent clearance = 112 - 166 L/hr|Tissue distribution of radioactivity related to prasugrel was studied in rats following single and repeated oral administration. Radioactivity was widely and rapidly distributed throughout the body. The radioactivity concentration was highest in most tissues involved in the absorption and elimination of the compound and its metabolites, i.e., stomach, intestines, liver, kidney and urinary bladder. Prasugrel distributed to the bone marrow of rats with a tissue-to-plasma ratio of less than 0.5. Following repeated daily dosing, accumulation consistent with the elimination half-life of prasugrel was observed in most organs.|Prasugrel is rapidly absorbed in all species including humans; Tmax of the active metabolite R-138727 is less than 1 hour. Prasugrel itself was not detected in plasma after oral administration. The decline of prasugrel related radioactivity was biphasic in rats and dogs. The radioactivity terminal elimination half-life seemed to be similar in mice and rats, approximately 24 hr, but it is considerably longer in dogs, approximately 3 days. In humans, the average terminal elimination half-life of the active metabolite R-138727 was approximately 7 hours. Approximately 21% of a (14)C-prasugrel dose is excreted in human feces within 48 hours.|In mice, 90% of the dose was excreted during the first 24 hours post dosing mainly via the urinary elimination route. In rats and dogs, the majority of the radioactivity (>90%) was excreted within the first 72 hours of dosing in faeces presumably via bile. Approximately 20% of the dose was excreted via urine. Radioactivity related to prasugrel was also detected in milk of lactating rats at concentrations up to approximately five times higher than the plasma level. However, the radioactivity from milk (half life =9.5 h) was eliminated more rapidly than that from the plasma (half life approximately 24 hr).|After a single oral dose of 5 mg/kg 14C-prasugrel to rats on Day 13 of pregnancy, the fetal concentration of prasugrel radioactivity was 0.27 times that in maternal blood 1 hour after administration and declined thereafter, suggesting low placental transfer of prasugrel or its metabolites.

