Ticagrelor

Ticagrelor 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).

Ticagrelor is a selective adenosine diphosphate (ADP) receptor antagonist acting on the P2Y12 ADP-receptor that can prevent ADP-mediated platelet activation and aggregation. Ticagrelor reversibly interacts with the platelet P2Y12 ADP-receptor.Ticagrelor does not interact with the ADP binding site itself, but interacts with platelet P2Y12 ADP-receptor to prevent signal transduction.Thus it prevents platelet activation & aggregation.

Ticagrelor treatment should be initiated with a single 180 mg loading dose (two tablets of 90 mg) and then continued at 90 mg twice daily. Patients taking Ticagrelor should also take aspirin daily, unless specifically contraindicated. Following an initial dose of aspirin (usually 325 mg), Ticagrelor should be used with a maintenance dose of aspirin of 75-100 mg. Maintenance dose of Aspirin above 100 mg decreased the efficacy of Ticagrelor. So, maintenance dose of aspirin above 100 mg should be avoided.

A patient who misses a dose of Ticagrelor should take only one 90 mg tablet (the next dose) at its scheduled time. Patients treated with Clopidogrel can be directly switched to Ticagrelor if needed. Switching from prasugrel to ticagrelor has not been investigated.

Treatment is recommended for up to 12 months unless discontinuation of Ticagrelor is clinically indicated. Ticagrelor can be administered with or without food.

CYP3A inhibitors: Avoid use of strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin).

CYP3A inducers: Avoid use with potent inducers of CYP3A (e.g., rifampin, dexamethasone, phenytoin,carbamazepine and phenobarbital).

Aspirin: Use of Ticagrelor with aspirin maintenance doses above 100 mg reduced the effectiveness ofTicagrelor.

Simvastatin, Lovastatin: Ticagrelor will result in higher serum concentrations of simvastatin and lovastatin because these drugs are metabolized by CYP3A4. Avoid simvastatin and lovastatin doses greater than 40 mg.

Digoxin: Because of inhibition of the P-glycoprotein transporter, monitor digoxin levels with initiation of or any change in ticagrelor therapy.

Other Concomitant Therapy: Ticagrelor can be administered with unfractionated or low-molecular-weight heparin, GPIIb/llla inhibitors, proton pump inhibitors, beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers.

Ticagrelor is contraindicated in case of-

• Hypersensitivity to Ticagrelor or to any of the excipients
• Active pathological bleeding (peptic ulcer)
• History of intracranial haemorrhage
• Moderate to severe hepatic impairment
• Co-administration of Ticagrelor with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir)

Dyspnea,bleeding,headache,cough,dizziness,nausea,atrial fibrillation, hypertension, non-cardiac chest pain, diarrhea, back pain, hypotension, fatigue, chest pain.

Pregnancy category C. There are no or limited amount of data from the use of Ticagrelor in pregnant women.Ticagrelor is not recommended during pregnancy.

Nursing mothers: Available pharmacodynamic/toxicological data in animals have shown excretion of Ticagrelor and its active metabolites in milk. A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from ticagrelor therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the women.

General Risk of Bleeding: Drugs that inhibit platelet function including Ticagrelor increase the risk of bleeding.

Concomitant Aspirin Maintenance Dose: Use of Ticagrelor with maintenance doses of aspirin above 100 mg decreased the effectiveness of Ticagrelor. Therefore, after the initial loading dose of aspirin (usually 325 mg), use Ticagrelor with a maintenance dose of aspirin of 75-100 mg.

Moderate Hepatic Impairment: Ticagrelor has not been studied in patients with moderate hepatic impairment.

Discontinuation of Ticagrelor: Discontinuation of Ticagrelor will increase the risk of myocardial infarction, stent thrombosis, and death.

There is currently no known antidote to reverse the effects ofTicagrelor and it is not expected to be dialysable.Treatment of overdose should follow local standard medical practice.The expected effect of excessive ticagrelor dosing is prolonged duration of bleeding risk associated with platelet inhibition. If bleeding occurs appropriate supportive measures should be taken.

Anti-platelet drugs

Pediatric Use: The safety and effectiveness of Ticagrelor in pediatric patients have not been established.

Geriatric Use: No overall differences in safety or effectiveness were observed in geriatric patients.

Hepatic Impairment: Ticagrelor has not been studied in the patients with moderate or severe hepatic impairment. Ticagrelor is metabolized by the liver and impaired hepatic function can increase risks for bleeding and other adverse events. Hence,

Renal Impairment: No dosage adjustment is needed in patients with renal impairment. Patients receiving dialysis have not been studied.

Protect from light & moisture. Store below 25° C. Keep out of reach of children.