Ticagrelor

522.574

522.57

1308068-626-2

GLH0314RVC

C76404

Crystalline powder

B01AC24|B - Blood and blood forming organs

2933990090

164

2

Solid

1.67

777.551°C at 760 mmHg

424.0±35.7 °C

1.744

6.30e-02 g/L

Keep container tightly closed in a dry and well-ventilated place.

1.21X10-20 mm Hg at 25 deg C (est)

24/25

Stable under recommended storage conditions.

P264, P273, P280, P305+P351+P338, P337+P313, P391, P501

H319

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.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material; Contaminated packaging: Dispose of as unused product.

Incompatible materials: Strong oxidizing agents

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

|Warning|H315 (11.11%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P273, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 18 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H315: Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Skin protection: Handle with gloves.|Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.|Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust; Environmental precautions: Do not let product enter drains; Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.|Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Patients experiencing an overdose may present with bleeding, nausea, vomiting, diarrhea, and ventricular pauses. Overdose can be managed through symptomatic and supportive treatment, including ECG monitoring. Dialysis is not expected to remove ticagrelor from the blood due to it being highly protein bound.|IDENTIFICATION AND USE: Ticagrelor is a crystalline powder. As the drug Brilinta, it is indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction (MI). Brilinta also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS. HUMAN EXPOSURE AND TOXICITY: Symptoms of overdose may include bleeding, gastrointestinal effects (nausea, vomiting and diarrhea) and ventricular pauses. Blood loss is the predominant risk. ANIMAL STUDIES: The acute toxicity of the drug is considered low. The results of single dose studies in mice and rats showed that ticagrelor was well tolerated when given orally by gavage at doses approximately 550 times the recommended human daily dose on a mg/kg basis. Repeat-dose studies were conducted in mice, rats and marmosets. Indications of subclinical bleeding were observed across species. Increased liver weight at high doses occurred in rodents. Ticagrelor had no effects on parturition or postnatal development in rats at doses up to 60 mg/kg/day (4.6 times the human therapeutic exposure), but did cause maternal and developmental toxicity in pups at 180 mg/kg. Ticagrelor given during the period of organogenesis had no effect on fetal development at oral doses up to 100 mg/kg/day in rats (5.1 times the human therapeutic exposure) and up to 42 mg/kg/day in rabbits (equivalent to the human therapeutic exposure). Ticagrelor and the active metabolite AR-C124910XX did not demonstrate any genotoxic potential in bacterial in vitro test, in vitro mouse lymphoma L5178Y TK+/- 3.7.2C cell, and in vivo rat bone marrow micronucleus assays.

In several large clinical trials, ticagrelor was not associated with serum enzyme elevations during therapy and no instances of clinically apparent liver injury were reported. While there have been isolated reports of transient and mild serum enzyme elevations during ticagrelor therapy, these have been short lived and asymptomatic. In addition, since marketing and release, there have been no reports of isolated clinically apparent liver injury or jaundice associated with ticagrelor therapy and hepatotoxicity is not mentioned in the product label. On the other hand, there have been several reports of jaundice and liver injury associated with rhabdomyolysis and with thrombotic thrombocytopenic purpura that represented secondary effects of these severe adverse events. Thus, significant liver injury due to ticagrelor occurs but has occurred largely in association with other life-threatening complications.

Concomitant administration of ticagrelor and digoxin did not substantially affect pharmacokinetics of digoxin; therefore, these drugs may be used concomitantly without dosage adjustments. However, because of the possibility of increased digoxin concentrations as a result of P-glycoprotein inhibition, serum digoxin concentrations should be monitored during initiation of and following any change in ticagrelor therapy.|When ticagrelor is used in conjunction with aspirin maintenance dosages exceeding 100 mg daily, efficacy of ticagrelor may be reduced.|Ticagrelor is a substrate and weak inhibitor of the P-glycoprotein transport system. Increased serum concentrations of P-glycoprotein substrates (e.g., digoxin) are possible when these drugs are used concomitantly with ticagrelor; appropriate laboratory and/or clinical monitoring is recommended.|Concomitant administration of ticagrelor and rifampin 600 mg once daily substantially decreased peak plasma concentrations of and systemic exposure to ticagrelor. Concomitant use of ticagrelor and rifampin should therefore be avoided.|For more Interactions (Complete) data for Ticagrelor (9 total), please visit the HSDB record page.