Prasugrel is not detected in plasma following oral administration. It is rapidly hydrolyzed in the intestine to thiolactone by human carboxylesterase (hCE) 2. This intermediate is further metabolized to its active metabolite, R-138727, in a single step by cytochrome P450 enzymes in the liver (primarily CYP3A4 and CYP2B6 and to a lesser extent by CYP2C9 and CYP2C19). The active metabolite is further metabolized by S-methylation or cysteine conjugation to two inactive metabolites. Unlike clopidogrel, transformation of prasugrel to its active metabolite does not appear to be affected by cytochrome P450 polymorphisms.|Prasugrel was extensively metabolised in all species. A total of eighteen metabolites were identified in human plasma. Based on a mean radioactivity above 10%, the following major metabolites could be identified: diastereomers of M1, M2 (R-95913) and M5 (R-106583). The metabolites of prasugrel found in human plasma, urine and faeces were also detected in mouse, rat and dog; the only exception being M16, which was only identified in the mouse. M16 is M10 conjugated to glucuronic acid and M10 was found in all species. Furthermore, the extent of formation of a given metabolite varied significantly by species. Metabolite M1 was formed in large amounts in humans and was detected in animal plasma, but quantification was not conducted in animals due to co-eluting of the radioactive peaks. Metabolites M2, M5, M7 and M14 were also formed in larger amounts in humans as compared to the animal species.|Prasugrel is not detected in plasma following oral administration. It is rapidly hydrolyzed in the intestine to a thiolactone, which is then converted to the active metabolite by a single step, primarily by CYP3A4 and CYP2B6 and to a lesser extent by CYP2C9 and CYP2C19. The estimates of apparent volume of distribution of prasugrel's active metabolite ranged from 44 to 68 L and the estimates of apparent clearance ranged from 112 to 166 L/hr in healthy subjects and patients with stable atherosclerosis. The active metabolite is metabolized to two inactive compounds by S-methylation or conjugation with cysteine. The major inactive metabolites are highly bound to human plasma proteins. Approximately 68% of the prasugrel dose is excreted in the urine and 27% in the feces as inactive metabolites.|When administered at high doses ( > or = 100 mg/kg) to rats, prasugrel induced CYP450 enzymes (CYP2B and CYP3A2) and phase II metabolizing enzymes UDP-glucuronosyltransferase and glutathione- S-transferase, however, based on the in vitro non clinical study with human hepatocytes, this induction is not observed in humans. Furthermore, the AUC for each measured metabolite decreased after multiple dosing compared with the values obtained after the first dose in mice at > or = 100 mg/kg/day, in rats at 100 and 300 mg/kg/day, and in dogs at 20 mg/kg/day (after 20 weeks of dosing and beyond). However, the exposure data in dogs administered prasugrel at 20 mg/kg for one month were essentially unchanged. In the nine month study with dogs, the AUC data for two of the metabolites R-100932 and R-106583 decreased after 20 weeks of dosing, while the AUC values of the other metabolite, R-95913 were higher in dogs dosed with prasugrel at 20 mg/kg. Thus, the data show some auto-induction of prasugrel's metabolism at the 20-mg/kg dose in dogs.|Prasugrel ... undergoes rapid hydrolysis in vivo to a thiolactone, R-95913, which is further converted to its thiol-containing, pharmacologically active metabolite, R-138727, by oxidation via cytochromes P450 (P450). We trapped a sulfenic acid metabolite as a mixed disulfide with 2-nitro-5-thiobenzoic acid in an incubation mixture containing the thiolactone R-95913, expressed CYP3A4, and NADPH. Further experiments investigated one possible mechanism for the conversion of the sulfenic acid to the active thiol metabolite in vitro. A mixed disulfide form of R-138727 with glutathione was found to be a possible precursor of R-138727 in vitro when glutathione was present. The rate constant for the reduction of the glutathione conjugate of R-138727 to R-138727 was increased by addition of human liver cytosol to the human liver microsomes. Thus, one possible mechanism for the ultimate formation of R-138727 in vitro can be through formation of a sulfenic acid mediated by P450s followed possibly by a glutathione conjugation to a mixed disulfide and reduction of the disulfide to the active metabolite R-138727.

The active metabolite has an elimination half-life of about 7.4 hours (range 2-15 hours).|The radioactivity terminal elimination half-life seemed to be similar in mice and rats, approximately 24 hr, but it is considerably longer in dogs, approximately 3 days. In humans, the average terminal elimination half-life of the active metabolite R-138727 was approximately 7 hours. /R-138727/

Prasugrel is an thienopyridine and a prodrug which inhibits ADP receptors by irreversibly acting on the P2Y12 receptor on platelets. The active metabolite of prasugrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. Prasugrel is proposed to have a similar mechanism of action to clopidogrel.|The P2Y(12) receptor plays a crucial role in platelet aggregation and is the target of platelet aggregation inhibitors, including the thienopyridine compound prasugrel. The present study analyzed the effects of R-138727 (2-[1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-mercapto-3-piperidinylidene]acetic acid), the active metabolite of prasugrel, on recombinant wild-type and mutant human P2Y(12) receptors in order to identify the molecular site of action of R-138727. The function of wild-type and mutant P2Y(12) receptors stably expressed in Chinese hamster ovary cells was assessed by measuring the 2-methylthio-ADP-mediated inhibition of forskolin-stimulated cellular cAMP production. RESULTS: In cells expressing wild-type receptors, R-138727 potently inhibited receptor function with a half-maximal concentration below 1 uM. The mode of action was irreversible. The same effect of R-138727 was observed in cells expressing Cys17Ala/Cys270Ala constructs. In contrast, in cells expressing either a Cys97Ala construct or a Cys175Ala construct, R-138727 failed to inhibit the response to the agonist. When cells expressing wild-type receptors were pretreated with the P2 receptor antagonists ATP or suramin, no effect of R-138727 was observed. Similar experiments with N-acetylcysteine 10 uM showed no interference of N-acetylcysteine with R-138727. The experiments demonstrate a potent and irreversible action of R-138727 at the recombinant human P2Y(12) receptor. The data suggest that R-138727 interacts with cysteine 97 (upper portion of the predicted third transmembrane region) and cysteine 175 (second extracellular loop) of the receptor, which are likely to form a disulfide bridge in native receptors. Moreover, the data also suggest that this site of action of R-138727 is close to the ligand-binding site of the receptor. /R-138727/|Prasugrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Effient can cause significant, sometimes fatal, bleeding. Do not use Effient in patients with active pathological bleeding or a history of transient ischemic attack or stroke. In patients > or = 75 years of age, Effient is generally not recommended, because of the increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk situations (patients with diabetes or a history of prior myocardial infarction (MI)) where its effect appears to be greater and its use may be considered. Do not start Effient in patients likely to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue Effient at least 7 days prior to any surgery. Additional risk factors for bleeding include: body weight < 60 kg, propensity to bleed, concomitant use of medications that increase the risk of bleeding (e.g., warfarin, heparin, fibrinolytic therapy, chronic use of non-steroidal anti-inflammatory drugs [NSAIDS]). Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of Effient. If possible, manage bleeding without discontinuing Effient. Discontinuing Effient, particularly in the first few weeks after acute coronary syndrome, increases the risk of subsequent cardiovascular events.|/CASE REPORTS/ Therapy with aspirin and/or adenosine diphosphate (ADP) receptor blockers is associated with better outcomes via inhibition of platelet activity, and subsequent reduction of ischemic vascular events. Non-compliance is a well-recognized hazard limiting the clinical utility of antiplatelet agents, and, probably worsening outcomes. ... A 48-year-old male patient ... was among patients enrolled in the platelet sub-study for the /(Joint Utilization of Medication to Block Platelets Optimally (JUMBO)/ trial. He received 325 mg of aspirin daily for 9 months, presented with unstable angina for urgent coronary intervention, and was successfully reperfused with two intracoronary stents. The patient was randomised to a 60 mg prasugrel loading dose, and 10 mg of prasugrel daily for 30 days. Platelets were assessed at baseline, 4 and 24 hr, and at 30 days after acute coronary event utilising ADP-, and collagen-induced conventional aggregometry, rapid cartridge-based analyser and flow cytometry. Loading with prasugrel resulted in significant inhibition of platelet activity during and after stenting. However, after assessing platelet biomarkers at 30 days, voluntary withdrawal from the antiplatelet agents was suspected. Based on the platelet activity characteristics, non-compliance was later confirmed, and the patient admitted that he stopped taking both prasugrel and aspirin shortly after discharge due to minor bleeding episodes after shaving. Major platelet activity biomarkers of the index non-compliant patient were compared with those from compliant prasugrel-, clopidogrel-treated patients, and healthy controls. The platelet tests uniformly revealed rebound activation by all platelet measures (at least twofold increase) while being especially high for ADP-, and collagen-induced aggregation, platelet/endothelial cell adhesion molecule-1 (PECAM-1), glycoprotein (GP)Ib, GPIIb/IIIa activity, P-selectin, protease activated receptor (PAR)-1 thrombin receptor (activated and intact epitopes), and thrombospondin expression. The clinical benefits of antiplatelet agents are not only denied in non-compliant outpatients, but may put them at additional risk for worsened vascular outcomes due to the rebound platelet activation.

640315, LY

Oral: Tablets: 5 mg (of prasugrel), Effient, Eli Lilly and Company (also promoted by Daiichi Sankyo, Inc.); 10 mg (of prasugrel), Effient, Eli Lilly and Company (also promoted by Daiichi Sankyo, Inc.).

Human drugs -> Prasugrel Mylan -> EMA Drug Category|Antithrombotic agents -> Human pharmacotherapeutic group|Human drugs -> Efient -> EMA Drug Category|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients