Ticagrelor

Ticagrelor is a P2Y 12 platelet inhibitor indicated to reduce the risk of cardiovascular (CV) death, myocardial infarction (MI), 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. Ticagrelor tablets also reduces the risk of stent thrombosis in patients who have been stented for treatment of ACS. ( 1.1 ) to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events. While use is not limited to this setting, the efficacy of ticagrelor was established in a population with type 2 diabetes mellitus (T2DM). …

• ACS or History of MI Initiate treatment with 180 mg oral loading dose of ticagrelor tablets
• Then administer 90 mg twice daily during the first year
• After one year, administer 60 mg twice daily
• Patients with CAD and No Prior Stroke or MI Administer 60 mg ticagrelor tablets twice daily
• Acute Ischemic Stroke Initiate treatment with a 180 mg loading dose of ticagrelor tablets then continue with 90 mg twice daily for up to 30 days
• Use ticagrelor tablets with a daily maintenance dose of aspirin of 75 to 100 mg
• However, in patients who have undergone PCI, consider single antiplatelet therapy with ticagrelor tablets based on the evolving risk for thrombotic versusbleeding events
• General Instructions Advise patients who miss a dose of ticagrelor tablets to take their next dose at its scheduled time
• For patients who are unable to swallow tablets whole, ticagrelor tablets can be crushed, mixed with water, and drunk
• The mixture can also be administered via a nasogastric tube (CH8 or greater) [see Clinical Pharmacology ]
• Do not administer ticagrelor tablets with another oral P2Y 12 platelet inhibitor
• Avoid aspirin at doses higher than recommended [see Clinical Studies ]
• Acute Coronary Syndrome or a History of Myocardial Infarction Initiate treatment with a 180 mg loading dose of ticagrelor tablets
• Administer the first 90 mg maintenance dose of ticagrelor tablets, 6 to 12 hours after the loading dose

Ticagrelor tablets 90 mg is supplied as a round, biconvex, yellow, film-coated tablet debossed with ' ' (logo) on one side and T on the other side. Free from physical defects. Ticagrelor tablets 60 mg is supplied as a round, biconvex, white to off white, film-coated tablet debossed with “T” on one side and plain on the other side. Free from physical defects. • 60 mg and 90 mg tablets ( 3 )

• The safety and effectiveness of ticagrelor tablets have not been established
• In pediatric patients
• Pediatric use information describing a clinical study in which efficacy was not demonstrated is approved for AstraZeneca Pharmaceuticals LP’s BRILINTA® (ticagrelor) tablets
• However, due to AstraZeneca Pharmaceuticals LP’s marketing exclusivity rights, this drug product is not labeled with that information

About half of the patients in PLATO, PEGASUS, THEMIS and THALES were ≥65 years of age and at least 15% were ≥75 years of age. No overall differences in safety or effectiveness were observed between elderly and younger patients.

• Advise the patient to read the FDA-approved patient labeling (Medication Guide)
• Advise patients daily doses of aspirin should not exceed 100 mg and to avoid taking any other medications that contain aspirin
• Advise patients that they: • Will bleed and bruise more easily • Will take longer than usual to stop bleeding • Should report any unanticipated, prolonged or excessive bleeding, or blood in their stool or urine
• Advise patients to contact their doctor if they experience unexpected shortness of breath, especially if severe
• Advise patients to inform physicians and dentists that they are taking ticagrelor tablets before any surgery or dental procedure. …

• History of intracranial hemorrhage. • Active pathological bleeding. • Hypersensitivity to ticagrelor or any component of the product
• History of Intracranial Hemorrhage Ticagrelor tablets are contraindicated in patients with a history of intracranial hemorrhage (ICH) because of a high risk of recurrent ICH in this population [see Clinical Studies ,]. …

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. ( 7.1 , 7.2 ) • Opioids: Decreased exposure to ticagrelor. Consider use of parenteral anti-platelet agent. ( 7.3) • Patients receiving more than 40 mg per day of simvastatin or lovastatin or more than 20 mg per day of rosuvastatin may be at increased risk of statin-related adverse effects. ( 7.4 ) • Monitor digoxin levels with initiation of or any change in ticagrelor. ( 7.5 ) 7.1 Strong CYP3A Inhibitors Strong CYP3A inhibitors substantially increase ticagrelor exposure and so increase the risk of dyspnea, bleeding, and other adverse events. …

• Dyspnea was reported more frequently with ticagrelor than with control agents in clinical trials. Dyspnea from ticagrelor is self-limiting. ( 5.3 ) •Severe Hepatic Impairment: Likely increase in exposure to ticagrelor. ( 5.5 ) •Laboratory Test Interference: False negative platelet functional test results have been reported for Heparin Induced Thrombocytopenia (HIT). Ticagrelor is not expected to impact PF4 antibody testing for HIT. ( 5.7 ) 5.1 Risk of Bleeding Drugs that inhibit platelet function including ticagrelor increase the risk of bleeding [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6.1 )]. …

The following adverse reactions are also discussed elsewhere in the labeling: •Bleeding [see Warnings and Precautions ( 5.1 )] •Dyspnea [see Warnings and Precautions ( 5.3 )] Most common adverse reactions (>5%) are bleeding and dyspnea. ( 5.1 , 5.3 , 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088or www .fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. …

8.1 Pregnancy Risk Summary Available data from case reports with ticagrelor use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Ticagrelor given to pregnant rats and pregnant rabbits during organogenesis caused structural abnormalities in the offspring at maternal doses about 5 to 7 times the maximum recommended human dose (MRHD) based on body surface area. …

There is currently no known treatment to reverse the effects of ticagrelor tablets, and ticagrelor is not dialyzable. Treatment of overdose should follow local standard medical practice. Bleeding is the expected pharmacologic effect of overdosing. If bleeding occurs, appropriate supportive measures should be taken. Platelet transfusion did not reverse the antiplatelet effect of ticagrelor tablets in healthy volunteers and is unlikely to be of clinical benefit in patients with bleeding. …

تناولها عندما تتذكر، إلا إذا اقترب موعد الجرعة التالية. عندها تخطَّ الجرعة المنسية. لا تتناول جرعتين معًا أبدًا للتعويض. راجع النشرة، فبعض الأدوية مختلفة.