Brilinta is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage.|Brilinta is contraindicated in patients with a history of intracranial hemorrhage (ICH) because of a high risk of recurrent ICH in this population.|Ticagrelor is metabolized by the liver and impaired hepatic function can increase risks for bleeding and other adverse events. Avoid use of Brilinta in patients with severe hepatic impairment. There is limited experience with Brilinta in patients with moderate hepatic impairment; consider the risks and benefits of treatment, noting the probable increase in exposure to ticagrelor.

Ticagrelor and its active metabolite ate >99% protein bound in plasma, particularly albumin.

A Kd value of 1,571 was measured using an activated sewage sludge from the Tontes wastewater treatment plant in Devon, UK(1).

Ticagrelor is indicated to reduce the risk of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome or a history of myocardial infarction. Ticagrelor is also indicated to reduce the risk of a first myocardial infarction or stroke in high risk patients with coronary artery disease.|FDA Label|Brilique, co administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients withacute coronary syndromes (ACS) ora history of myocardial infarction (MI) and a high risk of developing an atherothrombotic eventBrilique, co-administered with acetyl salicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with a history of myocardial infarction (MI occurred at least one year ago) and a high risk of developing an atherothrombotic event.|Possia, co-administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with acute coronary syndromes (unstable angina, non-ST-elevation myocardial infarction [NSTEMI] or ST-elevation myocardial infarction [STEMI]); including patients managed medically, and those who are managed with percutaneous coronary intervention (PCI) or coronary artery by-pass grafting (CABG).|Prevention of thromboembolic events

Ticagrelor is an oral antiplatelet drug that is used with low dose aspirin to decrease the risk of myocardial infarction and stroke in patients with acute coronary syndromes. Ticagrelor has been linked to rare instances of hypersensitivity reactions accompanied by mild liver injury.

Antithrombotic Agents

Purinergic P2Y Receptor Antagonists|/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Ticagrelor is included in the database.|Brilinta is indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction (MI). For at least the first 12 months following ACS, it is superior to clopidogrel. /Included in US product label/|Brilinta also reduces the rate of stent thrombosis in patients who have been stented for treatment of acute coronary syndrome (ACS). /Included in US product label/

/BOXED WARNING/ BLEEDING RISK. Brilinta, like other antiplatelet agents, can cause significant, sometimes fatal bleeding. Do not use Brilinta in patients with active pathological bleeding or a history of intracranial hemorrhage. Do not start Brilinta in patients undergoing urgent coronary artery bypass graft surgery (CABG). If possible, manage bleeding without discontinuing Brilinta. Stopping Brilinta increases the risk of subsequent cardiovascular events|/BOXED WARNING/ ASPIRIN DOSE AND BRILINTA EFFECTIVENESS. Maintenance doses of aspirin above 100 mg reduce the effectiveness of Brilinta and should be avoided.|In general, treatment with ticagrelor should not be discontinued prematurely because this increases the risk of cardiovascular events. Premature discontinuance of antiplatelet therapy (e.g., P2Y12 adenosine diphosphate (ADP)-receptor antagonists, aspirin) in patients with coronary artery stents has been associated with an increased risk of ischemic cardiovascular events (e.g., stent thrombosis, myocardial infarction (MI), death). If temporary discontinuance of ticagrelor is necessary such as prior to elective surgery or for management of bleeding, the drug should be restarted as soon as possible. Patients should be advised to never stop taking ticagrelor without first consulting the prescribing clinician, even if instructed by another clinician (e.g., dentist) to stop such therapy. Prior to scheduling an invasive procedure, patients should inform clinicians (including dentists) that they are currently taking ticagrelor and clinicians performing the invasive procedure should consult with the prescribing clinician before discontinuing such therapy.|Bradyarrhythmias, including ventricular pauses, have occurred in patients receiving ticagrelor. In the The Study of Platelet Inhibition and Patient Outcomes (PLATO) study, Holter monitor-detected ventricular pauses of at least 3 seconds were reported more frequently during the first week of therapy in patients receiving ticagrelor than in those receiving clopidogrel (5.8 versus 3.6%, respectively). There was no difference in the overall risk of clinically important bradycardic effects (e.g., syncope, need for pacemaker insertion) between the treatment groups. Ventricular pauses were mostly asymptomatic and attributed to sinoatrial nodal suppression. Patients with a baseline increased risk of bradycardia (e.g., those with sick sinus syndrome, second- or third-degree AV block, syncope due to bradycardia without a pacemaker) were excluded from the PLATO study; therefore, some clinicians recommend that ticagrelor be used with caution in such patients.|For more Drug Warnings (Complete) data for Ticagrelor (15 total), please visit the HSDB record page.

Ticagrelor is a P2Y₁₂ receptor antagonist that inhibits the formation of thromboses to reduce the risk of myocardial infarction and ischemic stroke. It has a moderate duration of action as it is given twice daily, and a wide therapeutic index as high single doses are well tolerated. Patients should be counselled regarding the risk of bleeding, dyspnea, and bradyarrhythmias.

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.)|Compounds that bind to and block the stimulation of PURINERGIC P2Y RECEPTORS. Included under this heading are antagonists for specific P2Y receptor subtypes. (See all compounds classified as Purinergic P2Y Receptor Antagonists.)

Ticagrelor is 36% orally bioavailable. A single 200mg oral dose of ticagrelor reaches a C_max of 923ng/mL, with a T_max of 1.5 hours and an AUC of 6675ng\*h/mL. The active metabolite of ticagrelor reaches a C_max of 264ng/mL, with a T_max of 3.0 hours and an AUC of 2538ng\*h/mL.|A radiolabelled dose of ticagrelor is 57.8% recovered in feces and 26.5% recovered in urine. Less than 1% of the dose is recovered as the unmetabolized parent drug. The active metabolite AC-C124910XX makes up 21.7% of the recovery in the feces. The metabolite AR-C133913XX makes up 9.2% of the recovery in the urine and 2.7% of the recovery in the feces. Other minor metabolites are predominantly recovered in the urine.|The steady state volume of distribution of ticagrelor is 88 L.|The renal clearance of ticagrelor is 0.00584L/h.|The drug is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A4 to an active metabolite that has similar antiplatelet activity as the parent drug.Plasma concentrations of ticagrelor and its active metabolite increase in a dose-dependent manner with peak concentrations achieved within approximately 1.5 and 2.5 hours, respectively. Ticagrelor is primarily eliminated in the feces and to a lesser extent in urine; less than 1% of a dose is recovered in urine as the parent drug and active metabolite. ... Both ticagrelor and its active metabolite are extensively (more than 99%) bound to human plasma proteins. Administration with a high-fat meal increases systemic exposure of ticagrelor by 21% and decreases peak plasma concentrations of the active metabolite by 22%, but has no effect on peak plasma concentrations of ticagrelor or on systemic exposure to the active metabolite.|Ticagrelor is rapidly absorbed following oral administration.|The primary route of ticagrelor elimination is hepatic metabolism. When radiolabeled ticagrelor is administered, the mean recovery of radioactivity is approximately 84% (58% in feces, 26% in urine). Recoveries of ticagrelor and the active metabolite in urine were both less than 1% of the dose. The primary route of elimination for the major metabolite of ticagrelor is most likely to be biliary secretion.|/MILK/ It is not known whether ticagrelor or its active metabolites are excreted in human milk. Ticagrelor is excreted in rat milk.|For more Absorption, Distribution and Excretion (Complete) data for Ticagrelor (6 total), please visit the HSDB record page.

The complete structure of all ticagrelor metabolites are not well defined. Ticagrelor can be dealkylated at postition 5 of the cyclopentane ring to form the active AR-C124910XX. AR-C124910XX's cyclopentane ring can be further glucuronidated or the alkyl chain attached to the sulfur can be hydroxylated. Ticagrelor can also be glucuronidated or hydroxylated. Ticagrelor can also be N-dealkylated to form AR-C133913XX, which is further glucuronidated or hydroxylated.|CYP3A4 is the major enzyme responsible for ticagrelor metabolism and the formation of its major active metabolite. Ticagrelor and its major active metabolite are weak P-glycoprotein substrates and inhibitors. The systemic exposure to the active metabolite is approximately 30-40% of the exposure of ticagrelor.|The drug is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A4 to an active metabolite that has similar antiplatelet activity as the parent drug.|Ticagrelor is a reversibly binding oral P2Y(12) receptor antagonist in development for the prevention of thrombotic events in patients with acute coronary syndromes. The pharmacokinetics, metabolism, and excretion of ticagrelor were investigated over 168 hr in six healthy male subjects receiving a single oral suspension dose of 200 mg of (14)C-ticagrelor. ... Major circulating components in the plasma and feces were identified as ticagrelor and AR-C124910XX, whereas in urine the major components were metabolite M5 (AR-C133913XX) and its glucuronide conjugate M4. Levels of unchanged ticagrelor and AR-C124910XX were <0.05% in the urine, indicating that renal clearance of ticagrelor and AR-C124910XX is of minor importance. Interindividual variability was small in both urine and fecal extracts with only small quantitative differences. All 10 of the metabolites were fully or partially characterized and a full biotransformation pathway was proposed for ticagrelor, in which oxidative loss of the hydroxyethyl side chain from ticagrelor forms AR-C124910XX and a second oxidative pathway leads to N-dealkylation of ticagrelor, forming AR-C133913XX.

Ticagrelor has a plasma half life of approximately 8 hours, while the active metabolite has a plasma half life of approximately 12 hours.|The mean terminal half-lives of ticagrelor and its active metabolite reportedly are about 7 and 9 hours, respectively.|Ticagrelor is a reversibly binding oral P2Y(12) receptor antagonist in development for the prevention of thrombotic events in patients with acute coronary syndromes. The pharmacokinetics, metabolism, and excretion of ticagrelor were investigated over 168 hr in six healthy male subjects receiving a single oral suspension dose of 200 mg of (14)C-ticagrelor. In most subjects, radioactivity was undetectable in plasma after 20 hr and whole blood after 12 hr (half-life values of 6.3 and 4.6 hr, respectively).

Ticagrelor is a P2Y₁₂ receptor antagonist. The P2Y₁₂ receptor couples with Gα_i2 and other G_i proteins which inhibit adenylyl cyclase. G_i mediated signalling also activates PI3K, Akt, Rap1b, and potassium channels. The downstream effects of these activities mediate hemostasis and lead to platelet aggregation. Antagonism of the P2Y₁₂ receptor reduces development of occlusive thromboses, which can reduce the risk of myocardial infarction and ischemic stroke.|Ticagrelor, a cyclopentyltriazolopyrimidine derivative, is a nonthienopyridine, P2Y12 platelet adenosine diphosphate (ADP)-receptor antagonist. In contrast to the thienopyridines (e.g., clopidogrel, prasugrel), ticagrelor binds reversibly to the P2Y12 ADP receptor and does not require hepatic transformation to exert its pharmacologic effect. Ticagrelor exhibits noncompetitive and reversible binding to the P2Y12 platelet ADP receptor, preventing signal transduction of the cyclic adenosine monophosphate (cAMP) pathway. This results in reduced exposure of fibrinogen binding sites to the platelet glycoprotein (GP) IIb/IIIa complex and subsequent inhibition of platelet activation and aggregation. In addition to platelet ADP-receptor blockade, ticagrelor inhibits reuptake of adenosine into erythrocytes, a mechanism that may account for some of the beneficial cardiovascular effects of the drug, while potentially contributing to some of its adverse effects (e.g., dyspnea, ventricular pauses).

Ticagrelor is a direct-acting reversibly binding P2Y12 antagonist and is widely used as an antiplatelet therapy for the prevention of cardiovascular events in acute coronary syndrome patients. However, antiplatelet therapy can be associated with an increased risk of bleeding. Here, we present data on the identification and the in vitro and in vivo pharmacology of an antigen-binding fragment (Fab) antidote for ticagrelor. The Fab has a 20 pM affinity for ticagrelor, which is 100 times stronger than ticagrelor's affinity for its target, P2Y12. Despite ticagrelor's structural similarities to adenosine, the Fab is highly specific and does not bind to adenosine, adenosine triphosphate, adenosine 5'-diphosphate, or structurally related drugs. The antidote concentration-dependently neutralized the free fraction of ticagrelor and reversed its antiplatelet activity both in vitro in human platelet-rich plasma and in vivo in mice. Lastly, the antidote proved effective in normalizing ticagrelor-dependent bleeding in a mouse model of acute surgery. This specific antidote for ticagrelor may prove valuable as an agent for patients who require emergency procedures.|/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 TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) 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/ Bleeding is the expected pharmacologic effect of overdosing. If bleeding occurs, appropriate supportive measures should be taken. Other effects of overdose may include gastrointestinal effects (nausea, vomiting, diarrhea) or ventricular pauses. Monitor the ECG.|/SIGNS AND SYMPTOMS/ Like other antiplatelet agents, ticagrelor increases the risk of bleeding, which may be serious and sometimes fatal.|/EPIDEMIOLOGY STUDIES/ /The purpose of this study was/ to evaluate the effect of Ticagrelor on intra- and postoperative bleeding complications in patients undergoing coronary bypass surgery. For this study, patients who underwent on-pump or off-pump coronary bypass surgery with preoperative acetylsalicylic acid (ASA) and Ticagrelor administration, between January 2014 and December 2014, were included. In the matched control group, continued dual antiplatelet therapy (DAPT) consisted of Clopidogrel and ASA. A total of 28 consecutive patients (24 males; 73 + or - 6.6 years) with preoperative Ticagrelor intake underwent elective (n = 22), urgent (n = 2) or emergency (n = 4) cardiac bypass surgery. The postoperative blood loss, red blood cell units given and intra- and postoperative bleeding complications were documented. To evaluate the effect of Ticagrelor treatment on bleeding during and after coronary bypass surgery in a non-randomized study, we used a case-matched analysis. Baseline parameters showed no important differences between the study group and the control group regarding the matching variables, left ventricular function, preoperative clinical status and risk stratification. The preoperative laboratory analysis showed no important differences regarding coagulation and blood cell count parameters. Overall blood loss was significantly higher in the study group with a mean loss of 1028.8 + or - 735.5 mL (P = 0.0002). Accordingly, units of red blood cells administered were also significantly higher in the study group (P = 0.0002). In the Ticagrelor group, there were six rethoracotomies due to postoperative bleeding with a blood loss of more than 1200 mL in the first 3 hr. With no rethoracotomies in the Clopidogrel group, this also showed statistical significance for the postoperative course (P = 0.02). There were no differences found regarding ICU stay and ventilation time. Comparing the mean hospital stay, the study group presented a significantly longer stay than the control group (P = 0.001). Recent studies about bleeding complications in patients with Ticagrelor intake undergoing coronary artery bypass grafting (CABG) in a real-life scenario presented inconsistent data. We were able to show in a case-matched analysis that Ticagrelor administration leads to significantly higher blood loss, more red blood cell units transfused and a higher rate of rethoracotomies. The data also present a longer hospital stay to the disadvantage of the study group. Consequently, Ticagrelor intake before CABG procedures should be avoided or at least discontinued 3 days before cardiac surgery.|/EPIDEMIOLOGY STUDIES/ Ticagrelor (Brilique) is a novel reversible platelet inhibitor at P2Y12 receptor used in patients with acute coronary syndrome and patients undergoing percutaneous coronary interventions. Unlike clopidogrel (Plavix), ticagrelor has a quicker offset of action, and therefore, it seems that platelet function recovers faster on discontinuation of therapy. These drugs sometimes cannot be stopped before coronary artery bypass grafting due to the risk of stent thrombosis or in case of emergency operations. Therefore, we investigated whether the continued preoperative use of ticagrelor influences the perioperative course of cardiac surgical patients. The perioperative course and clinical outcomes of patients preoperatively receiving ticagrelor + acetylsalicylic acid (ASA) (n = 32) or clopidogrel + ASA (n = 49) until cardiac surgery, performed at University of Goettingen between January 2012 and December 2012, were studied. The study was designed as a retrospective observational study. The observation period started with the surgery and ended after 3 days. P < 0.05 was considered statistically significant. Preoperative data and intraoperative characteristics were almost similar among the groups. In the first 24 hr, the median blood loss was 850 [780-1600] mL in the ticagrelor group and 680 [400-860] mL in the clopidogrel group (P = 0.0006). Furthermore, the median red blood cell transfusion (P = 0.0031), the median pooled platelet transfusion (P = 0.0012), the median prothrombin complex concentrate use (P = 0.0114) and the median fibrinogen use (P = 0.0118) were significantly higher in the ticagrelor group compared with the clopidogrel group. However, there was no statistical significance between the two groups regarding intensive care unit and hospital stay, mechanical ventilation time, incidence of acute kidney injury and mortality. Hence, a tendency towards more rethoracotomies due to bleeding in the ticagrelor group was observed (P = 0.0632). In cardiac surgical patients who are treated with ticagrelor + ASA until surgery, ticagrelor therapy is associated with a significantly higher blood loss, a significantly higher use of blood products and coagulation factors and higher incidence of rethoracotomies for bleeding compared with patients treated with clopidogrel + ASA.|For more Human Toxicity Excerpts (Complete) data for Ticagrelor (6 total), please visit the HSDB record page.

3-(7-((2-(3,4-difluorophenyl)cyclopropyl)amino)-5-(propylthio)-3H-(1-3)-triazolo(4,5-d)pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol

Oral: Tablets: 90 mg, Brilinta (AstraZeneca)

Human drugs -> Brilique -> EMA Drug Category|Antithrombotic agents -> Human pharmacotherapeutic group|Human drugs -> Possia -> EMA Drug Category|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients