Platelet Aggregation Inhibitor Ticagrelor(274693-27-5) for sale

1. www.aasraw.com Platelet Aggregation Inhibitor Ticagrelor(274693-27-5) For Sale Platelet Aggregation Inhibitor Ticagrelor(274693-27-5) For Sale.......................................................1 1. Ticagrelor(274693-27-5)..................................................................................................................1 2. Ticagrelor Brand Name: Brilinta................................................................................................2 3. Ticagrelor: Mechanism Of Action....................................................................................................3 4. How does ticagrelor(Brilinta) work?...............................................................................................5 5. Ticagrelor--Clinical Trials..................................................................................................................5 (1) Clinical efficacy of Ticagrelor.................................................................................................5 (2) Conclusion..............................................................................................................................6 6. What is the drug ticagrelor used for?.............................................................................................9 7. How to take Ticagrelor(Brilinta) reasonably?................................................................................. 9 (1) Ticagrelor(Brilinta) dosing information................................................................................. 9 (2) How is this Ticagrelor best taken?.......................................................................................11 (3) How should I take ticagrelor (Brilinta)?...............................................................................13 (4) What should I avoid while taking ticagrelor(Brilinta)?........................................................14 8. Ticagrelor Side Effects................................................................................................................... 14 9. What other drugs will affect ticagrelor?.......................................................................................16 10. What should I know about storage and disposal of this medication?.......................................17 11. What is the most important information I should know about ticagrelor (Brilinta)?................18 12. Where can I get more information?............................................................................................20 1. Ticagrelor(274693-27-5) Ticagrelor (trade name Brilinta in the US, Brilique and Possia in the EU) is a platelet aggregation inhibitor produced by AstraZeneca. Unlike clopidogrel, ticagrelor is not a prodrug and does not require metabolic activation. Ticagrelor is used along with aspirin to prevent serious or life-threatening problems with the heart and blood vessels in people who 1 aas11@aasraw.com

2. www.aasraw.com have had a heart attack or severe chest pain. It is also used to prevent blood clots from forming in people with coronary stents (metal tubes surgically placed in clogged blood vessels to improve blood flow) who have had a heart attack or severe chest pain. Ticagrelor is in a class of medications called antiplatelet medications. It works by preventing platelets (a type of blood cell) from collecting and forming clots that may cause a heart attack or stroke. 2. Ticagrelor Brand Name: Brilinta Ticagrelor is a crystalline powder with an aqueous solubility of approximately 10 mcg/mL at room temperature. 2 aas11@aasraw.com

3. www.aasraw.com Brilinta tablets for oral administration contain 90 mg of ticagrelor and the following ingredients: mannitol, dibasic calcium phosphate, sodium starch glycolate, hydroxypropyl cellulose, magnesium stearate, hydroxypropyl methylcellulose, titanium dioxide, talc, polyethylene glycol 400, and ferric oxide yellow. 3. Ticagrelor: Mechanism Of Action Ticagrelor(Brilinta), a member of the new chemical class cyclopentyltriazolopyrimidines (CPTP), which is a oral, direct acting, selective and reversibly binding P2Y12 receptor antagonist that prevents adenosine diphosphate (ADP)-mediated P2Y12 platelet activation and aggregation. 3 aas11@aasraw.com

4. www.aasraw.com Ticagrelor does not prevent ADP binding, but when bound to the P2Y12 receptor prevents ADP-induced signal transduction. Since platelets participate in the initiation and/or evolution of thrombotic complications of atherosclerotic disease, inhibition of platelet function has been shown to reduce the risk of cardiovascular events such as death, myocardial infarction or stroke. Ticagrelor has an additional mechanism of action, increasing local endogenous adenosine levels by inhibiting equilibrative nucleoside transporter-1 (ENT-1). Adenosine is formed locally at sites of hypoxia and tissue damage through degradation of released adenosine tri- and di-phosphate (ATP and ADP). As adenosine degradation is essentially restricted to the intracellular space, inhibition of ENT-1 by ticagrelor prolongs the half-life of adenosine and thereby increases its local extracellular concentration providing enhanced local adenosine responses. Ticagrelor has no clinically significant direct effect on adenosine receptors (A1, A2A, A2B, A3) and is not metabolised to adenosine. Adenosine has been documented to have a number of effects that include: vasodilation, cardioprotection, platelet inhibition, modulation of inflammation and induction of dyspnoea, which may contribute to the clinical profile of ticagrelor. 4 aas11@aasraw.com

5. www.aasraw.com 4. How does ticagrelor(Brilinta) work? Ticagrelor(Brilinta)reversibly inhibits the platelet adenosine diphosphate (ADP) P2Y12 receptors which results in rapid inhibition of platelet activation and aggregation. Clopidogrel also acts on these receptors, however, because it is a “prodrug”, the transformation to the active metabolite tends to result in slower and less consistent inhibition of platelets than with ticagrelor(Brilinta).3, 5 The transformation of clopidogrel to its active metabolite requires the enzyme CYP2C19. Approximately 30–40% of people of M ā ori, Pacific and Asian ethnicity have reduced function CYP2C19 polymorphisms, compared to 15% of Europeans. Although it is not yet proven, ticagrelor(Brilinta) may be of particular benefit, compared with clopidogrel, for people in these ethnic groups (Māori, Pacific and Asian). 5. Ticagrelor--Clinical Trials (1) (1) Clinical Clinical efficacy efficacy of of Ticagrelor Ticagrelor The efficacy and safety of ticagrelor have been evaluated by Platelet inhibition and Patient Outcomes (PLATO) phase-III trial. The PLATO trial was performed in patients with either non-ST elevation or ST-elevation ACS. A total of 18,624 patients were randomly assigned to receive either ticagrelor 5 aas11@aasraw.com

6. www.aasraw.com (180 mg loading dose, 90 mg twice daily thereafter) or clopidrogel (300-600 mg loading dose, 75 mg thereafter) along with aspirin (75-100 mg per day) for 12 months. The primary efficacy outcome was the death from cardiovascular causes. Myocardial infarction or stroke was significantly reduced among patients who received ticagrelor compared with those who took clopidrogel (9.8% versus 11.7%; hazard ratio (HR) 0.84, P < 0.001). However, one group of patients enrolled in United States fared worse with ticagrelor as compared of clopidrogel (hazard ratio 1.27 as compared to hazard ratio for non US patients: 0.81). PLATO data showed that aspirin dosage was ≥300 mg in this subgroup of patients and that might be reason for this type of response. (2) (2) Conclusion Conclusion In view of the overall health impact of ACS, as well as its significant economic burden, P&T decision makers need to identify optimal treatment approaches to this debilitating and potentially fatal disorder. Ticagrelor(Brilinta) is the first cyclopentyltriazolopyridine in a new class of antiplatelets. Ticagrelor interacts with the P2Y12 ADP receptor, which is 6 aas11@aasraw.com

7. www.aasraw.com approved for the reduction of thrombotic cardiovascular events in patients with ACS. Ticagrelor is not a prodrug and does not require metabolic activation to inhibit the P2Y12 receptor; however, hepatic metabolism is needed to produce its active metabolite. In the pivotal phase-3 PLATO trial, Ticagrelor(Brilinta) significantly reduced the rate of first occurrence of the study ’ s composite end point of cardiovascular death, nonfatal MI (excluding silent MI), or stroke versus clopidogrel. Ticagrelor also reduced the secondary end points of cardiovascular death and MI individually, with no difference in stroke versus clopidogrel. 7 aas11@aasraw.com

8. www.aasraw.com Ticagrelor(Brilinta) has been studied in ACS in combination with aspirin. Maintenance doses of aspirin above 100 mg decreased the effectiveness of Ticagrelor. Maintenance doses of aspirin above 100 mg should be avoided. Like other antiplatelet agents, Ticagrelor can cause significant, sometimes fatal, bleeding. Ticagrelor should not be used in patients with active pathological bleeding or a history of intracranial hemorrhage. Ticagrelor should not be started in patients planned to undergo urgent CABG surgery. When possible, discontinue Ticagrelor at least 5 days prior to any surgery. Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, PCI, CABG, or other surgical procedures in the setting of Ticagrelor. If possible, manage bleeding without discontinuing Ticagrelor. Stopping Ticagrelor increases the risk of subsequent cardiovascular events. Ticagrelor(Brilinta) is contraindicated in patients with a history of intracraial hemorrhage and active pathological bleeding, such as peptic ulcer. Ticagrelor is also contraindicated in patients with severe hepatic impairment because of a probable increase in exposure. Ticagrelor has not been studied in these patients. Severe hepatic impairment increases the risk of bleeding because of reduced synthesis of coagulation proteins. 8 aas11@aasraw.com

9. www.aasraw.com The clinical use of Ticagrelor is supported by a Risk Evaluation and Mitigation Strategy (REMS) initiative, which is designed to inform health care professionals and patients about the risks associated with Ticagrelor, particularly the risk of bleeding, and about the need to ensure that the maintenance dose of aspirin, co-administered with Ticagrelor, does not exceed 100 mg. 6. What is the drug ticagrelor used for? ♦ Ticagrelor use: It is used to lower the chance of heart attack, stroke, and death in some people. ♦ Ticagrelor use: It is used to lower the chance of blockage of a stent after a stent is placed in the heart. ♦ Ticagrelor use: It may be given to you for other reasons. Talk with the doctor. 7. How to take Ticagrelor(Brilinta) reasonably? (1) (1) Ticagrelor(Brilinta) Ticagrelor(Brilinta) dosing dosing information information 9 aas11@aasraw.com

10. www.aasraw.com Usual Adult Dose for Acute Coronary Syndrome: Following an acute coronary syndrome (ACS) event: Loading dose: 180 mg orally once Maintenance dose: 90 mg orally twice a day for 1 year Maintenance dose after 1 year: 60 mg orally twice a day Comments: -This drug should be taken in conjunction with a daily maintenance dose of aspirin 75 to 100 mg orally once a day. -For at least the first 12 months following ACS, this drug is superior to clopidogrel. Uses: -To reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction. -To reduce the rate of stent thrombosis in patients who have been stented for treatment of ACS. 10 aas11@aasraw.com

11. www.aasraw.com Usual Adult Dose for Prevention of Atherothrombotic Events: Following an acute coronary syndrome (ACS) event: Loading dose: 180 mg orally once Maintenance dose: 90 mg orally twice a day for 1 year Maintenance dose after 1 year: 60 mg orally twice a day Comments: -This drug should be taken in conjunction with a daily maintenance dose of aspirin 75 to 100 mg orally once a day. -For at least the first 12 months following ACS, this drug is superior to clopidogrel. Uses: -To reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction. -To reduce the rate of stent thrombosis in patients who have been stented for treatment of ACS. (2) (2) How How is is this this Ticagrelor Ticagrelor best best taken? taken? 11 aas11@aasraw.com

12. www.aasraw.com Use ticagrelor as ordered by your doctor. Read all information given to you. Follow all instructions closely. ♦ Take ticagrelor at the same time of day. ♦ Take with or without food. ♦ If you cannot swallow the tablet whole, the tablet can be crushed and mixed with water. ♦ Drink right away after mixing. Refill the glass with water, stir, and drink. ♦Those who have feeding tubes may use the tablet. Crush the tablet and mix it with water. ♦ Flush the feeding tube after ticagrelor is given. ♦ To gain the most benefit, do not miss doses. ♦ Keep taking ticagrelor as you have been told by your doctor or other health care provider, even if you feel well. What do I do if I miss a ticagrelor dose? ♦ Skip the missed ticagrelor dose and go back to your normal time. ♦ Do not take 2 ticagrelor doses at the same time or extra doses. 12 aas11@aasraw.com

13. www.aasraw.com (3) (3) How How should should I I take take ticagrelor ticagrelor (Brilinta)? (Brilinta)? Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Ticagrelor should be taken together with aspirin. Follow your doctor's instructions about how much aspirin you should take. Ticagrelor can be taken with or without food. Take the medicine at the same time each day. Because ticagrelor keeps your blood from coagulating (clotting) to prevent unwanted blood clots, this medicine can also make it easier for you to bleed, even from a minor injury. Contact your doctor or seek emergency medical attention if you have any bleeding that will not stop. If you need surgery or dental work, tell the surgeon or dentist ahead of time that you are using ticagrelor. You may need to stop using the medicine for at least 5 days before having surgery, to prevent excessive bleeding. Follow your doctor's instructions and start taking ticagrelor again as soon as possible. Do not stop taking ticagrelor without first talking to your doctor, even if you have signs of bleeding. Use ticagrelor regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely. 13 aas11@aasraw.com

14. www.aasraw.com Stopping ticagrelor may increase your risk of a heart attack or stroke. Store at room temperature away from moisture and heat. (4) (4) What What should should I I avoid avoid while while taking taking ticagrelor(Brilinta)? ticagrelor(Brilinta)? Drinking alcohol while taking aspirin can increase your risk of stomach bleeding. Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth. While taking ticagrelor with aspirin, avoid using medicines for pain, fever, swelling, or cold/flu symptoms. They may contain ingredients similar to aspirin (such as salicylates, ibuprofen, ketoprofen, or naproxen). Taking certain products together can cause you to get too much aspirin which can increase your risk of bleeding. 8. Ticagrelor Side Effects WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly ticagrelor side effects when taking ticagrelor. Tell your doctor or get medical help right away if you have any of the 14 aas11@aasraw.com

15. www.aasraw.com following signs or symptoms that may be related to a very bad ticagrelor side effect: ♦ Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat. ♦ Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop. ♦ Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight. ♦ Very bad headache. ♦ Shortness of breath. ♦ Slow heartbeat. ♦ A heartbeat that does not feel normal. 15 aas11@aasraw.com

16. www.aasraw.com 9. What other drugs will affect ticagrelor? Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective. Tell your doctor about all your current medicines. Many drugs can interact with ticagrelor, especially: ♦ antifungal medicine; ♦ antiviral medicine to treat HIV or AIDS; ♦ a blood thinner; 16 aas11@aasraw.com

17. www.aasraw.com ♦ cholesterol medication; ♦ heart or blood pressure medication; ♦ opioid medication; ♦ seizure medicine; or ♦ tuberculosis medicine. 10. What should I know about storage and disposal of this medication? Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website for more information if you do not have access to a take-back program. 17 aas11@aasraw.com

18. www.aasraw.com It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. 11. What is the most important information I should know about ticagrelor (Brilinta)? Ticagrelor keeps your blood from coagulating (clotting) to prevent unwanted blood clots that can occur with certain heart or blood vessel conditions. Because of this drug action, ticagrelor can make it easier for you to bleed, 18 aas11@aasraw.com

19. www.aasraw.com even from a minor injury. Contact your doctor or seek emergency medical attention if you have bleeding that will not stop. You may also have bleeding on the inside of your body, such as in your stomach or intestines. Call your doctor at once if you have black or bloody stools, or if you cough up blood or vomit that looks like coffee grounds. These could be signs of bleeding in your digestive tract. While you are taking ticagrelor, do not take aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) without your doctor's advice. NSAIDs include ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Cataflam, Voltaren), indomethacin (Indocin), meloxicam (Mobic), and others. Ticagrelor may cause you to bleed more easily, especially if you have: a history of bleeding problems, surgery or a medical emergency, a disease affecting the blood vessels in your brain, a history of stomach or intestinal bleeding, or if you are 65 or older. Many drugs (including some over-the-counter medicines and herbal products) can interact with ticagrelor. It is very important to tell your doctor about all medicines you have recently used. Ask your doctor before taking any medicine for pain, arthritis, fever, or swelling. These medicines may affect 19 aas11@aasraw.com

20. www.aasraw.com blood clotting and may also increase your risk of stomach bleeding. Any doctor, dentist, surgeon, or other medical care provider who treats you should know that you are taking ticagrelor. 12. Where can I get more information? Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed. Every effort has been made to ensure that the information provided by AASraw up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. AASraw information has been compiled for use by healthcare practitioners and consumers in the United States and therefore AASraw does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. AASraw's drug information does not endorse drugs, diagnose patients or recommend therapy. AASraw's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and 20 aas11@aasraw.com

21. www.aasraw.com judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. AASraw does not assume any responsibility for any aspect of healthcare administered with the aid of information AASraw provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist. Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be 21 aas11@aasraw.com

22. www.aasraw.com accessed by clicking on this link. Join Platelet Aggregation Inhibitor Ticagrelor(274693-27-5) for sale--AASraw. 22 aas11@aasraw.com